Plasmonic devices, optical diagnostic systems, and methods for performing single-molecule detection

Abstract

A plasmonic device, an optical diagnostic system, and a method for performing single molecule detection are provided. The plasmonic device comprises a support layer extending along a first direction and a second direction, an insulating layer on the support layer, and a plasmonic layer on the insulating layer including a cavity extending along the first direction, wherein the cavity has a three-dimensional (3D) tapered structure, propagates an electromagnetic field along the first direction and concentrates the electromagnetic field at the leading edge of the cavity, and the support layer, the insulating layer, and the plasmonic layer have an opening therein, wherein the opening is at the leading edge of the cavity and allows a target molecule of a solution present on the plasmonic layer to pass through.

Description

Technology Field

[0001] The present disclosure relates to a molecular sensing system and a method for using the same. Background Technology

[0002] The recent need for surveillance and personalized medicine is driving the development of diagnostic platforms for detecting single molecules. These diagnostic systems can be used in applications such as fluorescent antibody analysis, PCR analysis, nucleic acid amplification assays, and DNA or protein sequencing.

[0003] Currently, many of these molecular detection systems can experience long readout times due to the diffusion-limited delivery of analytes. As a result, long latency between detection events and increased background fluorescence lead to lower signal-to-noise ratios (SNR), increased errors, and reduced detection sensitivity. Furthermore, these systems generally lack the ability to provide efficient signal enhancement for a wide range of molecules for detection, such as sequencing dyes, DNA strands, or antibodies.

[0004] Therefore, a device architecture is required that can improve readout SNR and enable faster and earlier readouts for smaller sample sizes.

[0005] The foregoing description is intended only to enhance understanding of the background of the present invention and may include content that does not constitute prior art. The problem to be solved

[0006] The technical problem that the present invention aims to solve is to provide an optical diagnostic system with improved performance.

[0007] Another technical objective of the present invention is to provide a method for performing single molecule detection with improved performance. means of solving the problem

[0008] According to one aspect of the present invention for achieving the above technical problem, a plasmonic device is provided comprising a support layer extending along a first direction and a second direction, an insulating layer on the support layer, and a plasmonic layer on the insulating layer including a cavity extending along the first direction. The cavity has a three-dimensional (3D) tapered structure, propagates an electromagnetic field along the first direction, concentrates the electromagnetic field at the leading edge of the cavity, and the support layer, the insulating layer, and the plasmonic layer include an opening inside, the opening being at the leading edge of the cavity and allowing target molecules of a solution present on the plasmonic layer to pass through.

[0009] According to another aspect of the present invention for achieving the above technical problem, an optical diagnostic system comprising a plasmon device, a light source, and a detector is provided. The plasmon device comprises a support layer extending along a first direction and a second direction, an insulating layer on the support layer, and a plasmon layer on the insulating layer including a cavity extending along the first direction, wherein the cavity has a three-dimensional (3D) tapered structure, propagates an electromagnetic field along the first direction, concentrates the electromagnetic field at the leading edge of the cavity, and the support layer, the insulating layer, and the plasmon layer have an opening inside, wherein the opening is located at the leading edge of the cavity and allows target molecules of a solution present on the plasmon layer to pass through, the light source radiates excitation light to the plasmon device, and the detector detects a return signal from the plasmon device.

[0010] According to another aspect of the present invention for achieving the above technical problem, a method for performing single molecule detection is provided, comprising: providing a plasmonic device, radiating excitation light toward the plasmonic device, and detecting a return signal corresponding to a target molecule from the plasmonic device. The plasmonic device comprises a support layer extending along a first direction and a second direction, an insulating layer on the support layer, and a plasmonic layer on the insulating layer including a cavity extending along the first direction, wherein the cavity has a three-dimensional (3D) tapered structure, propagates an electromagnetic field along the first direction and concentrates the electromagnetic field at the leading edge of the cavity, and the support layer, the insulating layer, and the plasmonic layer include an opening therein, the opening being at the leading edge of the cavity and allowing a target molecule of a solution present on the plasmonic layer to pass through. Brief explanation of the drawing

[0011] The above and other features and aspects of the present invention will become more apparent from the following detailed description of exemplary embodiments thereof with reference to the accompanying drawings. FIG. 1 illustrates a schematic diagram of an optical diagnostic system according to some embodiments of the present disclosure. FIG. 2 illustrates a partial cross-sectional view of a plasmon device according to some embodiments of the present disclosure. FIG. 3a illustrates a plan view of a plasmonic device comprising a plurality of 3D cavities according to some embodiments of the present disclosure. FIG. 3b illustrates a cross-sectional view of a multi-cavity plasmonic device taken along AA according to some embodiments of the present disclosure. FIG. 4 illustrates a cross-sectional view of a plasmonic device utilizing magnetic nanofocusing for directed fluid flow according to some embodiments of the present disclosure. FIG. 5 illustrates a cross-sectional view of a plasmonic device utilizing dielectric nanofocusing for directed fluid flow according to some embodiments of the present disclosure. FIG. 6 is a flowchart illustrating the process of performing single molecule detection according to some embodiments of the present disclosure. Specific details for implementing the invention

[0012] The accompanying drawings, which illustrate embodiments of the present invention, are referenced to provide a sufficient understanding of the present invention, its advantages, and the objectives achieved by the implementation of the present invention. However, the present invention may be embodied in various different forms and should not be interpreted as being limited to the exemplary embodiments disclosed herein. Rather, these exemplary embodiments are provided to ensure that the present invention is thorough and complete and will sufficiently convey the concept of the present invention to those skilled in the art.

[0013] The present invention will be described in detail below by explaining exemplary embodiments of the invention with reference to the attached drawings. In the drawings, similar reference numerals are used throughout the drawings to refer to similar features and components.

[0014] Aspects of the present invention relate to a semiconductor-based single-molecule optical diagnostic system comprising a plasmonic device having a nanostructure having a 3D-tapered cavity having an opening at its end, which provides fluid control, concentration of target molecules, and robust optical signal enhancement for various molecular sizes. In some embodiments, one or more of passive flow, magnetic gradient, and dielectric shift are used to direct the flow of molecules on the plasmonic device for faster detection.

[0015] In some embodiments, the plasmonic device has a 3D-tapered nanopore sensor architecture with in-situ molecular concentration for optical detection of a single molecule. The plasmonic device may enable direct sample delivery to a detection hotspot using passive fluid flow through the nanopores, magnetic nanofocusing, or genomic trapping. The plasmonic device achieves direct optical enhancement at the nanopore sites to enable the visualization of a single molecule for various diagnostics, including (but not limited to) antibody and aptamer analysis, nucleic acid amplification tests (e.g., polymerase chain reaction (PCR) tests, loop-mediated isothermal amplification (LAMP) tests, etc.), and deoxyribonucleic acid (DNA) and protein sequencing.

[0016] According to some embodiments, the diagnostic system is useful for any detection method (fluorescence, Raman spectroscopy) in which a molecule is excited by light and emits an optical signal. The diagnostic system operates in a configuration where the target molecule itself can emit fluorescence when excited, where the target molecule is recognized by an antibody / binder and tagged with a fluorescent dye, or where the target has unique spectroscopic characteristics such as a Raman spectrum (not necessarily fluorescence). Since the plasmonic device focuses light (i.e., an electromagnetic field) at the sensor hotspot, any detection method that relies on light to generate an output signal can be enhanced.

[0017] FIG. 1 illustrates a schematic diagram of an optical diagnostic system (1) according to some embodiments of the present disclosure. FIG. 2 illustrates a partial cross-sectional view of a plasmon device (100) according to some embodiments of the present disclosure.

[0018] Referring to FIG. 1, as illustrated in FIG. 1, in some embodiments, an optical diagnostic system (e.g., a single molecule diagnostic system) (1) includes a light source (10), a detector (20), a controller (30), and a plasmonic device (100).

[0019] The light source (10) emits excitation light toward the plasmonic device (100) based on a control signal from the control unit (30). The plasmonic device (100) uses a cavity (e.g., a 3D tapered cavity) (110) to propagate and confine the light toward a small hot spot (120) within a well (150) of the device (100). The well (150) is configured to contain a solution containing a target molecule (132) to be detected by the diagnostic system (1), a fluorescent molecule (e.g., a fluorescent molecule) (134) that binds to the target molecule (132) and is sensitive to excitation light from the light source (10) or a direct spectroscopic signal from the target molecule (132). The fluorescent molecule (134) effectively acts as a fluorescent label for the target molecule (132). When excited by excitation light from a light source (10), the fluorescent group (134) emits a return signal (e.g., fluorescent light) that is detected by a detector (20). Then, the controller (30) determines the presence and / or concentration of the target molecule (132) in the solution based on the intensity of the signal detected by the detector (20). The controller (30) may include a processor (32) and a memory (34) local to the processor (32), and the memory (34) stores instructions thereon that cause the processor to perform processing operations of the controller (30) when executed by the processor.

[0020] In some embodiments of the present disclosure, the returned fluorescence signal is generated by a fluorescence group (134), but embodiments of the present disclosure are not limited thereto. For example, the target molecule (132) itself may emit fluorescence when excited, or the target molecule (132) may have a unique spectroscopic signature, such as a Raman spectrum (not necessarily fluorescence), which can be detected by a detector (20).

[0021] In some embodiments, the light source (10) may emit light in the visible or near-infrared wavelength range of about 400 nm to about 1200 nm. According to some embodiments, the target molecule (132) may be a target deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) strand, a protein, a peptide, a hormone (e.g., insulin), a metabolite (e.g., glucose), and other small molecules. The fluorescent dye (134) may include fluorescein, rhodamine, cyanine, bodipi-FL, 7-nitrobenz-2-oxa-1,3-diazol-4-yl, naphthalimide (Lucifer yellow), acridine orange, Alexa fluoride dye, and / or similar.

[0022] In some embodiments, a detector (20) that may include a plurality of pixel arrays provides high detection sensitivity (e.g., single-photon sensitivity) to enable the detection of single target molecules. For example, the detector (20) may include a visible wavelength photodetector, a spectrometer, a cooled infrared photodetector based on a narrowband or photopolar semiconductor, or an uncooled photodetector based on pyroelectric and ferroelectric materials, a resistive or capacitive microbolometer and / or a magnetic-based transistor. In some embodiments, the detector (20) may include a plurality of avalanche photodiodes (APD), a quantum image sensor (QIS), a plurality of single-photon avalanche diodes (SPAD), and / or others. The high detection sensitivity of the detector (20) enables the diagnostic system (1) to lower the detection threshold compared to related technology, thereby significantly reducing the detection / analysis time.

[0023] Referring to FIGS. 1 and 2, according to some embodiments, a plasmonic device (100) comprises a support layer (102) extending along a first direction (e.g., X direction) and a second direction (e.g., Y direction), an insulating layer (104) on the support layer (102), and a plasmonic layer (106) on the insulating layer (104) comprising a cavity (e.g., a nanocavity) (110) extending along the first direction. The cavity (110) has a three-dimensional (3D) tapered structure (e.g., a 3D linear tapered structure) configured to propagate an electromagnetic field generated by coupling an excitation light along the first direction (e.g., X direction) and to concentrate the electromagnetic field at the leading edge (120) of the cavity (110). The support layer (102), the insulating layer (104), and the plasmon layer (106) each have an opening (e.g., a through hole, a nanopore, or a nanoslit) (130) inside. The opening (130) may be located at the leading edge of the cavity and may function as a fluid / bioactive substance transport channel configured to allow target molecules (132) of the solution present in the well (150) of the plasmon layer (106) to pass through.

[0024] In some embodiments, the plasmon layer (106) comprises a first plasmon portion (106a) having a first thickness t1, a second plasmon portion (106b) having a second thickness t2, and a tapered plasmon portion (106t) between the first and second plasmon portions (106a, 106b), and has a tapered thickness (e.g., linear tapered / reducing thickness) and a length l1.

[0025] The cavity (110) comprises a first cavity portion (110a) having a first width (w1) and a first thickness t1, a tapered cavity portion (110t) having a width tapered along a first direction (e.g., X direction) and a thickness tapered along a third direction (e.g., Z direction), and a second cavity portion (110b) having a second width (w2) and a second thickness t2. Here, the second width (w2) is smaller than the first width (w1), and the second thickness (t2) is smaller than the first thickness (t1). The tapered cavity portion (110t) is tapered vertically along the third direction (i.e., Z direction) and tapered laterally into the nanochannel of the second cavity portion (110b) in a plane defined by the first and second directions (i.e., X and Y directions).

[0026] In some examples, the first width may be about 100 nm to about 350 nm (e.g., about 150 nm), the second width may be about 5 nm to about 25 nm (e.g., about 20 nm), the first thickness may be about 50 nm to about 300 nm (e.g., about 150 nm), the second thickness may be about 30 nm to about 200 nm (e.g., 30 nm), and the l1 length may be about 20 nm to about 1000 nm (e.g., about 500 nm). The lateral and vertical taper angles of the tapered cavity portion (110t) may be about 10° to about 25° (e.g., about 18.5°). However, embodiments of the present disclosure are not limited thereto, and any suitable values ​​for the width, thickness, length and taper angle may be assumed.

[0027] The cavity (110) acting as a waveguide may be part of a plasmonic layer (106) that exposes an insulating layer (104) in a plan view by being removed and etched, for example, by ion milling. The plasmonic layer (106) forming the sidewalls of the cavity (110) has plasmonic properties and high electrical conductivity, which allows excitation light to be efficiently captured and propagated along the length of the cavity (e.g., along the first or X direction). The plasmonic properties of the plasmonic layer (106), which may arise from coherent electron oscillations in the cavity walls traveling with the electromagnetic waves within the cavity (110), particularly generate strong photo-matter interactions at the metal-insulator interface within the edge of the cavity (110) where the conductive wall of the plasmonic layer (106) meets the insulating layer (104). Additionally, the high electrical conductivity of the plasmon layer (106) results in low ohmic loss and a larger propagation length, which enhances the propagation of the electromagnetic field along the cavity waveguide. In some examples, the plasmon layer (106) comprises gold (Au), silver (Ag), aluminum (Al), gallium nitride (GaN), and / or similar materials. The choice of material for the plasmon layer (106) is closely related to the wavelength of the excitation light, as each material can efficiently combine and limit light within a specific wavelength range. For example, an excitation wavelength of about 750 nm or a near-infrared (NIR) wavelength may be suitable for a plasmon layer (106) made of gold or gallium nitride, whereas a wavelength of about 400 nm to about 550 nm may be more suitable for a plasmon layer (106) made of aluminum or silver.

[0028] According to some embodiments, the 3D-tapered structure (and in particular, the taper angle) of the tapered cavity portion (110t) provides improved (e.g., optimal) lateral confinement of the electromagnetic field, thereby enabling light captured by the wider first cavity portion (110a) to be efficiently focused into the narrow nanochannel of the second cavity portion (110b). The length of the second cavity portion (110b) is designed to ensure strong light enhancement (i.e., strong confinement of surface-plasmon-polariton (SPP) modes) at the leading edge (120) where the opening (130) is located. Thus, the cavity (110) creates a sensor hotspot with high and uniform electromagnetic field strength at the opening (130). Consequently, as long as the target molecule can pass through the aperture (130), the return optical signal (e.g., fluorescence, vibrational spectrum, or spectroscopic signal) will experience a strong boost, which leads to a high signal-to-noise ratio (SNR) of the optical readout.

[0029] In some embodiments, an opening (130) created in the plasmon, insulating, and supporting layers (106, 104, and 102) enables passive flow of the solution through the sensor hotspot (i.e., 120 / 130) and enables concentration of the target molecule (132) at the sensor hotspot (i.e., 120 / 130). Because the material of the plasmon layer (106) (e.g., gold) is hydrophobic and the materials of the insulating layer (e.g., silica) and the supporting layer (102) (e.g., silicon nitride) are hydrophilic, a surface tension gradient is created on the inner wall of the opening (130), which attracts the liquid toward the opening (130) and causes it to pass through the opening (130). Additionally, the evaporation of fluid at the bottom of the opening (130) (near the support layer (102)) draws additional fluid from the top of the opening (130) (near the plasmon layer (106)). However, the evaporation process may be slower and less dominant than the surface tension gradient phenomenon described above. By passively directing the target molecule (132) to the plasmon hotspot of the opening (130), the plasmon device (100) enables rapid detection of molecules diffusing into the solution at sub-micromolar concentrations.

[0030] In some examples, the absorbent layer (108) may be positioned below a support layer (102) capable of absorbing fluid leaving the opening (130), thereby allowing more fluid to flow and enabling target molecules (132) to be better collected at the opening (130). The absorbent layer (108) may comprise absorbent cellulose, sodium polyacrylate, and / or similar materials. However, embodiments of the present invention are not limited to utilizing absorbent layers, and in some embodiments, voids may exist below the opening (130) instead of absorbent layers.

[0031] In some embodiments, the aperture (130) may be a through hole (e.g., a nanopore) or a nanoslit slightly larger than the target molecule, which enhances (e.g., maximizes) the interaction (e.g., binding) of the target molecule at the inner wall of the aperture (130). This enables the diagnostic system (1) to perform single-molecule detection with a high SNR, along with an enhanced optical signal from the molecule at the plasmonic hotspot (i.e., the aperture (130)). In some examples, the aperture (130) may have a width of about 5 nm to about 25 nm. According to some examples, the volumetric limit of the 20 nm aperture allows the single plasmonic device (100) to detect a wide variety of target molecules, such as single DNA strands, antibodies, protein molecules, etc., which are generally smaller than 20 nm in size. Here, if the opening (130) is too wide relative to the size of the target molecule, the electromagnetic field strength may decrease near the center of the opening, resulting in a weak non-uniform electric field strength, and the target molecule may have less interaction with the opening walls and flow through the opening faster, all of which may result in a weaker optical reading (e.g., a weak fluorescence or spectroscopic signal) and a lower SNR.

[0032] According to some embodiments, the support layer (102) provides the stiffness and structural support necessary to create a stable, thin, and freely suspended (e.g., cantilevered) nanophotonic structure so that when the plasmonic device is milled at the tip (120), both sides of the created opening (130) are open. In some examples, the second plasmonic part (106b) may be about 100 nm thick, the insulating layer (104) may be about 200 nm thick, and the support layer may be about 100 nm to about 500 nm thick. Thus, the opening may have a length of less than a micron (e.g., along the Z direction). Without the added stiffness of the support layer, it may be impossible to drill an opening / nanopore of this aspect ratio using a traditional milling method without breaking or deforming the plasmonic device at the tip (120). For example, it can be very difficult to make a 20 nm wide hole through a 500 μm thick silicon wafer compared to a 200 nm thick silicon nitride membrane.

[0033] The layers of the plasmonic device (100) can be fabricated on a silicon substrate (109). Not only is it readily available at a low cost, but the atomic layer flatness of the silicon substrate also allows for the fabrication of layers exhibiting atomic layer flatness.

[0034] FIGS. 1 and 2 illustrate an embodiment in which the plasmonic device (100) includes a single 3D tapered cavity, but the embodiments of the present disclosure are not limited thereto.

[0035] FIG. 3a illustrates a plan view of a plasmonic device (100-1) comprising a plurality of 3D cavities according to some embodiments of the present disclosure. FIG. 3b illustrates a cross-sectional view of a plasmonic device (100-1) taken along AA according to some embodiments of the present disclosure.

[0036] In some embodiments, a plurality of cavities (e.g., 110-1 to 110-4) may concentrate the excitation light onto a single aperture (130) to further increase the intensity and uniformity of the electromagnetic field at the aperture (130). This arrangement may produce a higher SNR than embodiments comprising a single cavity (110). FIG. 3a illustrates four concentric cavities symmetrically arranged around the aperture (130), but embodiments of the present disclosure are not limited thereto, and the plasmonic device (100-1) may include any suitable number of cavities.

[0037] The plasmonic devices (100 and FIG. 100-1) of the embodiments of FIG. 1 to 3b utilize passive molecular concentration at a sensor hotspot, but the embodiments of the present disclosure are not limited thereto. For example, the plasmonic device may utilize magnetic nanofocusing or dielectric trapping to actively concentrate target molecules at a sensor hotspot.

[0038] FIG. 4 illustrates a cross-sectional view of a plasmonic device (100-2) utilizing magnetic nanofocusing for directed fluid flow according to some embodiments of the present disclosure. The plasmonic device (100-2) is substantially identical to the plasmonic device (100) except for the use of a support layer (102-2), a substrate (109-2), a magnetic source (200), and a magnetic fluorescent group (134-2). For brevity, the following description will focus primarily on the differences between the plasmonic device (100) and the plasmonic device (100-2) described above with reference to FIG. 1 to 3b.

[0039] In some embodiments, the plasmonic device (100-2) utilizes magnetic nanofocusing to actively focus a target molecule (132) at a plasmonic hotspot (i.e., an opening (130)). In these embodiments, the fluorophore (134-2) comprises magnetic beads that are sensitive and movable in the presence of a magnetic field gradient. The magnetic fluorophore (134-2) may comprise plastic or silica beads having a magnetic core, which have molecular acceptors on their outer surface capable of binding to the target molecule (132).

[0040] According to some embodiments, the plasmonic device (100-2) includes a magnetic source (200) that generates a magnetic field at the location of the opening (130). Additionally, the support layer (102-2) includes one or more ferromagnetic materials, such as nickel, cobalt, and iron, which serve to strengthen the magnetic field at the opening (130). Due to the sharp spatial gradient at the opening (130) at the edge of the 3D taper of the plasmonic layer (106), the application of a uniform magnetic field to the hotspot region generates a strong magnetic field at the opening (130). The strong magnetic field rapidly directs the target molecule (132) captured on the magnetophore (134-2) toward the opening (130) and concentrates the molecule (132) at the sensor hotspot. As a result, the diagnostic system can perform rapid on-chip detection of a single molecule with a high SNR.

[0041] Here, the substrate (e.g., silicon substrate) (109-2) can extend along the lower part of the support layer (102-2) to cover the lower part of the opening (130).

[0042] FIG. 5 illustrates a cross-sectional view of a plasmonic device (100-3) utilizing dielectric nanofocusing for directed fluid flow according to some embodiments of the present disclosure. The plasmonic device (100-3) is substantially identical to the plasmonic device (100) except for first and second portions (106-3, 106-4) of an electrically insulated plasmonic layer, a support layer (102-3), and an alternating current (AC) source (210). For brevity, the following description will focus primarily on the differences between the plasmonic device (100-3) and the plasmonic device described above with reference to FIG. 1 through 3b.

[0043] In some embodiments, the plasmonic device (100-3) utilizes dielectric transport to transport the target molecule (132) toward the opening (130) to enhance molecular fluorescence and detection of the target molecule (132). In these embodiments, the plasmonic layer (106) is divided into two electrically insulated portions (106-3 and 106-4). An alternating current (AC) source (210) applies an AC voltage across the two portions (106-3 and 106-4), which induces an AC electric field across the opening (130) (e.g., a nanogap), causing a strong gradient electric force to be generated in the gap (i.e., the opening (130)). The non-uniform electric field near the opening (130) exerts a force on the target molecule (132), directing it toward the opening (130) and concentrating the molecule (132) at the sensor hotspot. As a result, the diagnostic system can perform rapid on-chip detection of single molecules with high SNR.

[0044] Here, the support layer (102-3) may be a substrate (e.g., a silicon substrate) (102-3) that extends along the lower surface of the insulating layer (104) and covers the bottom of the opening (130).

[0045] FIG. 6 is a flowchart illustrating a process (600) for performing single molecule detection according to some embodiments of the present disclosure.

[0046] In some embodiments, a plasmonic device (100) is provided, comprising a support layer (102) extending along a first direction (e.g., X direction) and a second direction (e.g., Y direction), an insulating layer (104) on the support layer (102), and a plasmonic layer (106) on the insulating layer (104) (S602). The plasmonic layer (106) comprises a cavity (110) extending along the first direction, which has a three-dimensional (3D) tapered structure and is configured to propagate an electromagnetic field along the first direction and concentrate the electromagnetic field at the leading edge of the cavity. In some embodiments, the support layer (102), the insulating layer (104), and the plasmonic layer (106) together comprise an internal opening (130) located at the leading edge of the cavity (110) and configured to allow a target molecule (132) of the solution present in the well (150) of the plasmonic layer (106) to pass through.

[0047] In some embodiments, the control unit (30) transmits a control signal to the light source (10) to radiate the excitation light toward the plasmon device (100) (S604), and the detection unit (20) detects a return signal corresponding to a target molecule from the plasmon device (100) and transmits the signal to the control unit (30) for processing (S606).

[0048] Accordingly, as described above, embodiments of the present disclosure provide a single-molecule diagnostic system comprising a nanoplasmonic device capable of providing optical enhancement at a sensor hotspot and also focusing target molecules at the hotspot, resulting in rapid readings with a high SNR. The plasmonic device can use a 3D tapered cavity with an opening at the end to efficiently couple excitation light and trap light at the opening site. The plasmonic device can also guide the flow of target molecules into the opening through passive fluid flow, magnetic nano-trapping, or genomic trapping. This enables the optical diagnostic system to visualize single molecules for various diagnostics, including but not limited to antibody and aptamer analysis, NAAT tests (PCR or LAMP), DNA and protein sequencing, and / or similar methods.

[0049] Although the present disclosure has been described in detail according to the embodiments, the embodiments described herein do not limit the scope of the present disclosure to the form of the embodiments. Those skilled in the art to which the present invention pertains will understand that changes and modifications to the described structure and method of assembly and operation may be made as described in the following claims and equivalents without departing from the principles and scope of the present invention.

[0050] Although terms such as “first,” “second,” “third,” etc., may be used herein to describe various components, components, and / or sections, these components, components, and / or sections should not be limited by these terms. These terms are used to distinguish one element, component, or section from another element, component, or section. Accordingly, the first component, component, or section discussed above may be referred to as the second component, component, or section without departing from the spirit and scope of the invention.

[0051] Spatially relative terms used herein encompass different orientations of the device in use or operation in addition to the orientations depicted in the drawings. The device may be oriented differently (e.g., rotated 90 degrees or in other orientations), and spatially relative descriptors used in this disclosure should be interpreted accordingly. Additionally, when a layer is referred to as being "between" two layers, it may be the only layer between the two layers, or one or more intermediate layers may also be present.

[0052] The terms used herein are intended to describe specific embodiments and are not intended to limit the invention. As used herein, the singular forms “a” and “an” are intended to include the plural forms unless the context clearly indicates otherwise. Additionally, as used herein, the terms “comprising” and / or “comprising” are to be understood to specify the presence of the mentioned features, numbers, steps, actions, elements, and / or components, but not to exclude the presence or addition of one or more other features, numbers, steps, actions, elements, components, and / or groups thereof. As used herein, the term “and / or” includes any and all combinations of one or more of the associated enumerated items. Furthermore, when describing embodiments of the invention, the use of “may” refers to “one or more embodiments of the invention.” Additionally, the term “exemplary” is intended to refer to an example or illustration.

[0053] When an element or component is referred to as being "connected" or "combined" to another element or component, it may be directly connected or combined to the other element or component, or one or more intermediate components may exist. When an element or layer is referred to as being "directly connected" or "directly combined" to another element or component, no intervening element or component exists.

[0054] As used herein, the terms "substantially," "approximately," and similar terms are used as terms of approximation rather than of degree, and are intended to describe inherent variations in measured or calculated values ​​that may be recognized by a person skilled in the art.

[0055] As used herein, the terms "use" and "using" may be considered synonyms for the terms "utilize" and "utilizing," respectively.

[0056] Additionally, any numerical range cited herein is intended to include all sub-ranges of the same numerical precision contained within the cited range. For example, the range “1.0 to 10.0” is intended to include all sub-ranges between (and including) the cited minimum value 1.0 and the cited maximum value 10.0, i.e., having a minimum value greater than or equal to 1.0 and a maximum value less than or equal to 10.0, for example, from 2.4 to 7.6. Any maximum numerical limit cited herein is intended to include all lower numerical limits contained therein, and any minimum numerical limit cited herein is intended to include all higher numerical limits contained therein. Accordingly, the applicant reserves the right to explicitly cite any sub-range contained within the range explicitly cited herein by modifying the specification, including claims. All of these scopes are intended to be described in this specification in such a way that modifications to explicitly cite these sub-scopes comply with the requirements of 35 USC § 112, first paragraph and 35 USC § 132(a).

[0057] Controllers and / or any other related devices or components according to the embodiments described herein may be implemented by using any suitable hardware, firmware (e.g., application-specific integrated circuit), software, or a suitable combination of software, firmware, and hardware. For example, various components of the controller may be formed on a single integrated circuit (IC) chip or on separate IC chips. Additionally, various components of the controller may be implemented on a flexible printed circuit film, a tape carrier package (TCP), or a printed circuit board (PCB), or formed on the same substrate. Furthermore, various components of the controller may be processes or threads that execute on one or more processors and, on one or more computing devices, execute computer program instructions and interact with other system components to perform the various functions described herein. Computer program instructions are stored in memory that may be implemented in a computing device using a standard memory device, such as, for example, random access memory (RAM). Computer program instructions may also be stored in other non-transient computer-readable media, such as, for example, a CD-ROM or a flash drive. In addition, those skilled in the art should recognize that the functions of various computing devices may be combined or integrated into a single computing device, or that the functions of a specific computing device may be distributed across one or more other computing devices without departing from the scope of the exemplary embodiments of the present invention.

[0058] Although the present disclosure has been described in detail according to the embodiments, the embodiments described herein do not limit the scope of the present disclosure to the form of the embodiments. Those skilled in the art to which the present invention pertains will understand that changes and modifications to the described structure and method of assembly and operation may be made as described in the following claims and equivalents without departing from the principles and scope of the present invention.

Claims

Claim 1 A plasmon device comprising: a support layer extending along a first direction and a second direction; an insulating layer on the support layer; and a plasmon layer on the insulating layer including a cavity extending along the first direction, wherein the cavity has a three-dimensional (3D) tapered structure, propagates an electromagnetic field along the first direction, concentrates the electromagnetic field at the leading edge of the cavity, and wherein the support layer, the insulating layer, and the plasmon layer include an opening therein, the opening being at the leading edge of the cavity, and passes a target molecule of a solution present on the plasmon layer. Claim 2 In claim 1, the cavity is a plasmonic device that exposes the insulating layer in a plan view. Claim 3 In claim 1, the cavity comprises: a first cavity portion having a first width and a first thickness; a tapered cavity portion having a width tapered along the first direction and a thickness tapered along a third direction intersecting the first and second directions; and a second cavity portion having a second width and a second thickness, wherein the leading edge of the cavity is at the end of the second cavity portion. Claim 4 In claim 3, the plasmon layer comprises a first plasmon part having the first thickness; a second plasmon part having the second thickness; and a tapered plasmon part having a tapered thickness located between the first and second plasmon parts. Claim 5 In paragraph 4, the tapered plasmon part is a plasmon device tapered along a third direction. Claim 6 A plasmon device according to paragraph 3, wherein the second width is smaller than the first width and the second thickness is smaller than the first thickness. Claim 7 A plasmon device according to claim 1, wherein the plasmon layer comprises a hydrophobic material and the insulating layer comprises a hydrophilic material, and the insulating layer attracts a fluid present on the plasmon layer into the opening. Claim 8 A plasmon device according to claim 1, wherein the plasmon layer comprises gold, the insulating layer comprises silica, and the supporting layer comprises silicon nitride. Claim 9 In claim 1, the support layer provides structural support to the plasmon layer and the insulating layer to create a free-hanging structure with both sides of the opening open, and the plasmon device further comprises an absorption layer below the support layer, and the absorption layer absorbs fluid leaving the bottom of the opening. Claim 10 A plasmonic device according to claim 1, wherein the opening is a fluid channel that enables passive flow of a solution through at least one of evaporation and a surface tension gradient and concentration of target molecules of the solution at the opening. Claim 11 In claim 1, the opening is a plasmonic device having a width of 5 nm to 25 nm. Claim 12 A plasmon device according to claim 1, wherein the plasmon layer comprises gold, the insulating layer comprises silica, and the supporting layer comprises a ferromagnetic material comprising at least one of nickel, iron, and cobalt. Claim 13 A plasmon device according to claim 12, further comprising a substrate below the support layer, wherein the opening exposes the upper surface of the substrate in a plan view. Claim 14 A plasmonic device according to claim 12, wherein the solution comprises a target molecule bound to a magnetic nanoparticle, and the opening enables concentration of the target molecule of the solution at the opening by attracting the magnetic nanoparticle toward a portion of the support exposed by the opening. Claim 15 A plasmon device according to claim 1, wherein the plasmon layer comprises a first portion and a second portion, the first portion comprises a first plasmon portion having a first thickness; a second plasmon portion having a second thickness; and a tapered plasmon portion having a tapered thickness located between the first and second plasmon portions, the second portion is electrically insulated from the first portion, the opening is a transvese gap physically separating the first portion and the second portion of the plasmon layer, and the support layer is a substrate comprising the bottom of the transvese gap. Claim 16 A plasmonic device according to claim 15 in which target molecules in a solution are directed toward an opening through dielectric migration in the presence of an alternating (AC) electric field across a transverse gap. Claim 17 An optical diagnostic system comprising a plasmon device, a light source, and a detector, wherein the plasmon device comprises: a support layer extending along a first direction and a second direction; an insulating layer on the support layer; and a plasmon layer on the insulating layer including a cavity extending along the first direction, wherein the cavity has a three-dimensional (3D) tapered structure, propagates an electromagnetic field along the first direction, concentrates the electromagnetic field at the leading edge of the cavity, wherein the support layer, the insulating layer, and the plasmon layer have an opening therein, wherein the opening is located at the leading edge of the cavity and allows target molecules of a solution present on the plasmon layer to pass through, wherein the light source emits excitation light to the plasmon device, and the detector detects a return signal from the plasmon device. Claim 18 An optical diagnostic system according to claim 17, wherein the return signal is a fluorescent signal or spectral signal emitted by a fluorescent group bound to a target molecule in a solution in response to excitation by excitation light. Claim 19 An optical diagnostic system according to claim 17, wherein the cavity is tapered laterally and vertically, and the opening is a fluid channel that enables passive flow of a solution through at least one of evaporation and a surface tension gradient and concentration of target molecules of the solution at the opening. Claim 20 A method for performing single molecule detection by passing a target molecule in a solution present on the plasmon layer, comprising: providing a plasmon device, radiating excitation light toward the plasmon device, and detecting a return signal corresponding to a target molecule from the plasmon device, wherein the plasmon device comprises: a support layer extending along a first direction and a second direction; an insulating layer on the support layer; and a plasmon layer on the insulating layer including a cavity extending along the first direction, wherein the cavity has a three-dimensional (3D) tapered structure, propagates an electromagnetic field along the first direction and concentrates the electromagnetic field at the leading edge of the cavity, wherein the support layer, the insulating layer, and the plasmon layer include an opening therein, the opening being at the leading edge of the cavity.

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