KR102146154B1 - Diagnosis kit with transparent detection areas divided by grids and optical scanning reader using the same - Google Patents

Abstract

Disclosed are a diagnostic kit having a grid-divided transparent substrate capable of improving the detection sensitivity of the diagnostic kit, and an optical diagnostic device using the same. The diagnostic kit is a diagnostic kit using immunochromatography technology, and includes a sample pad, a bonding pad, a detection pad, and an absorption pad connected in the order described from one side to the other on one side of the transparent film substrate, and the space inside the detection pad A stripe-shaped opaque pattern is disposed on the film substrate corresponding to the test area of.

Description

DIAGNOSIS KIT WITH TRANSPARENT DETECTION AREAS DIVIDED BY GRIDS AND OPTICAL SCANNING READER USING THE SAME}

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

Diagnostic kits are developed using lateral flow tests of membrane materials such as paper or fiber or immunochromatography technology, and are used as in vitro diagnostic medicines for point of care tests (POCT), not for laboratory use. The field test refers to a test that can be used for diagnosis and treatment by quickly performing a test sample such as centrifugation in the vicinity of a subject without pre-treatment or through a simple pre-treatment process. The diagnostic kit is also called a rapid diagnostic kit.

Immunochromatography technology uses insoluble carrier particles to which a ligand that characteristically recognizes the substance to be detected is used to capture the substance to be detected, moves it by using the capillary phenomenon of the membrane, and is fixed to a predetermined position in the specimen. It is one of the immunological techniques for analyzing the presence or absence of a substance to be detected using insoluble carrier particles that aggregate at other predetermined positions in a test piece by allowing it to bind with a capture substance that specifically binds to a detection substance.

In general, the examination of the diagnostic results of the rapid diagnostic kit is based on physical detection results such as the concentration and mass of the antibody captured in the capture line or test line after the sample has passed through the detection pad or membrane. It is achieved by acquiring an optical signal in an image or an electrical signal converted from it, and analyzing the signal.

Existing rapid diagnostic kits that apply optical detection rather than visual detection do not analyze all areas of the trapped substance or antibody in the area of the test line, but a virtual rectangular area of a specific size for the area to which the optical beam is irradiated. In-hollow or window areas are examined, diagnosed, and read.

On the other hand, in the conventional rapid diagnosis kit, the rectangular hollow is ideally distributed evenly within the horizontal and vertical hollow regions of a certain size, and the detection pad area in the kit is uniformly distributed and has a uniform velocity. Accurate inspection, diagnosis, and reading are possible, assuming they pass through and are evenly integrated in the hollow area. However, in reality, there are various factors of variation in kit manufacturing, and the state of the sample itself is not completely homogeneous, so in fact, the existing rapid diagnosis kit often shows uneven and irregular test results.

As such, it is very difficult to detect minute changes in the overall aspect of the hollow by inspecting the overall condition of the entire hollow occupying a relatively large area even if there is no special irregularity in the existing rapid diagnosis kit.

Accordingly, the present invention can solve the problem of detection reliability due to mechanical errors of the membrane, fabrication deviations of the square pattern, etc. in the existing diagnostic kit using the rectangular hollow region, and the problem of irregular detection signals due to such errors or deviations. It is an object of the present invention to provide a diagnostic kit having a grid-divided transparent substrate and an optical diagnostic device using the same. That is, an object of the present invention is to provide a diagnostic kit having a grid-divided transparent substrate capable of improving the reliability and stability of a device by changing a two-dimensional rectangular hollow pattern into a one-dimensional grid, and an optical diagnostic device using the same.

Another object of the present invention is to increase the accuracy of diagnosis even when the concentration of a detection object of a sample for diagnosis is low, the absolute amount is insufficient at the beginning of the disease, or the concentration is decreased due to dilution by a reaction solution. It is to provide a diagnostic kit having a divided transparent substrate and a method of manufacturing the same.

Another object of the present invention is that it is possible to accurately and accurately diagnose a diagnosis result in a quantitative diagnosis, to accurately capture a small change in state between a plurality of specimens in a state with various mutation factors, and to effectively derive a quantitative result. It is to provide a diagnostic kit having a grid-divided transparent substrate, a method of manufacturing a diagnostic kit, an optical diagnostic device 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 immunochromatography technology, which is a sample pad connected in the order described from one side to the other on one side of a transparent film substrate, and a bonding pad ( A conjugate pad, a detection pad, and an absorbent pad are provided, and a stripe-shaped opaque pattern is disposed on the film substrate corresponding to a test area in the form of a space in the detection pad. .

In one embodiment, a direction in which each line pattern extends in the opaque pattern may be orthogonal to a direction in which the coupling pad and the detection pad are connected to extend, or a direction in which the detection pad and the absorbing pad are connected to extend. .

In one embodiment, in the opaque pattern, each line pattern is inclined at a specific angle of 45° or less from a direction in which the coupling pad and the detection pad are connected to extend, or a direction in which the detection pad and the absorbing pad are connected to extend. It can be extended to correspond to the orientation of the picture.

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

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

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

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

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

In one embodiment, the diagnostic kit may further include a case for accommodating a pad assembly comprising the film substrate, the sample pad, the bonding pad, the detection pad, and the absorption pad. The case may include a sample inlet corresponding to the sample pad and an opening corresponding to the test area, and the opening may expose the test area and a control area on the detection pad to the outside.

In order to solve the above technical problem, a method of manufacturing a diagnostic kit according to another aspect of the present invention includes: arranging stripe-shaped opaque line patterns in a partial region of a transparent 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 absorbent 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 a connection between the coupling pad and the detection pad. An extension direction or a direction perpendicular to a direction in which the detection pad and the absorption pad are connected to each other, or each line pattern in the opaque pattern is a direction in which the bonding pad and the detection pad are connected to each other to extend, or the detection pad and the absorption pad It is configured to extend in correspondence with the direction in which the pads are connected and inclined at a specific angle of 45° or less.

In order to solve the above technical problem, an optical diagnostic device according to another aspect of the present invention is an optical diagnostic device using a diagnostic kit, comprising: a light-emitting device emitting light to a signal detection unit in a test area of the diagnostic kit; A light-receiving element for detecting a change in the amount of light between the striped line patterns of the signal detector by the incident light when incident light of a single wavelength from the light-emitting element is focused on the signal detector of the diagnostic kit; An actuator coupled to the light receiving element to control focusing of the light receiving element; And a driving unit for moving a relative position between the light-emitting element and the light-receiving element, and the diagnostic kit, and scanning in a direction crossing the line patterns of the signal detection unit by the operation of the driving unit.

In one embodiment, the optical diagnosis device includes 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 it may further include a filter attached to the front end of the lens.

In one embodiment, the optical diagnosis device 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 may be connected to other components of the optical diagnostic device through a wired cable or a wireless network.

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

In one embodiment, the analysis unit is a matrix (m*) for a decomposition section consisting of a row (n) in the intersecting direction (y) and a direction (x) orthogonal to the intersecting direction (m). A two-dimensional memory array of n matrix) is created, and the voltage (V) of the signal detected by the light-receiving element is stored in A[n][m] in correspondence with the matrix-where the 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 the x with respect to the i-th (y[i]) of the y A voltage one-dimensional memory array (B[n]) for storing the summation is generated, and voltages for the x[0] to x[m-1] for the y[i] are summed, and a specific memory array B[ j]), and summing the voltages for x[0] to x[m-1] for [0] to [n-1] of y, respectively, to a specific memory array (B[j]) It may be stored, and the detection sensitivity (Ii) is calculated by dividing each B[j] by the corresponding area (Si), and the maximum detection sensitivity value is selected as the effective determination reference value.

In one embodiment, the analysis unit may be configured to adjust the saturation and background levels according to the sample reaction or the concentration of the sample by setting the maximum and minimum of the standard sample for each antibody, and adjusting a gain for this.

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

According to the above-described diagnostic kit having a grid-divided transparent substrate, the manufacturing method of the diagnostic kit, and the optical diagnostic device using the diagnostic kit, the mechanical error of the membrane (bonding pad) or the signal detection unit within the membrane in the diagnostic kit, It is possible to effectively solve a problem of reliability of detection due to fabrication deviations of a square pattern, and a problem in which a detection signal is irregularly generated due to such errors or deviations. That is, the reliability and stability of a diagnostic kit and an optical diagnostic device using the same can be greatly improved by changing a two-dimensional rectangular hollow pattern to a one-dimensional grid.

In addition, according to the present invention, accuracy and reliability of diagnosis can be ensured even when the concentration of the detection target of the specimen for diagnosis is low, the absolute amount is insufficient at the beginning of the disease, or the concentration is decreased due to dilution by the reaction solution. There is an advantage to be able to.

In addition, according to the present invention, it is possible to accurately and precisely diagnose the diagnosis result in quantitative diagnosis, and to accurately capture small state changes between multiple specimens in a state with various mutation factors, and to effectively derive quantitative results. 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. 1.
3 is a partial exploded perspective view for explaining the assembly structure of the diagnostic kit of FIG. 1.
4 to 6 are diagrams for explaining another embodiment of the opaque grid of the diagnostic kit of FIG. 1.
7 is a partially enlarged plan view of a structure of an opaque grid for a signal detection unit of the diagnostic kit of the present embodiment.
8 is a cross-sectional view for explaining 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.
FIG. 10 is a diagram for explaining an operating principle of an optical diagnostic device using the diagnostic kit of FIG. 9.
11 is a diagram for explaining the operating principle of a diagnostic kit including a signal detection unit according to the present embodiment.
12 is a diagram illustrating signal waveforms detected by the diagnostic kit equipped with the signal detection unit of FIG. 11.
13 is a diagram illustrating an operating principle of a diagnostic kit including a signal detection unit according to a comparative example.
14 is a perspective view of an optical diagnostic device according to another embodiment of the present invention.
15 is a perspective view of a detection optical system of the optical diagnosis device of FIG. 14.
16 is a perspective view from another side of the detection optical system of the optical diagnostic device of FIG. 14.
FIG. 17 is a diagram for explaining an operating principle of the optical diagnosis device of FIG. 14.
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 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 a transparent or transparent property. I can.

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.

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 are provided.

In more detail, the substrate 110 may be referred to as a base, a base substrate, a transparent substrate, and 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 this embodiment, an opaque grid 112a for forming a detection unit or a signal detection unit 112 is disposed on the substrate 110. The opaque grid 112a is formed in a linear stripe pattern extending in one direction or in a y-direction. The signal detection unit 112 may include an empty space portion 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 may have the same separation distance as other adjacent line patterns. In addition, the width and separation distance of each line pattern in the signal detection unit 112 may be the same. Using such a pattern structure, it is possible to greatly increase analysis speed and performance by simplifying signal analysis when detecting an optical signal.

The width of each line pattern in the signal detection unit 112 may be 80 µm to 120 µm, and an interval between adjacent line patterns may be 80 µm to 120 µm. The width and the spacing may be the same, but are not limited thereto. These widths and intervals may have a difference in size according to the size of a substance to be detected, such as a protein to be detected.

The membrane 120 includes a test line made of an antibody that captures a sample and a control line indicating whether the experiment was normally performed. The inspection line corresponds to the test line or the signal detection unit 112 (see FIGS. 8 and 9). In this embodiment, the membrane 120 has a space portion 120e at an intermediate portion thereof in the longitudinal direction. The space part 120e functions as a part of the signal detection part 112 disposed to detect a desired signal by using the light transmittance of the biomarker captured on the membrane 120.

The space portion 120e may correspond to a portion in which the membrane is not disposed in the middle portion of the membrane 120. The width L4 of the space portion 120e may be about 1 mm. The space 120e is installed to expose at least a part of the opaque grid partially disposed on the lower 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 the opaque pattern can be formed on a part of the substrate 110. The opaque grid refers to the same object as a unidirectional grid, a opaque pattern, and the like, and is used interchangeably in this specification.

Meanwhile, depending on implementation, the space 120e may have a size of 1 mm or less or may not be spatially configured according to the optical characteristics of the sample. That is, the length L4 of the space portion 120e may be 0 (zero). When the space is not installed, the concentration of the sample can 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 the material to be analyzed from various existing reverse osmosis membranes, nanofiltration membranes, ultrafiltration membranes, microfiltration membranes, etc., for example, a nitrocellulose (NC) membrane or a polyvinylidene fluoride (PVDF) membrane. The membrane 120 is attached or fixed on the substrate 110 by an adhesive 170 or the like, and has a second length L2 smaller than that of the substrate 110 in the y-direction or longitudinal direction, and will be referred to as a detection pad or the like. I can.

The conjugate pad 130 contains 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 an upper end of one side of the membrane 120, and the other end of the bonding pad 130 opposite to the one end may be in close contact with or attached to a lower end of one side of the sample pad 150 .

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

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

The sample pad 150 is a part to which a sample to be detected is supplied from the outside. The sample pad 150 may have a pre-processed state by a buffer reagent or the like. The sample pad 150 may be superimposed on one end of the bonding 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 portion 120e of the membrane 120 or may be disposed to cover the entire exposed upper portion of the membrane 120 including the space portion 120e. The exposed upper portion may correspond to a constant surface of a portion of the membrane 120 positioned between the bonding 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 detection unit 112.

3 is a partial exploded perspective view for explaining the assembly structure of the diagnostic kit of FIG. 1.

2 and 3, the diagnostic kit according to the present exemplary embodiment may have a printing structure for making a transparent substrate detection unit and a laminated structure between components constituting the diagnostic kit.

First, an opaque grid 112a for forming a detection unit, that is, a signal detection unit 120, is formed in a partial area of the transparent substrate 110. The opaque grid 112a corresponds to linear stripe-shaped line patterns or unidirectional grids extending straight in the length direction or y-direction of the substrate 110.

The unidirectional grid may be disposed on the lower 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, a grid is formed on the opposite surface of the test line disposed on the transparent film substrate where the sample flows, so that the flow of the sample may not be affected.

Next, the membrane 120 is disposed on the upper surface opposite to the lower surface of the substrate 110. The membrane 120 may be fixed on the substrate 110 by an adhesive or other adhesive 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 of the bonding pad 130 is attached to an upper end of the membrane 120 in the longitudinal direction or the y-direction of the membrane 120, and the sample pad 150 is disposed on the other end of the bonding pad 130. Place one end of ). In addition, one end of the absorbent pad 140 is disposed above the other end of the membrane 120.

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

The size of the surface shape (a portion forming the surface) of the second adhesive is smaller than an area of a junction between the membrane 120 and the bonding pad 130 and smaller than an area of a junction between the membrane 120 and the absorbent pad 140. This is a flow path at the interface between the components so that antigens, insoluble carrier particles, or a combination thereof can properly move from the sample pad 150 to the absorbent pad 140 through the membrane 120, which is a porous fibrous, by a capillary shape. It is flexible to secure as wide or diverse as possible.

If the opaque grid of the stripe pattern described above is used, in particular, the width of each line pattern of the opaque grid is formed equal, the spacing between adjacent line patterns is formed equal, or between the width of each line pattern and adjacent line patterns. When the interval is formed equally, different signal analysis results are generated according to the slope between the signal detection unit 112 and the scanning direction of the laser light (see the x-direction in Fig. 8) when the diagnostic kit is placed on the optical diagnostic device and analyzed. In addition to effectively solving the problems in the existing structure, it can greatly improve the stability and reliability of the analysis speed and performance.

4 to 6 are diagrams for explaining another embodiment of the opaque grid of the diagnostic kit of FIG. 1. 7 is a partially enlarged plan view of a structure of an opaque grid for a signal detection unit of the diagnostic kit of the present embodiment.

In the diagnostic kit according to the present embodiment, the signal detection unit 112 may have various shapes other than a structure disposed on the lower surface of the substrate 110 (see FIG. 3 ). Here, the upper surface opposite to the lower surface of the substrate 110 becomes a space portion (120e in 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 illustrated in FIG. 4. The height of the printed structure of the opaque grid 112a may be adjusted according to the amount of the antibody to be captured and the optical characteristics of the absorbance detected accordingly.

In addition, the opaque grid 112a may be buried in the upper surface of the substrate 110 as shown in FIG. 5 and one surface may be exposed on the upper surface 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 a lower surface opposite to the upper surface of the substrate 110 according to implementation.

In another embodiment, the opaque grid 112a may be installed so as not to be exposed to the upper and lower surfaces while being installed between the upper and lower surfaces of the substrate 110 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. Both the first transparent film and the second transparent film may be pressed flat on both sides in a single film form.

Meanwhile, the opaque grid 112a employed in this embodiment is not limited to the above-described embodiment, and may include a structure in which an opaque grid is arranged as a separate film on the film substrate. The thickness of the opaque grid 112a protruding from the substrate 110 or installed by being coupled to the substrate 110 may be relatively small compared to the width, and may be, for example, a size of several tens of μm or less.

In the above-described embodiments, the opaque grid 112a extends in the longitudinal direction or y-direction in which each line pattern in the pattern extends, such as a diagnostic kit or a membrane of the diagnostic kit, as shown in FIG. 7. The main feature may be that the width w and the spacing d between adjacent line patterns are the same. In a specific embodiment, the above-described width (w) and spacing (d) may be equal to each other by 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.

In addition to the effect of improving the analysis speed and the analysis performance, the opaque grid having such a fine structure has the advantage of greatly improving the detection sensitivity by increasing the detection density that can be calculated in the same area.

For example, in the case of having a test line to which the grid is not applied, the particle density is a value obtained by dividing the number of particles in the total area by the total area. On the other hand, in a stripe-shaped opaque pattern, i.e., a unidirectional grid, 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 be greatly improved.

8 is a cross-sectional view for explaining 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 film-based substrate 110, a membrane 120 corresponding to a detection pad, a bonding pad 130, an absorption pad 140, and a sample pad 150. The pad assembly may be formed in any one of the embodiments described above with reference to FIGS. 1 to 7.

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

The line patterns constituting the opaque grid or the opaque grid of the signal detection unit disposed on the substrate 110 are roughly parallel to the flow direction of the fluid or object in the diagnostic kit and are spaced apart from each other in the width direction by a light-blocking or opaque stripe ( stripe) shape. Here, the direction in which the fluid flows may be the same direction as the direction in which each line pattern of the stripe pattern of the opaque grid extends. The flow direction of this fluid may be a direction orthogonal to the direction (x-direction) in which the laser light moves when irradiating the laser light (Li) to the diagnostic kit, or a direction that intersects the direction perpendicular to the direction at about 45° or less. 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 a test area or test line corresponding to the signal detection unit 112 and a control area or control line 114 on the detection pad of the membrane 120 to the outside. The control line 114 is provided with a predetermined antigen, etc., and is used to check whether the specimen is an appropriate and meaningful object, such as saliva, blood, urine, etc. of the human body.

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

FIG. 10 is a diagram for explaining an operating principle of an optical diagnostic device using the diagnostic kit of FIG. 9.

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, for convenience of illustration, the opaque grid 112a of the signal detection unit 112 is enlarged and shown.

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

An objective lens 244 is disposed between the laser 241 and the diagnostic kit 100 to focus incident light of a single wavelength onto the transparent substrate. In addition, the change in the amount of light in the transparent portion between each grid pattern of the opaque grid 112a may be focused to 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 controlled by focusing through a driving unit 284 such as a variable charge motion (VCM) actuator, if necessary. The driving unit 284 may be coupled to the housing 283 supporting the photodiode 280 and the sensor lens 282. In addition, the change in the amount of light in the grid pattern in the signal detection unit 112 may detect a signal to be analyzed for the entire area of the signal detection unit 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 detection unit is arranged to extend in the first direction along the y-axis orthogonal to the x-axis. 1 Even when it is inclined to a predetermined angle with the direction, i.e., regardless of the manufacturing process or the operator's handling method of the diagnostic kit, it is possible to substantially always perform stable signal detection, thereby obtaining a fast and reliable analysis target signal can do.

11 is a diagram for explaining the principle of operation of a diagnostic kit including a signal detection unit according to the present embodiment. 12 is a diagram illustrating signal waveforms detected by the diagnostic kit equipped with the signal detection unit 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 diagnosis apparatus irradiates a laser beam to a signal detection unit of the above-described diagnostic kit, and scans a change in the amount of light at the signal detection unit. The scanning direction Sd1 may be an x-direction that is orthogonal to a y-direction that 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 changes and differences in the transparent film portion and the printed portion (opaque grid portion). The condensed beam spot p1 may be formed on the signal detection unit 112 of the diagnostic kit by the laser beam. In FIG. 11, four are shown at an arbitrary point for size comparison with a fine pattern, etc., in fact, only one beam spot p1 may be formed near a focal point of a laser beam moving along the scan 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 comparative configuration (see FIG. 13) that the x-axis grid and the y-axis grid must vertically intersect in order to secure reliability. . That is, in this embodiment, as shown in (a) and (b) of Fig. 11, by using the signal detection unit 112 having an opaque grid 112a, it is not necessary to arrange the x-axis grid and the y-axis grid There is no need to vertically intersect, and even when a manufacturing error occurs in the opaque grid 112a, signal detection and analysis can be performed substantially stably.

The manufacturing error may include a case where the extension direction of the line patterns in the opaque grid 112a is inclined at a predetermined angle with the length direction or y-direction of the diagnostic kit. In addition, the manufacturing error may include a case where a deviation occurs in the width of each line pattern in the opaque grid, and the width of the line pattern and the spacing 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 in a form inclined at an arbitrary angle in the y-direction and y1-direction, as shown in FIG. 11(b). The inner angle of the y-direction and the y1-direction may be 45 degrees or less. Even in this case, according to the diagnostic kit according to the present embodiment, the analysis speed and analysis performance can be maintained.

That is, when a signal is detected from the diagnostic kit through the optical analysis device, the opaque grid or the diagnostic kit is determined for the scan direction (Sd1) of the laser diode due to manufacturing errors, mechanical errors, and the operator's working mode or mistakes. Even if it is placed in a state rotated by an angle (see Fig. 11(b)), as shown in Fig. 12, the signal waveform s1 in the section corresponding to the opaque grid always appears at a constant size and interval as a reference voltage. On the basis of this, the signal waveform can be effectively analyzed.

Here, the level of the reference voltage may be set to a desired voltage (voltage, vol.) by a user. In addition, a predetermined section of the waveform appearing in the detection signal according to the reference voltage, that is, a 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, but the length of each section is substantially the same.

Moreover, even if a mechanical error of a detector device including a light emitting device or a light receiving device occurs, the reference voltage of the signal detection section corresponding to the opaque grid always appears at a certain size and interval, thus limiting the mechanical error of the detector. You can overcome it effectively.

In addition, a line area other than the opaque grid of the signal detector 112 is a transmissive area and may represent a signal waveform having a voltage level different from that of the reference voltage. In particular, the signal waveform or the detection signal s2 in the light-transmitting area may exhibit different levels or waveforms according to the concentration of a sample, sample, specimen, or precipitate captured in the light-transmitting area. The detection signal s2 may have a predetermined voltage V or peak to peak as a difference between the minimum voltage and the maximum voltage. As described above, according to this embodiment, in the diagnostic kit with the convenience of sample processing in the diagnostic kit using peak-to-peak values, etc., in the diagnostic kit with high performance and economy, accurate quantitative analysis taking into account the noise of the result and maximizing user convenience while maximizing the analysis result. There is an advantage that can greatly improve the reliability of the product.

13 is a diagram illustrating an operating principle of a diagnostic kit including a signal detection unit according to a comparative example.

This comparative example will be described focusing on a problem occurring in a diagnostic kit to which a bidirectional grid (square pattern) is applied.

As shown in (a) of FIG. 13, if a manufacturing error occurs in a bidirectional grid (rectangular 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. Thereby, irregularities may appear in the detection signal. In particular, when attaching a bidirectional grid to a diagnostic kit, it may be considered that the bidirectional grid is often rotated and attached due to manufacturing errors.

Further, in the case of the comparative example, scanning in the x-direction or the y-direction may not be constant due to a mechanical error of the detector. That is, when the y-direction is not correctly orthogonal to the scan direction (Sd1) of the laser beam (see Fig. 13(b)), physical detection results such as concentration and mass of the antibody captured in the test line When acquiring an optical signal including an image of an image or an electrical signal converted therefrom and analyzing the acquired signal, the acquired signal appears differently according to the arrangement error of the signal detection unit, which greatly reduces the reliability of the analysis result. .

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

As described above, in the comparative example, errors in detection signals due to manufacturing errors, mechanical errors, handling deviations, and the like, and analysis accuracy and reliability according to the errors may occur.

On the other hand, in another comparative example, the width of the line pattern of the opaque grid may be configured to be smaller than the spacing between adjacent line patterns, or differently, but even in that case, if the scan direction and the pattern direction are not almost accurately aligned, one Since the laser point p1 of is transmitted through the signal detection unit 112 and the accuracy of the division of the grid boundary is lowered in the signal detected, it is difficult to interpret the transparent section and the opaque section.

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

Referring to FIG. 14, the optical diagnosis apparatus 200 according to the present 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 A motor 260 and a connection terminal 270 are provided. The detection optical system 240 includes a laser diode, and the photodiode may be disposed under 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 worktable 230 may be provided with an uneven portion or protrusion for fixing or supporting the diagnostic kit as a diagnostic kit or a placement portion. 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 that electrically connects the laser diode, the photodiode, the first motor 250 and the second motor 260 to a control system to be 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 includes a laser diode 241, a plurality of mirrors 242 and 245, a filter 243, a collimator lens, as shown in FIGS. 15 and 16. 244) and a housing 246 may be provided. On one side of the housing 246, the first shaft and the first shaft can 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. A coupling portion 247 coupled to the second shaft may be provided.

The laser diode 241 can irradiate a laser beam with a wavelength of 405 nm, 650 nm or 780 nm. The filter 243 is installed at the front end of the collimator lens 244 and functions to adjust the amount of light of the laser beam to a desired level or a preset level by the user. The filter 243 may operate to block wavelengths other than a specific wavelength, such as a 405 nm wavelength.

The collometric lens 244 functions to condense the laser beam whose light amount is adjusted through the filter 243 to the signal detection unit 112. The plurality of mirrors 242 and 245 may be used to change the traveling direction of the laser beam.

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

In addition, a filter 243 is attached to the front end of the collimator lens 244 in which light is condensed to adjust the laser light amount, and the light is adjusted to a desired level, and the transmission type diagnostic kit 100 The light transmitted from the test surface, which is the signal detection unit 112 of, may detect a signal through an integrated circuit (PDIC) of a photodiode.

The distance d6 from the reflection 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 condensing lens 282 is 0.9 mm, the thickness d2 of the condensing lens 282 on the optical path is 1.9 mm, and the condensing 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 between the emission filter 283 and the test surface of the transmission type 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 may be performed by using a laser of a specific wavelength to measure the black intensity of light at a corresponding wavelength. In this case, the laser is operated to continuously irradiate light in the form of a pulse, the intensity of the laser beam is adjusted through the filter 243, and the house may be focused with the collimator lens 244.

Specifically, in signal detection, since light cannot pass 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, and the material reaction If even a part of this occurs, only a part of the irradiated light is transmitted, and therefore, when the transmitted light between the grid division sections is collected by the photodiode, the voltage change can be checked and quantified to detect the presence or absence of a signal (see FIG. 12).

For example, the absorption voltage of distilled water is 1.41V, the absorption voltage for the first mixture of a first concentration (1/40) obtained by mixing a predetermined material in distilled water at a first content is 1.82V, and the same material is added to distilled water. The 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) in which the same material is mixed in distilled water with the third content The absorption voltage for is 2.48V. In this embodiment, the sensitivity and characteristics of the detection signal according to the concentration change of the sample can be accurately, quickly and reliably analyzed based on the difference in the absorption 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), the laser of the optical diagnosis apparatus 200 described above with reference to FIG. It may be connected to the diode LD, 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 both input and output such as a touch liquid crystal display (Touch LCD).

The main control unit 293 may operate to extract the data of the photodiode at regular intervals by decomposing the unit reference signal in 4096 steps at, for example, 12-bit resolution. In addition, the main control unit 293 sets the 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 this configuration, it is possible to greatly improve the conversion speed in the analog digital conversion system compared to the control unit of 4 bit or 8 bit resolution.

The main control unit 293 may be referred to as a control unit, a control unit, a central processing unit, and 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 acquiring 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, photodiode (PD) detection voltage accumulation and analysis algorithm, and the like.

The scanning schedule algorithm is a first step of driving to form an autofocus array 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-where 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 moving a small section in the y-axis direction, wherein, when the micro section is moved, the autofocus array formed in the first step is used; The fifth step may be applied continuously to complete the scan from the x-axis origin to the end point and return to the x-axis origin.

In addition, 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 a y-axis direction as a row (n) and an x-axis direction as a column (m). a first step of generating [m]; The second step of storing the voltage (V) of the signal detected by the photodiode or the light-receiving device after scanning and light irradiation in a specific memory area of the two-dimensional memory array A[n][m]- Here, 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 sum of voltages 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 ]); A fourth step of summing the voltages for x[0] to x[m-1] for y[i] and storing them in a specific one-dimensional memory array B[j]; As a step of repeating the fourth step, a specific one-dimensional memory array (B[j]) by summing voltages for the x[0] to x[m-1] with respect to the y-axis [0] to [n-1] A fifth step of storing each in; A sixth step of calculating detection sensitivity (Ii) by dividing each B[j] by a corresponding area (Si); And a series of processes of the 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, each count detection sensitivity can be calculated by the following equation (2).

According to the present embodiment, a new optical diagnostic device having excellent sensitivity and specificity classification performance can be provided by evaluating the difference in photodiode voltage between the transparent section and the opaque section using a diagnostic kit having a grid-divided transparent substrate.

Meanwhile, the above-described control system 290 may have a form coupled to the base plate or support frame of the optical diagnosis apparatus described above with reference to FIG. 14, depending on the implementation, and vice versa. That is, the optical diagnosis apparatus described above with reference to FIG. 14 may be implemented in a form integrally coupled to the housing or case of the control system described with reference to FIG. 18.

Claims (13)

As a diagnostic kit using immunochromatography technology,
A sample pad, a conjugate pad, a detection pad, and an absorbent pad are provided on one surface of the transparent film substrate in the order described from one side to the other,
A diagnostic kit in which a one-dimensional linear stripe-shaped opaque pattern is disposed on the film substrate corresponding to a test area in the form of a space in the detection pad. The method according to claim 1,
A diagnostic kit in which a direction in which each line pattern extends in the opaque pattern is orthogonal to a direction in which the coupling pad and the detection pad are connected to extend, or a direction in which the detection pad and the absorbing pad are connected and extended. The method according to claim 1,
In the opaque pattern, each line pattern corresponds to a direction in which the coupling pad and the detection pad are connected and extended, or a direction in which the detection pad and the absorbing pad are connected and extended, and a direction inclined at a specific angle of 45° or less. Extended diagnostic kit. The method according to claim 1,
In the opaque pattern, the width of the first line pattern and the distance between the second line pattern adjacent to the first line pattern are the same. The method according to claim 1,
In the opaque pattern, a width of each line pattern and an interval between adjacent line patterns are the same. The method according to claim 1,
The opaque pattern is disposed on the one surface of the film substrate, on the other surface that is opposite to the one surface, or is disposed between the one surface and the other surface. The method of claim 6,
The opaque pattern is a diagnostic kit that is buried so that its surface is exposed on the one side or the other side of the film substrate. The method according to claim 1,
A diagnostic kit further comprising a light-transmitting protective film covering the detection pad and the test area. The method according to claim 1,
The film substrate, the sample pad, the bonding pad, further comprising a case for accommodating a pad assembly consisting of 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 area,
The opening is a diagnostic kit for exposing the test area and the control area on the detection pad to the outside. As an optical diagnostic device using a diagnostic kit,
A light emitting device that emits light to a signal detection unit in a test area of the diagnostic kit;
When the incident light of a single wavelength from the light emitting device is focused on the signal detection unit of the diagnostic kit, a change in the amount of light between the opaque line patterns of the one-dimensional straight stripe shape of the signal detection unit by the incident light is detected. Light-receiving element;
An actuator coupled to the light receiving element to control focusing of the light receiving element; And
And a driving unit for moving a relative position between the light emitting device and the light receiving device and the diagnostic kit,
An optical diagnostic device that scans in a direction crossing the line patterns of the signal detection unit by the operation of the driving unit. The method of claim 10,
A lens disposed at the front end of the light emitting device to condense light to control the amount of light of the light emitting device; And a filter attached to the front end of the lens. The method of claim 10,
Further comprising a control unit for controlling the operation of the light emitting device, the light receiving device, the actuator, and the driving unit. The method of claim 12,
The control unit is a two-dimensional matrix (m*n matrix) for a decomposition section in which the crossing direction (y) is a row (n) and a direction (x) orthogonal to the crossing direction is a column (m). A memory array is created, and the voltage (V) of the signal detected by the light-receiving element corresponding to the matrix is stored in a specific memory area A[n][m]-here, a group of an opaque section corresponding to the line patterns Low voltage is set to 0 or a predetermined voltage-The sum of the voltages 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 storage is generated, and voltages for the x[0] to x[m-1] for the y[i] are summed to provide a specific memory array B[j] ), and summing the voltages for x[0] to x[m-1] for [0] to [n-1] of y, and storing each in a specific memory array (B[j]) , The detection sensitivity (Ii) is calculated by dividing each B[j] by a corresponding area (Si), and a maximum value of detection sensitivity is selected as an effective determination reference value.

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