KR20130117301A - Lateral flow device and method for analyzing sample - Google Patents

Abstract

PURPOSE: A lateral flow analyzer is provided to largely improve detection sensitivity of an analyte which is tagged with a fluorescent material. CONSTITUTION: A lateral flow analyzer (1) comprises: a sample inlet part (210) for putting a sample; a flow path (320) which is connected to the sample inlet part and has a space in which the sample flows in/out; a photonic crystal (102) formed at a part of the inside of the flow path; and receiving elements which are fixed at a part of the inside of the flow path and are specifically conjugated with an analyte. A method for detecting an analyte comprises the steps of: putting a sample into the sample inlet part; conjugating an analyte contained in the sample with a fluorescent material; and binding the conjugated fluorescent material with receiving elements.

Description

Lateral flow device and method for analyzing sample

The present invention relates to a lateral flow analysis device for analyzing and diagnosing a biological sample.

In order to analyze and diagnose substances such as genes or specific proteins contained in biological samples, lateral flow analysis devices such as biochips or lab-on-a-chips are widely used. Such lateral flow analysis devices are disclosed in a number of documents, including US Pat. No. 6,143,576.

The lateral flow analysis device includes a micro flow channel for accommodating a sample and a detector for capturing or detecting a biological sample. In addition, the lateral flow analysis apparatus may include a process of tagging a specific analyte with fluorescence, radiation, a specific protein, or the like, in order to detect the specific analyte.

The lateral flow assay device may utilize an immunoassay to detect a particular analyte contained in a sample. A lateral flow assay device utilizing an immunoassay is used to tag an analyte with fluorescence, radiation, or a specific protein, to capture and capture the analyte using an antibody that is fixed in place and specifically bound to the analyte. By detecting fluorescence, radiation or a specific protein emitted from the tag of the analyzed analyte, it is possible to measure the presence or absence of the analyte and the concentration of the analyte.

In particular, when fluorescence is used to tag an analyte, a laser of a specific wavelength may be irradiated to a lateral flow analyzer to excite a fluorescent tag. In this case, however, a large portion of the laser irradiated to the lateral flow analyzer may be wasted by not reflecting the fluorescent material and reflecting or transmitting the lateral flow analyzer.

Some embodiments of the present invention aim to provide a lateral flow analysis device that can effectively improve the detection sensitivity of an analyte tagged with a fluorescent material.

The lateral flow analysis device according to an embodiment of the present invention for the above purpose, a sample input unit into which a sample is introduced, and a channel connected to the sample input unit, the flow path forming a flow space of the sample ), A photonic crtstal formed on at least a portion of an inner surface of the flow path, and a photonic crtstal fixed to at least a portion of an inner surface of the flow path where the photonic crystal is formed, and specifically binding to a predetermined analyte material. It has a plurality of receptors.

In addition, the photonic crystal may have a pattern formed to be periodically repeated.

In addition, the lateral flow analysis device according to an embodiment of the present invention, the reaction unit (reaction) disposed between the flow path and the sample input unit and a reagent (reagent) containing a fluorescent material bonded to the predetermined material is disposed (reaction) chamber) may be further included.

In addition, the photonic crystal may be formed to be periodically repeated in a first direction and a second direction crossing the first direction.

In addition, the photonic crystal may be formed on the inner lower surface of the flow path, or may be disposed to face each other on the inner surface of the flow path with the flow path therebetween.

The flow path may have an inner bottom surface and an inner top surface, and the photonic crystal may be disposed on the inner bottom surface of the flow path and the inner top surface of the flow path.

The flow path may have a length between the inner bottom surface, the inner top surface and both side surfaces, and the inner bottom surface and the inner top surface and both side surfaces so that a sample located between the inner bottom surface and the inner top surface does not contact the both side surfaces. It may have a groove formed to extend in the direction.

In addition, the lateral flow analysis device is disposed between the flow path and the sample input unit, the first fluorescent material specifically coupled to the first predetermined material, and the second specifically coupled to the second predetermined material Further comprising a reaction unit in which a reagent containing a fluorescent material is disposed, wherein the receptor is arranged to be mixed with the first receptor and the first receptor specifically bound to the first material and specific for the second material It may include a second receptor coupled to.

The photonic crystal may further include a base material formed in a pattern formed periodically and repeatedly, and a TiO 2 layer disposed on the base material and formed in a pattern corresponding to the pattern of the base material.

The photonic crystal may further include an SiO 2 layer disposed between the base material and the TiO 2 layer and formed in a pattern corresponding to the pattern of the base material.

In addition, the method for detecting analyte according to another embodiment of the present invention, the step of the sample is introduced into the sample input unit, the step of combining the analyte and the fluorescent material contained in the sample, and the combined fluorescent material And combining the plurality of receptors fixed to at least a portion of the inner side surface of the flow path in which the photonic crystal is formed.

In addition, in the method for detecting analyte, the photonic crystal may be a two-dimensional photonic crystal that is formed to be periodically repeated in a first direction and a second direction crossing the first direction.

In the method for detecting analyte, the photonic crystal may be disposed to face each other on an inner surface of the flow path with the flow path interposed therebetween.

In the method for detecting a substance to be analyzed, the flow path includes an inner lower surface, an inner upper surface and both side surfaces, and a sample positioned between the inner lower surface and the inner upper surface so as not to contact the both side surfaces. It may have a groove formed to extend in the longitudinal direction of the flow path between the two side surfaces.

According to the lateral flow analysis device according to some embodiments of the present invention, it is possible to greatly improve the detection sensitivity of the analyte tagged with the fluorescent material. Therefore, it is possible to more accurately detect whether the sample contains the analyte, and accuracy can be greatly improved even when measuring the concentration of the analyte.

1 is a schematic side cross-sectional view of a lateral flow analysis apparatus according to an embodiment of the present invention.
FIG. 2 is a schematic plan view of some components of the lateral flow analysis device of FIG. 1.
3A is a schematic side cross-sectional view of the microstructure of the III-A portion of FIG. 2, and FIG. 3B is a schematic side cross-sectional view of the microstructure of the III-B portion of FIG.
4 is a schematic cross-sectional view taken along the line IV-IV for the lateral flow analyzer of FIG. 1.
5 is a view schematically illustrating a process of fluorescence tagging in the lateral flow analysis apparatus of FIG. 1.
FIG. 6A is a diagram schematically illustrating a reaction occurring in the III-A part of FIG. 2, and FIG. 6B is a diagram schematically illustrating a reaction occurring in the III-B part of FIG. 2.
FIG. 7 is a view schematically illustrating a process of detecting fluorescence by irradiating a laser to the lateral flow analyzer of FIG. 1.
8 is a schematic side cross-sectional view of a lateral flow analysis device according to another embodiment of the present invention.
FIG. 9 is a diagram schematically illustrating a process of detecting fluorescence by irradiating a laser to the lateral flow analyzer of FIG. 8.
10 is a schematic side cross-sectional view of a lateral flow analysis device according to another embodiment of the present invention.
FIG. 11 is a schematic side cross-sectional view of the microstructure of part XI of FIG. 10.
12 is a schematic side cross-sectional view of a lateral flow analysis device according to another embodiment of the present invention.
FIG. 13 is a view schematically illustrating a process of detecting fluorescence by irradiating a laser to the lateral flow analyzer of FIG. 12 of the present invention.
14 is a side cross-sectional view schematically showing the microstructure of the detection unit of the lateral flow analysis apparatus according to another embodiment of the present invention.

Hereinafter, a side flow analysis apparatus according to some embodiments of the present invention will be described with reference to the drawings. In the drawings, the relative sizes of the components may be exaggeratedly different from the actual ones for the convenience of description.

1 is a schematic side cross-sectional view of a lateral flow analysis device according to an embodiment of the present invention, Figure 2 is a schematic plan view of a part of the configuration of the lateral flow analysis device of FIG.

1 and 2, the lateral flow analysis device 1 of the present embodiment includes a lower plate 100 and a cover plate 200.

The lower plate 100 has a plate shape as a whole and may be made of glass or synthetic resin. The lower plate 100 is preferably made of an opaque material, but is not necessarily limited thereto.

The cover plate 200 is disposed above the lower plate 100 and partitions a space capable of accommodating a sample therein together with the lower plate 100. The cover plate 200 may be made of glass or synthetic resin of a transparent material to allow light to pass therethrough.

Specifically, the lateral flow analysis apparatus 1 of the present embodiment including the lower plate 100 and the cover plate 200 includes a sample input unit 210, a reaction unit 400, a micro flow path 320, a photonic crystal, An analyte detection unit 152, a first diagnosis validity confirming unit, a second diagnosis validity confirming unit, and a use sample accommodating unit are provided.

The sample inlet 210 serves as an inlet for inserting a sample into the internal space of the lateral flow analysis device 1, and is formed in the cover plate 200 to form an internal space and an external space of the lateral flow analysis device 1. To communicate.

The reaction unit 400 is for reacting the sample introduced into the sample input unit 210 with the reagent and is disposed in the lower space 310 of the sample input unit 210. That is, the sample introduced into the sample input unit 210 comes into contact with the reaction unit 400. The reaction unit 400 includes a reagent for reacting with the sample.

FIG. 5 schematically illustrates a mixture of a reagent and a sample in the reaction unit 400. Referring to FIG. 5, the reagent may include a fluorescent material 410 coupled to an analyte included in the sample, and a sample and a reagent. It may include an indication material 420 to indicate that the mixing is smooth. The fluorescent substance functions as a tag of the analyte (A), and includes a binding portion 412 and a fluorescent labeling portion 414 that specifically bind to the analyte (A) by an antigen-antibody reaction.

The indicator 420 may be moved with the sample to indicate that the sample and the reagent are normally mixed by displaying a specific reaction such as a discoloration reaction in the first diagnosis validity confirming unit 154.

The reaction unit 400 may include an absorbent pad for absorbing a sample, and the reagent included in the reaction unit 400 may be included in the pad in solid or liquid form.

The micro flow path 320 is formed by an inner space defined by the lower plate 100 and the cover plate 200, and is connected to the sample input unit 210 with the reaction unit 400 interposed therebetween. Therefore, the sample introduced into the sample input unit 210 is introduced into the fine flow path 320 through the reaction unit 400. A plurality of protrusions 101 are formed at the connection portion between the micro flow path 320 and the reaction part 400 to prevent the sample from flowing into the micro flow path 320 rapidly or unevenly.

FIG. 4 is a schematic cross-sectional view taken along the line IV-IV of the lateral flow analysis device 1 of FIG. 1, and schematically illustrates a cross section of the fine flow path 320. Referring to FIG. 4, the microchannel 320 has an inner lower surface 322, an inner upper surface 324, and both side surfaces 326 and 328, but has an inner lower surface 322 and both side surfaces 326 and 328, and an inner upper surface 324. ) And both side surfaces 326 and 328, the grooves 325 are formed to extend in the longitudinal direction of the fine flow path 320. By the groove 325, the inner upper surface 324 and the inner lower surface 322 of the microchannel 320 are spaced apart from both side surfaces 326 and 328 of the microchannel 320. As described above, since the inner upper surface 324 and the lower surface 322 of the micro-channel 320 are spaced apart from both side surfaces 326 and 328, the sample S is disposed between the inner upper surface 322 and the lower surface of the micro-channel 320. When flowing through, the sample S is in contact only with the inner upper and lower surfaces 322 and 324 of the micro-channel 320, and does not contact both sides 326 and 328 of the micro-channel 320.

When the sample is in contact with both sides of the micro-channel 320, the moving speed of the sample in contact with both sides of the micro-channel 320 is faster or slower than other parts. That is, a problem may arise that the moving speed of the sample is not uniform throughout. In the case where the deviation of the moving speed of the sample according to the position becomes too large, the sample may be unevenly distributed in the lateral flow analyzer, making it difficult to stepwise react. On the other hand, the moving speed of the sample in contact with both sides of the micro-channel 320, such as the type of the sample, whether both sides of the micro-channel 320 are hydrophilic or hydrophobic, surface roughness of both sides of the micro-channel 320 It is changed by the condition and is not easy to control.

However, in the lateral flow analysis device 1 of the present embodiment, since the sample does not contact both sides 326 and 328 of the micro flow path 320, the sample S in the micro flow path 320 varies in the moving speed according to the position. Has the advantage of being very small. In addition, since the hydrophilic or hydrophobic treatment or the roughening treatment are not required for both sides of the microchannel 320, the manufacturing process is simple.

As shown in FIG. 1, the photonic crystal 102 is formed on the inner lower surface 322 of the microchannel 320 and has a microgrid pattern that is periodically repeated. The photonic crystal 102 may be formed entirely in the fine flow path 320, or may be partially formed in the fine flow path 320, for example, only in the analyte detection unit 152.

The photonic crystal 102 includes a base layer 110 on which a pattern is formed, an intermediate layer 120, and a top layer 130 stacked on the base layer and having the same pattern as the base layer 110.

In the present embodiment, the lower plate 100 forms the base layer 110. Therefore, the fine lattice pattern of the base layer 110 is formed by forming the fine lattice pattern formed on the lower plate 100 surface. As a method for forming a fine lattice pattern on the surface of the lower plate 100, there is a so-called stamp injection method for forming a pattern by injecting a synthetic resin into a mold having a fine lattice pattern.

Specifically, the stamp injection method forms a mold by patterning a fine lattice pattern on a silicon wafer, applies a liquid UV curable polymer to the silicon wafer, and then irradiates the UV curable resin with UV rays to cure it, and then separates the mold from the mold. It includes the process of making. Since the UV cured resin produced through this process is used as the lower plate 100, the lower plate 100 has a fine lattice pattern corresponding to the fine lattice of the silicon wafer.

The intermediate layer 120 may be formed of SiO 2 and is deposited on the base layer 110 by a method such as sputtering or vapor deposition. Since the intermediate layer 120 is deposited in the form of a thin film on the base layer 110, a pattern corresponding to the fine lattice pattern of the base layer 110 is formed on the surface thereof. The intermediate layer 120 may be deposited on the entire surface of the lower plate 100 or may be deposited only on a portion where the fine lattice pattern is formed.

The top layer 130 may be formed of TiO 2, and is deposited on the intermediate layer 120 by a method such as sputtering or vapor deposition. Since the uppermost layer (! 30) is deposited in the form of a thin film on the intermediate layer 120, a pattern corresponding to the fine lattice pattern of the surface of the intermediate layer 120 is formed on the surface of the uppermost layer 130. The uppermost layer 130 may be deposited on the entire surface of the lower plate 100 or may be deposited only on a portion where the fine lattice pattern is formed.

On the other hand, the size of the photonic crystal 102 may be appropriately selected depending on the wavelength of the laser for exciting the fluorescent material and the angle at which the laser is irradiated. For example, in the case of using Cyanine-5 (Cy-5) as the fluorescent material 410, a laser having a wavelength of 632.8 nm is used as the excitation light source, which has a resonance in the photonic crystal 102 with respect to the wavelength of the laser. In order for this to occur, the protrusion amount d of the protrusion 112 of the base layer 110 of the photonic crystal is 20 to 30 nm, and the width W1 of the protrusion 112 is approximately 120 to 130 nm and between the protrusion 112. The spacing (W2) of about 230 to 240 nm, the thickness of the intermediate layer (t2) of about 70 to 90 nm, the thickness of the top layer (t1) of about 110 to 130 nm, the irradiation angle of the laser is about 8 to 10 degrees Can be set to a degree. Since the intermediate layer 120 and the uppermost layer 130 have the same pattern as the base layer 110, the protrusions 122 and 132 are formed in the intermediate layer 120 and the uppermost layer 130, respectively.

The protrusions 112, 122, and 132 of the photonic crystal 102 may extend in the longitudinal direction of the fine flow path 320 or may extend in a direction crossing the longitudinal direction of the fine flow path 320.

The analyte detection unit 152 is used to detect the analyte 11 and is disposed on the inner lower surface 322 of the fine flow path 320 in which the photonic crystal 102 is formed. The analyte detection unit 152 may be markedly distinguished from other parts so as to recognize the location from the outside.

3A is a side cross-sectional view schematically illustrating a microstructure of the analyte detection unit 152. Referring to FIG. 3A, the analyte detection unit 152 may include a plurality of receptors 510 fixed on the photonic crystal 102. Equipped. The receptor 510 serves to capture the analyte by specifically binding to the analyte by an antigen-antibody reaction. That is, the analyte included in the sample is fixedly positioned in the analyte detection unit 152 by the receptor.

The first diagnosis validity confirming unit 154 detects the indicator substance 420 included in the reagent, and serves to confirm that the mixing of the sample and the reagent is performed smoothly, and the lower surface 322 of the fine flow path 320. Is placed on.

3B is a side cross-sectional view schematically illustrating the microstructure of the first diagnosis validity confirming unit 154. Referring to FIG. 3B, the first diagnosis validity confirming unit 154 may be configured to react with an indicator substance included in a reagent. The material fixture 520 may be provided. The indicator substance fixture 520 may be a substance that is discolored by reacting with the indicator substance included in the reagent. Alternatively, when the indicator substance 420 is a material having a color, the indicator substance fixing member 520 collects the indicator substance 420 so that the concentration of the color appears thicker in the first diagnosis validator 154. It may be a material to be fixed.

The second diagnosis validity confirming unit 156 is for checking whether the sample is contaminated and is disposed on the lower surface 322 of the fine flow path 320. The second diagnosis validity confirming unit 156 includes a material causing a specific reaction such as discoloration when contacted with the pollutant so as to detect a pollutant that cannot be included in a normal sample. Accordingly, by observing the change of the second diagnosis validity confirming unit 156, it is possible to determine whether the sample is contaminated.

The use sample accommodating part 330 is for accommodating the sample which passed the micro flow path 320, and is connected to the end side of the micro flow path 320. As shown in FIG. Between the micro-channel 320 and the sample receiving portion 330, the sample of the micro-channel 320 is suddenly introduced into the use sample receiving portion 330 or suppressed unevenly introduced, the use of the sample receiving portion 330 Protruding jaw 103 may be formed to suppress backflow into the micro-channel 320.

Next, the operation and effect of the lateral flow analysis device 1 of the present embodiment will be described.

When the sample is introduced into the sample input unit 210 of the lateral flow analysis device 1 of the present embodiment, the sample reacts with the reagent of the reaction unit 400. When the sample includes the analyte 11, the analyte 11 is fluorescently tagged in combination with the fluorescent material 410 included in the reagent. Meanwhile, since the reagent also includes the indicator 420, the mixture of the sample and the reagent includes the fluorescently tagged analyte 11 and the indicator 420. The sample mixed with the reagent and subjected to the biochemical reaction is introduced into the micro channel 320. The sample introduced into the micro-channel 320 contacts only the inner upper surface 324 and the inner lower surface 322 of the micro-channel 320, and does not contact both sides 326 and 328 of the micro-channel 320. Therefore, the sample in the microchannel 320 has a uniform velocity distribution in the width direction of the microchannel 320, and stably moves in the longitudinal direction of the microchannel 320.

The sample in the micro-channel 320 moves to reach the analyte detection unit 152 including the receptor 510. When the sample reaches the analyte detection unit 152, the fluorescently tagged analyte 11 included in the sample is specifically bound to and fixed to the receptor 510.

When it is determined that the sample has sufficiently reacted with the analyte detection unit 152, the fluorescent substance 410 of the analyte detection unit 152 is irradiated with excitation light to detect the analyte 11. FIG. 7 schematically illustrates a process of detecting the analyte. Referring to FIG. 7, when the laser L of the wavelength λ 1 that excites the fluorescent material 410 is irradiated to the analyte detection unit 152, the analysis is performed. Fluorescence of a specific wavelength λ 2 is emitted from the object detection unit 152. This is because the fluorescent material 410 coupled to the analyte is excited by a laser to emit fluorescence, and by detecting the same by the fluorescent detector R, it may be determined whether the analyte 11 is included in the sample. .

Since the analyte detection unit 152 of the present embodiment is located on the surface of the microchannel 320 in which the photonic crystal 102 is formed, the light intensity is amplified on the surface of the analyte detection unit 152 by the resonant evanescent field effect. do. When the light intensity is amplified on the surface of the analyte detection unit 152 as described above, even if the same laser light source is used, more fluorescent materials are excited and the intensity of the fluorescence emitted from the analyte detection unit 152 may be greatly increased.

In addition, since the surface of the analyte detection unit 152 has a large surface area by the photonic crystal 102, the receptor 510 may be more densely fixed. Accordingly, the analyte 11 tagged with the fluorescent material 410 may be more densely fixed to emit higher intensity fluorescence with respect to the excitation light of the same intensity.

In addition, the photonic crystal 102 of the analyte detection unit 152 may have a property of preventing light of a specific wavelength λ1 from being transmitted. The photonic crystal 102 may transmit the excitation light of a specific wavelength λ1. When the dimension is set to prevent, it is possible to effectively suppress the transmission of the excitation light through the photonic crystal 102 and wasted. That is, the efficiency with which the fluorescent material is excited with respect to the same excitation light can be increased.

Since the intensity of fluorescence obtained through this process can be amplified remarkably as much as several tens of times as compared with the conventional lateral flow analysis device 1, the lateral flow analysis device 1 of the present embodiment can be used to detect an analyte. Sensitivity can be raised significantly.

In addition, when the photonic crystal is entirely formed on the bottom surface of the microchannel 320, a predetermined surface roughness is formed on the surface of the microchannel 320 by the photonic crystal. When the surface roughness of the surface of the micro-channel 320 is formed, the moving speed of the sample passing through the micro-channel 320 may be reduced. If the moving speed of the sample is too fast, the sample may pass without sufficient reaction with the receptor of the analyte detection unit 152. If the surface roughness is formed in the micro-channel 320 by photonic crystal, this problem may be reduced. There is an advantage.

Meanwhile, the intermediate layer 120 of the SiO 2 material of the present embodiment may serve to reduce self-fluorescence emitted from the lower plate 100 to the outside of the lateral flow analysis device 1.

Next, a side flow analysis apparatus according to another embodiment of the present invention will be described with reference to the drawings.

8 is a schematic plan view of the lower plate of the lateral flow analysis device according to another embodiment of the present invention. Referring to FIG. 8, in the lateral flow analysis device 2 of the present embodiment, the protrusions 132 ′ of the photonic crystal 102 ′ are arranged in two dimensions, and a plurality of receptors 510 are fixed to the surface thereof. . Since other configurations are substantially the same as the lateral flow analysis apparatus of FIG. 1, redundant description thereof will be omitted.

Since the lateral flow analysis device 2 of this embodiment includes the photonic crystals 102 'arranged in two dimensions, the effects of optical amplification and specific frequency blocking by the photonic crystals 102' occur in two directions. FIG. 9 is a diagram schematically illustrating irradiation of the excitation light to the analyte detection unit 152 in two two directions. As shown in FIG. 9, the second object perpendicular to the first direction is irradiated with the excitation light of the specific wavelength λ 1 from the first direction to the analyte detection unit 152. By irradiating the analyte detection unit 152 from the direction, both the excitation light in the first direction and the excitation light in the second direction can have the effects of light amplification and transmission blocking. Thus, the excitation reaction of the fluorescent material 410 may be doubled.

As described above, when the photonic crystals 102 'are arranged in two dimensions, even when the excitation light is irradiated in two directions, the effects of light amplification and transmission blocking by the photonic crystals 102' can be obtained in each irradiation direction. As a result, the space for disposing lasers L1 and L2 for irradiating the excitation light is greatly increased. In addition, when it is determined that the intensity of the excitation light is insufficient when one laser is used, the intensity of the excitation light can be easily adjusted by simply placing another laser in another direction without replacing the existing laser with a high-output laser. You can double.

Next, a side flow analysis apparatus according to another embodiment of the present invention will be described with reference to the drawings.

FIG. 10 is a schematic side cross-sectional view of a lateral flow analyzing apparatus according to another embodiment of the present invention. Referring to FIG. 10, the lateral flow analyzing apparatus 3 according to the present exemplary embodiment may have light crystals on the inner upper surface of the microchannel 320. 202 is formed. The photonic crystal 202 of the upper surface of the micro-channel 320 may be formed only on the upper side of the analyte detection unit 152, and the size of the photonic crystal 320 may be equal to or smaller than that of the analyte detection unit 152.

Like the photonic crystal 102 of the inner bottom surface of the microchannel 320, the photonic crystal 202 may be designed to block transmission of excitation light having a specific wavelength.

FIG. 11 schematically illustrates a movement path of the excitation light introduced into the microchannel 320, and like the lateral flow analyzer 3 of the present embodiment, the microchannel 320 may be disposed between the microchannels 320. When the photonic crystals 102 and 202 are formed on the upper and lower surfaces, when the excitation light enters the fine flow path 320 at a predetermined angle, it is trapped between the upper and lower photonic crystals 102 and 202. That is, since the excitation light is not wasted through the fine passage 320, the excitation efficiency of the fluorescent material 410 is greatly increased.

In this case, the photonic crystal 202 of the upper surface of the micro-channel 320 may be formed to have a smaller size than the analyte detection unit 152 so that the excitation light is easily obliquely entering the micro-channel 320.

On the other hand, the photonic crystal 102 of the upper surface of the micro-channel 320 may be formed on the entire upper surface of the micro-channel 320, in this case, the base layer 210 of the photonic crystal 102 is made of a transparent material, The light may be transmitted in the direction in which the excitation light enters into the micro-channel 320, but may not be transmitted in the direction in which the excitation light exits from the micro-channel 320.

Next, a side flow analysis apparatus according to another embodiment of the present invention will be described.

12 is a schematic side cross-sectional view of a lateral flow analysis device according to another embodiment of the present invention.

Referring to FIG. 12, the reagent of the reaction unit 400 of the lateral flow analyzer 4 according to the present embodiment includes a first fluorescent substance 410 and a second fluorescent substance 430. The first fluorescent material 410 and the second fluorescent material 430 have different wavelengths of excitation light, and different wavelengths of fluorescence emitted. For example, the first fluorescent material 410 may be cyanine-5, and the second fluorescent material 430 may be cyanine-3. The first fluorescent substance 410 is specifically bound to the first analyte, and the second fluorescent substance is specifically bound to a second analyte that is distinct from the first analyte. The first fluorescent material 410 fluorescently tags the first analyte, and the second fluorescent material 430 serves to fluorescently tag the second analyte.

The two-dimensional photonic crystal 105 is formed in the analyte detection unit 152, the first receptor 510 specifically coupled to the first analyte, and the second receptor specifically coupled to the second analyte. 530 is fixed.

The other configuration of the lateral flow analysis device 4 of this embodiment is substantially the same as that of the lateral flow analysis device 1 of FIG.

FIG. 13 schematically illustrates a process of detecting fluorescence by irradiating a laser to the analyte detection unit 152 of the present embodiment. Referring to FIG. 13, the first laser L1 for exciting the first fluorescent material 410 irradiates the excitation light of the first wavelength λ1 in the first direction, and excites the second fluorescent material 430. The second laser beam L3 irradiates the excitation light of the second wavelength lambda 2 in the second direction. The irradiation angles and the irradiation directions of the first laser L1 and the second laser L3 may be appropriately set such that transmission blocking and optical amplification may occur by the light crystal 105.

If the sample contains a first analyte and a second analyte, the first analyte and the second analyte are tagged by the first fluorescent material 410 and the second fluorescent material 430, respectively, and then the analyte. It is fixed to the detector 152. Therefore, when the excitation light of the first wavelength λ 1 and the excitation light of the second wavelength λ 2 are irradiated to the analyte detection unit 152, the analyte detection unit 152 causes the fluorescence of the first fluorescent substance 410 to be reduced. Fluorescence by the second fluorescent material 430 is simultaneously emitted.

By capturing this with the fluorescence sensing device R, it can be seen that the sample contains the first analyte and the second analyte. In addition, by measuring the intensity of the fluorescence with the fluorescence detection device (R) it is possible to simultaneously measure the concentration of the first analysis object and the second analysis object contained in the sample. Thus, according to the lateral flow analysis apparatus 4 of a present Example, what is called multiplexing which can detect the several analysis object contained in a sample at once is possible.

In this embodiment, since the photonic crystal 105 is arranged in two dimensions, the transmission block and excitation of the excitation light occur in two directions. Therefore, the laser arrangement space for obtaining the effect of the transmission blocking of the excitation light and the light amplification can be easily secured.

As described above, the side flow analyzing apparatuses 1, 2, 3, and 4 according to some embodiments of the present invention have been described, but the side flow analyzing apparatus of the present invention is not limited to the above-described embodiment.

For example, in the above-described embodiment, it has been described that the analyte 11 contained in the sample is fixed to the analyte detection unit 152 by an antigen-antibody reaction. It may be to fix the analyte to the analyte detection unit 152 by using the combination. FIG. 14 is a view schematically showing the microstructure of the analyte detection unit 152 of the lateral flow analysis apparatus. Referring to FIG. 14, the receptor 530 of the analyte detection unit 152 may perform complementary binding of nucleic acids. In this case, the specific base sequence contained in the sample is bound to DNA or RNA 12. At this time, the DNA or RNA 12 of the specific base sequence included in the sample is also tagged by the fluorescent material 410. Therefore, the DNA or RNA 12 of the specific base sequence included in the sample can be detected by the method of irradiating excitation light and detecting fluorescence as in the above-described embodiment. At this time, the sample may be the result of such a polymer chain reaction (PCR).

In addition, the lateral flow analysis device (1, 2, 3, 4) of the above-described embodiment has been described as having a reaction unit 400, the lateral flow analysis device according to the present invention does not have a reaction unit 400 It may be. In this case, the process of tagging the analyte 11 with the fluorescent material 410 may be performed in advance before the sample is introduced into the lateral flow analyzers 1, 2, 3, and 4.

In addition, the side flow analysis device (1, 2, 3, 4) of the above-described embodiment has been described as having a sample receiving portion 330, the side flow analysis device according to the present invention is a sample receiving portion 330 It may not be provided. When the use sample accommodating part 330 is not provided, the used sample may be discharged to the outside of the lateral flow analyzer.

In addition, in the above-described embodiment, the photonic crystals 102, 102 ', 202, and 105 have the base layers 110 and 210, the intermediate layers 120 and 220 of the SiO 2 material, and the top layers 130 and 230 of the TiO 2 material, but the photo crystals are the base layers 110 and 210. And, it may be formed of only the top layer 130,230 of the TiO 2 material. In addition, the base layers 110 and 210, the intermediate layers 120 and 220, and the top layers 130 and 230 may be replaced with other materials having similar refractive indices.

In addition, the shape of the photonic crystals 102, 202, 103 '105 is not limited to the above-described form may be formed of a combination of various shapes and materials.

In addition, the micro-channel 320 may have a wider shape than the height, but unlike the micro-channel 320, the micro-channel 320 may have a wider shape than the height. In this case, the photonic crystal may be disposed on one side of the micro-channel 320, or may be disposed to face each other on both sides of the micro-channel 320 with the micro-channel 320 therebetween.

In addition, the lateral flow analysis device of the present invention may be used not only for analyzing a biological sample, but also for analyzing chemical substances other than the biological sample, provided that the analyte included in the sample is capable of fluorescent tagging.

It is needless to say that the present invention can be embodied in various forms.

1,2,3,4 ... lateral flow analyzer
100 ... lower plate
102, 202, 102 ', 105 ... photonic crystal
200 ... cover plate
210 ... sample insert
320 ... fine euro
330 ... used sample container
400 ... reaction part
410 ... fluorescent material
510 ... receptor

Claims (18)

A sample input unit into which a sample is input,
A flow path connected to the sample input part and forming a flow space of the sample;
A photonic crystal formed on at least a portion of an inner surface of the flow path,
And a plurality of receptors fixed to at least a portion of an inner surface of the flow path in which the photonic crystal is formed, and having a plurality of receptors that specifically bind to a predetermined analyte. The method of claim 1,
The lateral flow analysis device having the pattern formed to repeat the photonic crystal periodically. The method of claim 1,
Is disposed between the flow path and the sample inlet,
The side flow analysis device further comprises a reaction unit is disposed a reagent comprising a fluorescent material bound to the predetermined material. The method of claim 1,
The photonic crystal,
A lateral flow analysis device which is a two-dimensional photonic crystal that is formed to be periodically repeated in a first direction and a second direction crossing the first direction. The method of claim 1,
The photonic crystal,
And a side flow analysis device disposed between the flow paths so as to face each other on an inner surface of the flow path. The method of claim 5,
The flow path has an inner lower surface and an inner upper surface,
The photonic crystal,
Lateral flow analysis device disposed on the inner bottom surface of the flow path and the inner top surface of the flow path. The method of claim 1,
The flow path includes:
Inner lower surface, inner upper surface and both sides,
And a groove formed to extend in the longitudinal direction of the flow path between the inner lower surface and the inner upper surface and both side surfaces so that a sample located between the inner lower surface and the inner upper surface does not contact the both side surfaces. The method of claim 7, wherein
The photonic crystal,
Lateral flow analysis device formed on the inner bottom surface of the flow path. 9. The method of claim 8,
The photonic crystal,
And a lateral flow analysis device that is also formed on the inner upper surface of the flow path facing the inner lower surface of the flow path. 10. The method of claim 9,
The photonic crystal,
A lateral flow analysis device which is a two-dimensional photonic crystal that is formed to be periodically repeated in a first direction and a second direction crossing the first direction. The method of claim 1,
A reagent disposed between the flow path and the sample input part and including a first fluorescent material specifically bound to a first predetermined material and a second fluorescent material specifically bound to a second predetermined material Further comprises a reaction chamber in which is disposed,
The receptor,
A first receptor specifically bound to the first substance,
A side flow analysis device disposed to be mixed with the first receptor, comprising a second receptor specifically bound to the second material. 12. The method of claim 11,
The photonic crystal,
A lateral flow analysis device which is a two-dimensional photonic crystal that is formed to be periodically repeated in a first direction and a second direction crossing the first direction. 13. The method according to any one of claims 1 to 12,
The photonic crystal,
A base material formed in a pattern formed periodically and repeatedly;
And a TiO 2 layer disposed on the base material and formed in a pattern corresponding to the pattern of the base material. 13. The method according to any one of claims 1 to 12,
The photonic crystal,
And a SiO 2 layer disposed between the base material and the TiO 2 layer and formed in a pattern corresponding to the pattern of the base material. Injecting the sample into the sample input unit;
Combining the analyte and the fluorescent material included in the sample;
And combining the bound fluorescent substance with a plurality of receptors fixed to at least a portion of an inner surface of a flow path in which a photonic crystal is formed. 16. The method of claim 15,
The photonic crystal,
A method for detecting analyte, which is a two-dimensional photonic crystal formed periodically and repeatedly in a first direction and a second direction crossing the first direction. 16. The method of claim 15,
The photonic crystal,
And a method for detecting an analyte to be disposed so as to face each other on an inner surface of the flow path with the flow path interposed therebetween. 16. The method of claim 15,
The flow path includes:
Inner lower surface, inner upper surface and both sides,
And a groove formed to extend in the longitudinal direction of the flow path between the inner lower surface and the inner upper surface and both side surfaces so that a sample located between the inner lower surface and the inner upper surface does not contact the both side surfaces. .

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