Patent Publication Number: US-2022236262-A1

Title: Biosensor

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This U.S. non-provisional patent application claims priority under 35 U.S.C. § 119 of Korean Patent Application No. 10-2021-0010693, filed on Jan. 26, 2021, the entire contents of which are hereby incorporated by reference. 
     BACKGROUND 
     The present disclosure herein relates to a biosensor, and more particularly, to an optical biosensor including a precise nano-optical structure having a small size. 
     A biosensor is a sensor that is constituted by a biomaterial and a signal detection part to detect a material to be analyzed. The bio-sensing material may be an enzyme, antibodies, DNAs, etc. that are capable of selectively reacting to be bound with a specific material. The signal detection part detects a signal of the biomaterial by using various physicochemical methods such as minute electrical changes (voltage, current, resistance, etc.) depending on the presence or absence of biomaterials, changes in fluorescence intensity due to chemical reactions, and changes in optical spectrum. The biosensor is applied in the medical fields, the environmental fields, and the analysis of infectious pathogens, and the fields of application of the biosensor are very wide in ranging to sensors for military, industry, and research. 
     The optical biosensor uses a method of analyzing the presence or absence of the biomaterial by converting an optical signal emitted from the biomaterial into an electrical signal by using a light emitting device and a photodetector. As the optical method for detecting the biomaterials, mainly, a labeling biosensor, in which an antibody is labeled with a fluorescent material, etc., to detect a corresponding antigen, thereby implementing quantification of the antigen to be analyzed in proportion to the intensity of the fluorescence measured from the biosensor is widely used. 
     SUMMARY 
     The present disclosure provides a biosensor including a precise nano-optical structure having a small size. 
     Technical objects to be solved by the present invention are not limited to the aforementioned technical objects and unmentioned technical objects will be clearly understood by those skilled in the art from the specification and the appended claims. 
     An embodiment of the inventive concept provides a biosensor including: a substrate; an optical structure provided on the substrate; and a cover provided on the substrate and having a bridge shape that is in contact with a top surface of the substrate at both sides of the optical structure, wherein the cover has a channel extending in a first direction, the optical structure is provided inside the channel, and the optical structure is configured to capture biomaterials that travel through the channel. 
     In an embodiment, the optical structure may include a lower layer, an active layer, and an upper layer, which are sequentially stacked on the substrate, wherein the active layer may be interposed between the lower layer and the upper layer. 
     In an embodiment, the optical structure may include a Group III-V semiconductor material, the lower layer and the upper layer may include the same semiconductor material, and the active layer may include a semiconductor material different from that of each of the lower layer and the upper layer. 
     In an embodiment, the optical structure may have a plurality of nanoholes passing through the lower layer, the active layer, and the upper layer, the nanoholes may be arranged in the first direction and spaced apart from each other in the first direction, and a diameter and a period of each of the nanoholes may vary in the first direction. 
     In an embodiment, the diameter of each of the nanoholes may decrease in the first direction from one end of the optical structure toward a central portion of the optical structure and may increase in the first direction from the central portion toward the other end of the optical structure, which faces the one end. 
     In an embodiment, the biosensor may further include a CMOS camera or CCD camera provided on the optical structure. 
     In an embodiment, the optical structure may include a lower layer on the substrate and an upper layer on a partial area of the lower layer, wherein the optical structure may have a plurality of nanoholes passing through the lower layer to expose the top surface of the substrate, the nanoholes may be arranged in the first direction and spaced apart from each other in the first direction, and a diameter and a period of each of the nanoholes may vary in the first direction. 
     In an embodiment, the upper layer may include one of a semiconductor material or transition metal dichalcogenide, graphene, and hexagonal boron nitride (hBN). 
     In an embodiment, the biosensor may further include a plurality of antibodies provided on the optical structure, wherein the antibodies may be arranged along the first direction on a top surface of the optical structure, and the antibodies may be configured to capture the biomaterials that travel through the channel. 
     In an embodiment, the optical structure may include a plurality of meta-material unit elements having a geometric period, wherein the meta-material unit elements may be configured to diffract incident light irradiated from a bottom surface of the substrate toward the optical structure. 
     In an embodiment, the optical structure may be provided in plurality, and the optical structures may be arranged along the first direction and a second direction crossing the first direction. 
     In an embodiment of the inventive concept, a biosensor includes: a substrate; an optical structure having a bar shape extending in a first direction on the substrate; and a cover provided on the substrate and having a bridge shape that is in contact with a top surface of the substrate at both sides of the optical structure, wherein the cover has a channel extending in the first direction, the optical structure is provided inside the channel, and the optical structure includes: a lower layer on the substrate; an upper layer on the lower layer; and an active layer interposed between the lower layer and the upper layer, wherein the optical structure has a plurality of nanoholes passing through the lower layer, the active layer, and the upper layer. 
     In an embodiment, the active layer may have quantum dots configured to control photons of laser light emitted from the optical structure, and the active layer may include a material different from that of each of the lower layer and the upper layer. 
     In an embodiment, a diameter of each of the nanoholes disposed at a central portion of the optical structure may be less than that of each of the nanoholes disposed at both ends of the optical structure. 
     In an embodiment, the optical structure may be provided in plurality, the optical structures may be arranged along the first direction and a second direction crossing the first direction, the optical structures arranged along the first direction may be spaced apart from each other in the first direction, and sidewalls of the optical structures are aligned with each other, and the optical structures arranged along the second direction may be spaced apart from each other in the second direction, and sidewalls of the optical structures may be aligned with each other. 
     In an embodiment of the inventive concept, a biosensor includes: a measuring unit configured to measure an emission pattern or a diffraction pattern; a data storage unit configured to store data including the emission pattern or the diffraction pattern measured in the measuring unit; a data learning unit is configured to perform machine learning through the data transmitted from the data storage unit and determine a presence or absence of the biomaterial and/or the number of biomaterials through the data; and a display unit configured to visualize information determined by the data learning unit, wherein the measuring unit includes: a substrate; an optical structure provided on the substrate; and a cover having a bridge shape that is in contact with a top surface of the substrate at both sides of the optical structure, wherein the cover has a channel extending in a first direction, the optical structure is provided inside the channel, and the optical structure is configured to capture biomaterials that travel through the channel. 
     In an embodiment, the data learning unit may be trained to determine a presence or absence of the biomaterial and/or the number of biomaterials through a change in at least one of a resonance wavelength, a phase, or polarization. 
     In an embodiment, the optical structure may include: a lower layer on the substrate; an upper layer on the lower layer; and an active layer interposed between the lower layer and the upper layer, wherein the optical structure may have a plurality of nanoholes passing through the lower layer, the active layer, and the upper layer. 
     In an embodiment, the optical structure may include a plurality of meta-material unit elements having a geometric period, wherein the meta-material unit elements may be configured to diffract incident light irradiated from a bottom surface of the substrate toward the optical structure. 
     In an embodiment, the optical structure may be provided in plurality, and the optical structures may be arranged along the first direction and a second direction crossing the first direction. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       The accompanying drawings are included to provide a further understanding of the inventive concept, and are incorporated in and constitute a part of this specification. The drawings illustrate exemplary embodiments of the inventive concept and, together with the description, serve to explain principles of the inventive concept. In the drawings: 
         FIG. 1  is an exploded perspective view for explaining a biosensor according to embodiments of the inventive concept; 
         FIG. 2  is a perspective view for explaining an optical structure of the biosensor according to embodiment of the inventive concept; 
         FIGS. 3A and 3B  are plan and cross-sectional views for explaining the optical structure of the biosensor according to embodiments of the inventive concept, wherein  FIG. 3B  is a cross-sectional view taken along line I-I′ of  FIG. 3A ; 
         FIGS. 4A, 5A, 6A, and 7A  are perspective views for explaining an operation of the biosensor according to embodiment of the inventive concept; 
         FIGS. 4B, 5B, 6B, and 7B  are pictures illustrating an emission pattern of the optical structure of the biosensor according to embodiments of the inventive concept; 
         FIG. 8  is an exploded perspective view for explaining a biosensor according to embodiments of the inventive concept; 
         FIGS. 9A to 9H  are plan views for explaining an optical structure of the biosensor according to embodiments of the inventive concept; 
         FIGS. 10A to 17A  are perspective views for explaining an operation of the biosensor according to embodiment of the inventive concept; 
         FIGS. 10B to 17B  are pictures illustrating a diffraction pattern of the optical structure of the biosensor according to embodiments of the inventive concept; and 
         FIG. 18  is a conceptual view for explaining a biosensor and a method for determining presence or absence of a biomaterial using the biosensor according to embodiments of the inventive concept. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments of the inventive concept will be described with reference to the accompanying drawings so as to sufficiently understand constitutions and effects of the inventive concept. 
     The present invention is not limited to the embodiments disclosed below, but should be implemented in various forms, and various modifications and changes may be made. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the present invention to those skilled in the art. Further, the present invention is only defined by scopes of claims. In the accompanying drawings, the components are shown enlarged for the sake of convenience of explanation, and the proportions of the components may be exaggerated or reduced for clarity of illustration. 
     In the following description, the technical terms are used only for explaining a specific exemplary embodiment while not limiting the present invention. Unless terms used in embodiments of the present invention are differently defined, the terms may be construed as meanings that are commonly known to a person skilled in the art. 
     In this specification, the terms of a singular form may include plural forms unless specifically mentioned. The meaning of ‘comprises’ and/or ‘comprising’ specifies a component, a step, an operation and/or an element does not exclude other components, steps, operations and/or elements. 
     When a layer is referred to herein as being ‘on’ another layer, it may be formed directly on the top of the other layer or a third layer may be interposed between them. 
     It will be understood that although the terms first and second are used herein to describe various regions, layers, and the like, these regions and layers should not be limited by these terms. These terms are used only to discriminate one region or layer from another region or layer. Therefore, a portion referred to as a first portion in one embodiment can be referred to as a second portion in another embodiment. An embodiment described and exemplified herein includes a complementary embodiment thereof. Like reference numerals refer to like elements throughout. 
     Hereinafter, embodiments of a biosensor according to the inventive concept will be described in detail with reference to the drawings. 
       FIG. 1  is an exploded perspective view for explaining the biosensor according to embodiments of the inventive concept.  FIG. 2  is a perspective view for explaining an optical structure of the biosensor according to embodiment of the inventive concept. 
     Referring to  FIGS. 1 and 2 , the biosensor according to the inventive concept may include a substrate  10 , an optical structure  30 , and a cover  50 . The substrate  10  may have a flat plate shape extending parallel to a first direction D 1  and a second direction D 2 . A top surface of the substrate  10  may be a plane perpendicular to a third direction D 3 . The first direction D 1  to the third direction D 3  may be, for example, directions orthogonal to each other. The substrate  10  may include a material that is transparent to a wavelength of light incident into the optical structure  30  and a wavelength of light emitted from the optical structure  30 . 
     The optical structure  30  may be provided on the substrate  10 . The optical structure  30  may be, for example, a bar-shaped nano laser extending in the first direction D 1 . In other words, a length of the optical structure  30  in the first direction D 1  may be greater than a length of the optical structure  30  in the second direction D 2 . The length of the optical structure  30  in the first direction D 1  may be, for example, about 3 μm or more. The length of the optical structure  30  in the second direction D 2  may be, for example, about 200 nm to 700 nm. A thickness of the optical structure  30  in the third direction D 3  may be, for example, about 100 nm to 300 nm. However, this is merely exemplary, and the embodiment of the inventive concept is not limited thereto. For example, the optical structure  30  may have various shapes and sizes. 
     The optical structure  30  may include a lower layer  31 , an active layer  32 , and an upper layer  33 , which are sequentially stacked on the substrate  10 . The optical structure  30  may include, for example, Group III-V semiconductor material. The lower layer  31  and the upper layer  33  may include the same semiconductor material. The lower layer  31  and the upper layer  33  may include, for example, InP. 
     The active layer  32  may be interposed between the lower layer  31  and the upper layer  33 . The active layer  32  may include a semiconductor material different from that of each of the lower layer  31  and the upper layer  33 . The active layer  32  may include, for example, InGaAsP. The active layer  32  may have quantum dots, which may control photons of laser light emitted from the optical structure  30 . 
     The optical structure  30  may have a plurality of nanoholes  35  passing through the lower layer  31 , the active layer  32 , and the upper layer  33 . The nanoholes  35  may be arranged along the first direction D 1  and may be spaced apart from each other in the first direction D 1 . A diameter  35   r  of each of the nanoholes  35  may be less than that of the optical structure  30  in the second direction D 2 . The diameter  35   r  of each of the nanoholes  35  may be, for example, about 100 nm to 500 nm. A top surface of each of the nanoholes  35  may have, for example, a circular shape or an elliptical shape, but the embodiment of the inventive concept is not limited thereto. 
     The diameter  35   r  and a period  35   p  of each of the nanoholes  35  may not be constant. The diameter  35   r  and the period  35   p  of each of the nanoholes  35  may vary in the first direction D 1 . For example, the diameter  35   r  and period  35   p  of each of the nanoholes  35  may decrease from one end of the optical structure  30  to a central portion of the optical structure  30  in the first direction D 1 , and may increase from the central portion of the optical structure  30  to the other end of the optical structure  30 , which faces the one end, in the first direction D 1 . 
     The central portion of the optical structure  30  in which the nano-holes  35 , each of which has a relatively small diameter  35   r,  are disposed may correspond a resonator region of the nano-laser. Both ends of the optical structure  30  in which the nano-holes  35 , each of which has a relatively large diameter  35   r,  are disposed may correspond to mirror regions of the nano-laser. Specifically, when light is incident into the optical structure  30 , the central portion of the optical structure  30  may generate resonance, and both the ends of the optical structure  30  may reflect the light so that the light is captured to the central portion of the structure  30  without being scattered. 
     The resonance wavelength at the central portion of the optical structure  30  may vary depending on the arrangement of the nanoholes  35 , and the diameter  35   r  and/or the period  35   p  of each of the nanoholes  35 . In addition, a quality factor of the nano-laser may vary depending on the size of the optical structure  30  and the wavelength of the incident light. 
     However, this is merely exemplary, and the embodiment of the inventive concept is not limited thereto. For example, the arrangement of the nanoholes  35 , and the diameter  35   r  and/or the period  35   p  of each of the nanoholes  35  may be different from those shown. 
     The cover  50  may be provided on the substrate  10  and may have a bridge shape that is in contact with the top surface of the substrate  10  at both the sides of the optical structure  30 . The cover  50  may include a material that is transparent with respect to a wavelength of light incident into the optical structure  30  and a wavelength of light emitted from the optical structure  30 . 
     The cover  50  may have a channel  51  extending in the first direction D 1 . The optical structure  30  may be provided inside the channel  51 . A width of the channel  51  in the first direction D 1  may be greater than the length of the optical structure  30  in the first direction D 1 . A width of the channel  51  in the second direction D 2  may be greater than or equal to the length of the optical structure  30  in the second direction D 2 . That is, the cover  50  may be in contact with both the side surfaces of the optical structure  30  or may be spaced apart from each other in the second direction D 2 . A height of the channel  51  in the third direction D 3  may be greater than the thickness of the optical structure  30  in the third direction D 3 . That is, the cover  50  may be spaced apart from the top surface of the optical structure  30  in the third direction D 3 . 
       FIGS. 3A and 3B  are plan and cross-sectional views for explaining the optical structure of the biosensor according to embodiments of the inventive concept, wherein  FIG. 3B  is a cross-sectional view taken along line I-I′ of  FIG. 3A . 
     Referring to  FIGS. 3A and 3B , the optical structure  30  may include a lower layer  37  on the substrate  10  and an upper layer  39  on a partial area of the lower layer  37 . A top surface of the upper layer  39  may have an elliptical or rectangular shape in which a length in the first direction D 1  is greater than a length in the second direction D 2 , but the embodiment of the inventive concept is not limited thereto. 
     The substrate  10  may include, for example, silicon oxide. The lower layer  37  may include, for example, silicon. The upper layer  39  may include a two-dimensional material. The upper layer  39  may be, for example, one of a semiconductor material (e.g., InGaAsP) or transition metal dichalcogenide (e.g., MoS2, MoSe2, WS2, WSe2, MoTe2, WTe2, etc.), graphene, and hexagonal boron nitride (hBN). 
     The lower layer  37  may have, for example, a photonic crystal structure. The upper layer  39  may have, for example, a bound state in the continuum (BIC) structure. 
     The optical structure  30  may have a plurality of nanoholes  38 . The nanoholes  38  may not be provided under the upper layer  39 . That is, the nanoholes  38  may not overlap the upper layer  39  in the third direction D 3 . The nanoholes  38  may pass through the lower layer  37  to expose the top surface of the substrate  10 . The nanoholes  38  may be arranged along the first direction D 1  and may be spaced apart from each other in the first direction D 1 . A diameter  38   r  of each of the nanoholes  38  may be less than a length of the lower layer  37  in the second direction D 2 . A diameter  38   r  of each of the nanoholes  38  may be, for example, about 100 nm to 500 nm. A top surface of each of the nanoholes  38  may have, for example, a circular shape or an elliptical shape, but the embodiment of the inventive concept is not limited thereto. 
     The diameter  38   r  and a period  38   p  of each of the nanoholes  38  may not be constant. For example, the diameter  35   r  and period  35   p  of each of the nanoholes  35  may decrease from one end of the lower layer  37  to a central portion of the lower layer  37  in the first direction D 1 , and may increase from the central portion of the lower layer  37  to the other end of the lower layer  37 , which faces the one end, in the first direction D 1 . 
     The optical structure  30  of the biosensor according to the inventive concept is not limited to that described with reference to  FIGS. 2, 3A and 3B , and various planar lasers based on a semiconductor material may be used as the optical structure  30 . 
       FIGS. 4A, 5A, 6A, and 7A  are perspective views for explaining an operation of the biosensor according to embodiment of the inventive concept.  FIGS. 4B, 5B, 6B, and 7B  are pictures illustrating an emission pattern of the optical structure of the biosensor according to embodiments of the inventive concept. 
     Referring to  FIGS. 4A and 4B , first incident light IL 1  may be irradiated to the central portion of the optical structure  30 , and first emission light EL 1  may be generated from the central portion of the optical structure  30 . Although it is illustrated that the first incident light IL 1  is obliquely incident on the top surface of the optical structure  30 , the embodiment of the inventive concept is not limited thereto, and the first incident light IL 1  may be incident at an angle different from that illustrated. The first incident light IL 1  may have energy greater than an energy gap of the Group III-V semiconductor material of the optical structure  30 . The first incident light IL 1  may have a wavelength of, for example, a visible ray band. The optical structure  30  may generate the first emission light EL 1  corresponding to the energy gap of the Group III-V semiconductor material through down conversion. The first emission light EL 1  may have a wavelength of, for example, an infrared band. However, the embodiment of the inventive concept is not limited thereto, and when the optical structure  30  includes a material for adjusting the energy gap of the Group III-V semiconductor material, the first emission light EL 1  may have a wavelength in the visible ray band. 
     The first emission light EL 1  may be measured by a CMOS camera or a CCD camera on the optical structure  30 , and the emission pattern of  FIG. 4B  represents the first emission light EL 1 . Hereinafter, for convenience of description, descriptions of the contents that are substantially the same as those described with reference to  FIGS. 4A and 4B  will be omitted, and differences will be described in detail. 
     Referring to  FIGS. 5A and 5B , a fluid including biomaterials BM may travel in the first direction D 1  through the channel  51  of the cover  50 . The biomaterials BM may include, for example, proteins, disease diagnosis-related biomarkers, viruses, bacteria, and the like. At least some of the biomaterials BM may be captured in the nanoholes  35  of the optical structure  30 . 
     Thereafter, second incident light IL 2  may be irradiated to the central portion of the optical structure  30 , and second emission light EL 2  may be generated from the central portion of the optical structure  30 . The second incident light IL 2  may have substantially the same wavelength and intensity as the first incident light IL 1 . 
     Due to the biomaterials BM captured in the nanoholes  35 , the second emission light EL 2  may have a wavelength and intensity different from those of the first emission light EL 1 . Thus, an emission pattern (an emission pattern of the second emission light EL 2 ) of  FIG. 5B  may be different from the emission pattern (the emission pattern of the first emission light EL 1 ) of  FIG. 4B . 
     Referring to  FIGS. 6A and 6B , the biosensor according to the inventive concept may further include a plurality of antibodies AB provided on the optical structure  30 . The antibodies AB may be arranged along the first direction D 1  on the top surface of the optical structure  30  and may be spaced apart from each other in the first direction D 1 . For example, the antibodies AB may be arranged in two rows on the top surface of the optical structure  30 , and the rows may be spaced apart from each other in the second direction D 2 . Each of the antibodies AB may have, for example, a Y-shape. 
     Third incident light IL 3  may be irradiated to the central portion of the optical structure  30  provided with the antibodies AB on the top surface thereof, and third emitted light EL 3  may be generated from the central portion of the optical structure  30 . The third incident light IL 3  may have substantially the same wavelength and intensity as each of the first and second incident lights IL 1  and IL 2 . The third emission light EL 3  may have a wavelength and intensity similar to that of the first emission light EL 1 . An emission pattern (an emission pattern of the third emission light EL 3 ) of  FIG. 6B  may be similar to the emission pattern (the emission pattern of the first emission light EL 1 ) of  FIG. 4B . 
     Referring to  FIGS. 7A and 7B , a fluid including biomaterials BM may travel in the first direction D 1  through the channel  51  of the cover  50 . At least some of the biomaterials BM may be captured on the antibodies AB on the optical structure  30  (or in the nanoholes  35  of the optical structure  30 ). 
     Thereafter, fourth incident light IL 4  may be irradiated to the central portion of the optical structure  30 , and fourth emission light EL 4  may be generated from the central portion of the optical structure  30 . The fourth incident light IL 4  may have substantially the same wavelength and intensity as each of the first to third incident light IL 1 , IL 2 , and IL 3 . 
     Due to the biomaterials BM captured on the antibodies AB (or in the nanoholes  35 ), the fourth emission light EL 4  may have a wavelength and intensity different from those of the third emission light EL 3 . Thus, an emission pattern (the emission pattern of the fourth emission light EL 4 ) of  FIG. 7B  may be different from the emission pattern (the emission pattern of the third emission light EL 3 ) of  FIG. 6B . 
       FIG. 8  is an exploded perspective view for explaining a biosensor according to embodiments of the inventive concept. Hereinafter, for convenience of description, descriptions of the contents that are substantially the same as those described with reference to  FIGS. 1 and 2  will be omitted, and differences will be described in detail. 
     Referring to  FIG. 8 , a biosensor according to the inventive concept may include a substrate  10 , an optical structure  30 , and a cover  50 . The optical structure  30  may include a plurality of meta-material groups MG, and each meta-material group MG may include a plurality of meta-material unit elements MU having a geometric period. The plurality of meta-material unit elements MU may be arranged with a specific period in each meta-material group MG. As used herein, the term ‘meta-material’ refers to a structure having a geometric period designed using existing materials rather than a specific material, and a plane on which the meta-material is provided may be referred to as a ‘meta-surface’. 
     A top surface of each of the meta-material unit elements MU may have, for example, a circular shape or an elliptical shape, but the embodiment of the inventive concept is not limited thereto. For example, the top surface of each of the meta-material unit elements MU may have various shapes as described with reference to  FIGS. 9A to 9H . 
       FIGS. 9A to 9H  are plan views for explaining an optical structure of the biosensor according to embodiments of the inventive concept. Specifically,  FIGS. 9A to 9H  illustrate top surfaces of the meta-material group MG or the meta-material unit element MU of the optical structure described with reference to  FIG. 8 . 
     Referring to  FIG. 9A , the meta-material group MG may include two meta-material unit elements MU. A top surface of each of the meta-material unit elements MU may have, for example, an elliptical shape. The meta-material unit elements MU of the meta-material group MG may be disposed bilaterally symmetrically. 
     Referring to  FIGS. 9B and 9C , the meta-material group MG may include one meta-material unit element MU. Referring to  FIG. 9B , the top surface of the meta-material unit element MU may have, for example, a donut shape with a hole therein. The hole may be disposed at a center of the meta-material unit element MU or may be disposed close to an edge. The hole may have a circular shape, an elliptical shape or a polygonal shape. 
     Referring to  FIG. 9C , the top surface of the meta-material unit element MU may have a polygonal shape. The top surface of the meta-material unit element MU may have, for example, a concave polygonal shape in which at least one interior angle is in a range of 180 degrees and 360 degrees, but the embodiment of the inventive concept is not limited thereto. For example, the top surface of the meta-material unit element MU may have a convex polygonal shape. 
     Referring to  FIGS. 9D and 9E , the meta-material group MG may include two meta-material unit elements MU. Referring to  FIG. 9D , a top surface of each of the meta-material unit elements MU may have, for example, an arc shape. The meta-material unit elements MU may have different sizes and/or lengths. 
     Referring to  FIG. 9E , the top surface of each of the meta-material unit elements MU may have, for example, a rectangular shape, and the meta-material unit elements MU may extend in parallel with each other. The meta-material unit elements MU may have different sizes and/or lengths. 
     Referring to  FIGS. 9G and 9H , the meta-material group MG may include three or more meta-material unit elements MU. Referring to  FIG. 9G , a top surface of each of the meta-material unit elements MU may have a circular shape or an elliptical shape, and the meta-material unit elements MU may have the same size. The meta-material unit elements MU may be arranged with a constant period and may be aligned in two directions crossing each other. 
     Referring to  FIG. 9H , a top surface of each of the meta-material unit elements MU may have a circular shape or an elliptical shape. One of the meta-material unit elements MU may be disposed at the center of the meta-material group MG, and the others may surround the meta-material unit element disposed at the center. The size of one of the meta-material unit elements MU disposed at the center may be different from the size of each of the others. 
     The meta-material group MG and the meta-material unit elements MU of  FIGS. 9A to 9H  are merely exemplary, and thus, the embodiment of the inventive concept is not limited thereto. For example, each of the meta-material group MG or the meta-material unit elements MU may have a structure having a geometric period and also may have a geometric period that is repeated itself. In addition, each of the meta-material group MG and the meta-material unit elements MU of  FIGS. 9A to 9H  may have quantum dots that emit light. 
       FIGS. 10A to 13A  are perspective views for explaining an operation of the biosensor according to embodiment of the inventive concept.  FIGS. 10B to 13B  are pictures illustrating a diffraction pattern of the optical structure of the biosensor according to embodiments of the inventive concept 
     Referring to  FIGS. 10A and 10B , fifth incident light IL 5  may be irradiated to the optical structure  30 . The fifth incident light IL 5  may be irradiated in the third direction D 3  from a bottom surface of the substrate  10  toward the optical structure  30 . The fifth incident light IL 5  may be irradiated toward any one of the meta-material groups MG. 
     The fifth incident light IL 5  may be diffracted by the meta-material unit elements MU of the meta-material groups MG and may be emitted as fifth emission light EL 5 . The fifth emission light EL 5  may be emitted in the third direction D 3  from the top surface of the substrate  10  toward the cover  50 . The fifth emission light EL 5  may be emitted from one of the meta-material groups MG. 
     The fifth emitted light EL 5  may be measured by a CMOS camera or a CCD camera on the optical structure  30 , and a diffraction pattern of  FIG. 10B  represents the fifth emission light EL 5 . Hereinafter, for convenience of description, descriptions of the contents that are substantially the same as those described with reference to  FIGS. 10A and 10B  will be omitted, and differences will be described in detail. 
     Referring to  FIGS. 11A and 11B , a fluid including biomaterials BM may travel in the first direction D 1  through the channel  51  of the cover  50 . The biomaterials BM may include, for example, proteins, disease diagnosis-related biomarkers, viruses, bacteria, and the like. At least some of the biomaterials BM may be captured on the meta-material unit elements MU of the optical structure  30 . 
     Thereafter, sixth incident light IL 6  may be irradiated to the optical structure  30 , and sixth emission light EL 6  may be emitted from the optical structure  30 . The sixth incident light IL 6  may have substantially the same wavelength and intensity as the fifth incident light IL 5 . 
     Due to the biomaterials BM captured on the meta-material unit elements MU, the diffraction pattern (the diffraction pattern of the sixth emission light EL 6 ) of  FIG. 11B  may be different from the diffraction pattern (the fifth emission light EL 5 ) of  FIG. 10B . 
     Referring to  FIGS. 12A and 12B , the biosensor according to the inventive concept may further include a plurality of antibodies AB provided on the optical structure  30 . Specifically, the antibodies AB may be provided on the top surface of each of the meta-material unit elements MU. The antibodies AB may be arranged along the first direction D 1  on the top surface of the optical structure  30  and may be spaced apart from each other in the first direction D 1 . For example, the antibodies AB may be arranged in two rows on the top surface of the optical structure  30 , and the rows may be spaced apart from each other in the second direction D 2 . Each of the antibodies AB may have, for example, a Y-shape. 
     Seventh incident light IL 7  may be irradiated to the optical structure  30  provided with the antibodies AB on a top surface thereof, and seventh emission light EL 7  may be emitted from the optical structure  30 . The seventh incident light IL 7  may have substantially the same wavelength and intensity as each of the fifth and sixth incident lights IL 5  and IL 6 . A diffraction pattern (a diffraction pattern of the seventh emission light EL 7 ) of  FIG. 12B  may be similar to the diffraction pattern (the diffraction pattern of the fifth emission light EL 5 ) of  FIG. 10B . 
     Referring to  FIGS. 13A and 13B , a fluid including the biomaterials BM may travel in the first direction D 1  through the channel  51  of the cover  50 . At least some of the biomaterials BM may be captured on the antibodies AB on the optical structure  30  (or the meta-material unit elements MU of the optical structure  30 ). 
     Thereafter, eighth incident light IL 8  may be irradiated to the optical structure  30 , and an eighth emission light EL 8  may be emitted from the optical structure  30 . The eighth incident light IL 8  may have substantially the same wavelength and intensity as each of the fifth to seventh incident light IL 5 , IL 6 , and IL 7 . 
     Due to the biomaterials BM captured on the antibodies AB (or the meta-material unit elements MU), the diffraction pattern (the diffraction pattern of the eighth emission light EL 8 ) of  FIG. 13B  may be different from the diffraction pattern (the diffraction pattern of the seventh emission light EL 7 ) of  FIG. 12B . 
       FIGS. 14A to 17A  are perspective views for explaining an operation of the biosensor according to embodiment of the inventive concept.  FIGS. 14B to 15B  are pictures illustrating an emission pattern of the optical structure of the biosensor according to embodiments of the inventive concept, and  FIGS. 16B to 17B  are pictures illustrating a diffraction pattern of the optical structure of the biosensor according to embodiments of the inventive concept. Specifically,  FIGS. 14A to 17A  illustrate a plurality of optical structures  30  or a plurality of meta-material groups MG arranged in an array form, through which a large-capacity sample may be inspected. 
     Referring to  FIGS. 14A and 14B , the biosensor according to the inventive concept may include a substrate  10  and a plurality of optical structures  30  arranged on the substrate  10 . Each of the optical structures  30  may be substantially the same as the optical structure  30  described with reference to  FIGS. 1 and 2 . The optical structures  30  may be arranged along the first direction D 1  and the second direction D 2 . The optical structures  30  arranged along the first direction D 1  may be spaced apart from each other in the first direction D 1 , and sidewalls of the optical structures  30  may be aligned with each other. The optical structures  30  arranged along the second direction D 2  may be spaced apart from each other in the second direction D 2 , and sidewalls of the optical structures  30  may be aligned with each other. However, this is merely exemplary, and the embodiment of the inventive concept is not limited thereto. For example, an arrangement method of the plurality of optical structures  30  may be different from those shown above. 
     The biosensor according to the inventive concept may further include a dielectric layer  20  that covers a top surface of the substrate  10  and exposes a top surface of each of the optical structures  30 . The dielectric layer  20  may cover a sidewall of each of the optical structures  30 . A top surface of the dielectric layer  20  may be, for example, substantially coplanar with the top surface of each of the optical structures  30 . 
     When a fluid flows through each of the optical structures  30 , the biomaterials BM may be captured on at least some of the optical structures  30 . Due to the biomaterials BM captured in the nanoholes  35  of the optical structures  30 , the optical structures  30  on which the biomaterials BM are captured may have an emission pattern different from that of each of the optical structures  30  having no biomaterials BM. The emission pattern of  FIG. 14B  represents emission patterns generated from the plurality of optical structures  30 . 
     Referring to  FIGS. 15A and 15B , a plurality of antibodies AB may be provided on at least some of the optical structures  30  in addition to those described with reference to  FIGS. 14A and 14B . The arrangement method of the antibodies AB may be substantially the same as described with reference to  FIG. 6A . 
     When a fluid flows through each of the optical structures  30 , the biomaterials BM may be captured on the antibodies AB on at least some of the optical structures  30  (or in the nanoholes  35  of at least some of the optical structures  30 ). Due to the biomaterials BM captured on the antibodies AB (or in the nanoholes  35 ), each of the optical structures  30  on which the biomaterials BM are captured may have an emission pattern different from that of each of the optical structures  30  having no biomaterials BM. The emission pattern of  FIG. 15B  represents emission patterns generated from the plurality of optical structures  30 . 
     Referring to  FIGS. 16A and 16B , the biosensor according to the inventive concept may include a substrate  10  and an optical structure  30  on the substrate  10 . The optical structure  30  may include a plurality of meta-material groups MG. Each of the meta-material groups MG may include a plurality of meta-material unit elements MU. The meta-material groups MG may be arranged in the first direction D 1  and the second direction D 2 . The meta-material groups MG arranged along the first direction D 1  may be spaced apart from each other in the first direction D 1 , and the meta-material groups MG arranged along the second direction D 2  may be separated apart from each other in the second direction D 2 . However, this is merely exemplary, and the embodiment of the inventive concept is not limited thereto. For example, the arrangement method of the plurality of meta-material groups MG may be different from those shown above. 
     When a fluid flows through each of the meta-material groups MG, the biomaterials BM may be captured on at least some of the meta-material groups MG. Due to the biomaterials BM captured on the meta-material unit elements MU of the meta-material groups MG, the meta-material groups MG on which the biomaterials BM are captured are the biomaterials BM may have a diffraction pattern different from that of the meta-material groups (MG) having no biomaterials BM.  FIG. 16B  illustrates a diffraction pattern generated from the plurality of metal material groups MG. 
     Referring to  FIGS. 17A and 17B , in addition to those described with reference to  FIGS. 16A and 16B , a plurality of antibodies AB may be provided on at least some of the meta-material groups MG. The arrangement method of the antibodies AB may be substantially the same as described with reference to  FIG. 12A . 
     When a fluid flows through each of the meta-material groups MG, the biomaterials BM may be captured on the antibodies AB (or at least some of the meta-material groups MG) on at least some of the meta-material groups MG are meta-material unit elements MU. Due to the antibodies AB (or the biomaterials BM captured on the meta-material unit elements MU of the meta-material groups MG), the meta-material groups MG on which the biomaterials BM are captured are the biomaterials BM may have a diffraction pattern different from that of the meta-material groups (MG) having no biomaterials BM.  FIG. 17B  illustrates a diffraction pattern generated from the plurality of metal material groups MG. 
       FIG. 18  is a conceptual view for explaining a biosensor and a method for determining presence or absence of a biomaterial using the biosensor according to embodiments of the inventive concept. 
     Referring to  FIG. 18 , the biosensor according to the inventive concept may include a measuring unit  1000 , a data storage unit  2000 , a data learning unit  3000 , and a display unit  4000 . 
     The measuring unit  1000  includes a substrate  10 , an optical structure  30 , a cover  50 , and a CMOS camera or CCD camera that measures light emitted from the optical structure  30 , which are described with reference to  FIGS. 1 and 2 , and thus may measure (photograph) an emission pattern or diffraction pattern of emitted light of the biosensor. 
     The data storage unit  2000  may store data measured by the measuring unit  1000 . Specifically, the data storage unit  2000  may store data including the emission pattern or the diffraction pattern of the emitted light, which is measured by the measuring unit  1000 . 
     The data learning unit  3000  may perform machine learning through the data transmitted from the data storage unit  2000 . Specifically, the data learning unit  3000  may be trained to determine a presence or absence of the biomaterial and/or the number of biomaterials through a change in light information such as a resonance wavelength, a phase, and/or polarization of the emission patterns or diffraction patterns. 
     An algorithm of the data learning unit  3000  may be, for example, one of a neural network (NN), a convolutional neural network (CNN), a graph neural network (GNN), and a Gaussian process regression (GPR). 
     The display unit  4000  may visualize and display information such as the presence or absence of the biomaterial and/or the number of biomaterials determined by the data learning unit  3000 . 
     The biosensor according to the inventive concept may use the precise nano-optical structure having the small size without various optical components such as a light source, a spectrometer, a detector, or a filter and may easily and effectively determine the presence or absence of the biomaterial through the change in optical information such as a resonance wavelength, a phase, and/or polarization. 
     The biosensor according to the inventive concept may use the precise nano-optical structure having the small size and may easily and effectively determine the presence or absence of the biomaterial through the change in optical information such as a resonance wavelength, a phase, and/or polarization. 
     Although the embodiment of the inventive concept is described with reference to the accompanying drawings, those with ordinary skill in the technical field of the inventive concept pertains will be understood that the present disclosure can be carried out in other specific forms without changing the technical idea or essential features. Therefore, the above-disclosed embodiments are to be considered illustrative and not restrictive.