Method for manufacturing sensor substrate, sensor substrate, sensor system, and Raman scattered light detection method

Abstract

To provide a method of manufacturing a sensor substrate which is used for measuring surface-enhanced Raman scattered light and can be attached to surfaces of various objects and living bodies, and to provide the sensor substrate, sensor system, and Raman scattered light detection method.SOLUTION: A sensor system 500 is provided, comprising a sensor substrate 40 with a metal nanomesh structure attached to a surface 32 of an object or living body, a light source 502 for irradiating light toward the sensor substrate 40, and a detector 516 configured to detect surface-enhanced Raman scattered light of molecules adsorbed to the metal nanomesh structure by the irradiation of the light from the light source 502.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] The present invention relates to a method for manufacturing a sensor substrate used for measuring Raman scattered light, a sensor substrate, a sensor system, and a Raman scattered light detection method. [Background technology]

[0002] Surface-enhanced Raman spectroscopy (SERS) is a technique that enhances Raman scattering from molecules adsorbed on nanostructured metal surfaces, enabling ultra-high sensitivity measurement of molecular-level structural information. Furthermore, SERS enables non-invasive and safe measurement unaffected by the environment. Conventional SERS measurements involve dropping a sample onto metal nanoparticles coated on a substrate such as glass, and measuring Raman scattering (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Publication No. 2020-012724 Summary of the Invention [Problem to be solved by the invention]

[0004] However, conventional SERS measurements use hard substrates such as glass as the sensor substrate, which means that they cannot be attached to various curved objects or living organisms. This limits the range of applications, as it is not possible to analyze minute amounts of samples adsorbed on curved surfaces or to monitor living organisms.

[0005] The present invention has been made in view of the above-mentioned problems, and aims to provide a method for manufacturing a sensor substrate that can be attached to the surfaces of various objects and living organisms and is used to measure surface-enhanced Raman scattered light, a sensor substrate, a sensor system, and a Raman scattered light detection method. [Means for solving the problem]

[0006] The method for manufacturing a sensor substrate according to the present invention is a method for manufacturing a sensor substrate used for measuring surface-enhanced Raman scattering light, and involves producing a mesh fiber sheet made of a predetermined material by electrospinning, forming a metal layer on the mesh fiber sheet by a predetermined film formation method, and removing the mesh fiber sheet using a liquid that dissolves the predetermined material, thereby obtaining a sensor substrate with a metal nanomesh structure.

[0007] The sensor substrate according to the present invention has a metal nanomesh structure that can be attached to the surface of an object or a living body, and is used to measure surface-enhanced Raman scattering light of molecules adsorbed to the metal nanomesh structure.

[0008] The sensor system of the present invention comprises a sensor substrate having a metal nanomesh structure attached to the surface of an object or living body, a light source that irradiates light toward the sensor substrate, and a detector that detects surface-enhanced Raman scattering light of molecules adsorbed to the metal nanomesh structure when irradiated with light from the light source.

[0009] The Raman scattered light detection method of the present invention involves irradiating light from a light source onto a sensor substrate having a metal nanomesh structure attached to the surface of an object or living body, and detecting surface-enhanced Raman scattered light from molecules adsorbed to the metal nanomesh structure by the light irradiation from the light source with a detector. [Effects of the Invention]

[0010] According to the present invention, it becomes possible to detect surface-enhanced Raman scattered light by attaching a sensor substrate having a metal nanomesh structure to the surface of various objects or living organisms. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a schematic diagram showing the configuration of an electrospinning device. [Figure 2A] FIG. 1 is a schematic diagram of a mesh-like fiber sheet produced by an electrospinning device. [Figure 2B]FIG. 1 is a schematic diagram of a composite in which a metal layer is formed on a mesh-like fiber sheet. [Figure 2C] FIG. 1 is a schematic diagram of a metal nanomesh structure obtained by dissolving a mesh-like fiber sheet. [Figure 3A] This is a microscope image of a mesh-like fiber sheet made of polyvinyl alcohol (PVA). [Figure 3B] 3B is a microscope image of a composite in which a metal layer made of gold is formed on the mesh-like fiber sheet shown in FIG. 3A. [Figure 3C] 3C is a microscope image of a metal nanomesh structure obtained by removing the mesh-like fiber sheet shown in FIG. 3B with a water jet. [Figure 4] 1 is a schematic diagram showing an example in which a sensor substrate according to the present embodiment is attached to human skin. FIG. [Figure 5] 1 is a schematic diagram illustrating a configuration of a sensor system according to an embodiment of the present invention. [Figure 6] 1 is a graph showing Raman spectra of rhodamine 6G (R6G) molecules on various sensor substrates. [Figure 7A] 1 is a graph showing Raman spectra of R6G molecules on a sensor substrate at different R6G concentrations. [Figure 7B] 7B is a graph showing the relationship between the intensity of the Raman peak shown in FIG. 7A when the Raman shift is 1361 cm −1 and the R6G concentration. [Figure 8A] 10 is a graph showing Raman spectra of R6G molecules on a sensor substrate for each cycle number of a clamping test of the sensor substrate. [Figure 8B] 8B is a graph showing the relationship between the intensity of the Raman peak shown in FIG. 8A and the number of cycles of the crumpling test. [Figure 9A] 10 is a graph showing the Raman spectrum of R6G molecules on a sensor substrate for each cycle number of a stretchability test of the sensor substrate. [Figure 9B] 9B is a graph showing the relationship between the intensity of the Raman peak shown in FIG. 9A and the number of cycles in the stretchability test. DETAILED DESCRIPTION OF THE INVENTION

[0012] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described with reference to the drawings, in which the same reference numerals are used to designate the same or similar components throughout the drawings.

[0013] <Method of manufacturing sensor substrate> First, a method for manufacturing a sensor substrate used for measuring surface-enhanced Raman scattered light will be described with reference to Figures 1, 2A to 2C, and 3A to 3C. The sensor substrate according to this embodiment is manufactured mainly through the following three steps: (i) preparing a mesh-like fiber sheet; (ii) forming a metal layer; (iii) Obtaining a metal nanomesh structure.

[0014] Steps (i) to (iii) will be described in detail below.

[0015] (i) preparing a mesh-like fiber sheet; The mesh-like fiber sheet is produced by electrospinning. Figure 1 shows the configuration of an electrospinning apparatus 100 for producing the mesh-like fiber sheet. The electrospinning apparatus 100 includes a syringe 12, a nozzle 14, a high-voltage power supply 16, and a collector 18.

[0016] A solution of the material of the nanofibers 1 is inserted into the syringe 12. In this embodiment, polyvinyl alcohol (PVA) is used as the material of the nanofibers 1, but other materials such as water-soluble polymers other than PVA may be used as long as they can be used to obtain the nanofibers 1 by the electrospinning method and are soluble in liquid.

[0017] A nozzle 14 is provided at the tip of the syringe 12, and a high-voltage power supply 16 is connected to the nozzle 14. When a voltage is applied to the nozzle 14 from the high-voltage power supply 16, the PVA solution in the syringe 12 is ejected from the nozzle 14.

[0018] High-voltage power supply 16 is connected to nozzle 14 and collector 18, and applies a preset DC voltage (for example, 10 kV to 30 kV) between nozzle 14 and collector 18. Note that, although in FIG. 1, nozzle 14 is the anode and collector 18 is the cathode, the reverse may also be true.

[0019] The collector 18 is a drum-type collector that can rotate around an axis. The collector 18 is provided at a distance from the nozzle 14 so that its axial direction (longitudinal direction) is perpendicular to the longitudinal direction of the nozzle 14.

[0020] When a voltage is applied between the nozzle 14 and the collector 18 by the high-voltage power supply 16, the PVA solution is sprayed from the nozzle 14 toward the collector 18. Before the sprayed PVA solution reaches the collector 18, the solvent in the PVA solution evaporates, turning it into nanoscale fibers (nanofibers 1), and these nanofibers 1 are deposited on the surface of the collector 18. At this time, the collector 18 is rotating around its axis, and the nanofibers 1 wrap around the surface of the collector 18 and become entangled, thereby producing a mesh-like fiber sheet 3 as shown in FIG. 2A. The diameter of the nanofibers 1 constituting the mesh-like fiber sheet 3 is, for example, preferably 1 nm to 100 μm, more preferably 30 nm to 2 μm, but is not particularly limited.

[0021] Here, the syringe 12 and the nozzle 14 are movable along the axial direction of the collector 18. Therefore, by jetting the PVA solution toward the collector 18 while moving the syringe 12 and the nozzle 14 back and forth along the axial direction of the rotating collector 18 (direction H in FIG. 1), a mesh-like fiber sheet 3 with a large area can be obtained. The area of ​​the mesh-like fiber sheet 3 can be, for example, 0.01 mm 2 ~1m 2 is preferable, and 1 mm 2 ~0.04m 2 is more preferred, but is not particularly limited thereto.

[0022] Instead of the drum-type collector 18, a flat plate collector may be used.

[0023] 3A shows an image (hereinafter referred to as an SEM image) of a mesh-like fiber sheet 3 made of PVA and having a diameter of 500 nm, taken with a scanning electron microscope (SEM). The scale bar in the SEM image of FIG. 3A represents 5 μm.

[0024] (ii) forming a metal layer Next, a metal layer 5 is formed on the mesh-like fiber sheet 3 by thermal evaporation. As shown in Fig. 2B, the metal layer 5 has a semi-cylindrical shape formed in the semi-circular region of the fibers of the mesh-like fiber sheet 3. Note that the metal layer 5 may also be formed on the mesh-like fiber sheet 3 by a film formation method other than thermal evaporation.

[0025] The metal layer 5 is made of a pure metal or alloy that exhibits surface plasmon resonance. Examples of metals for the metal layer 5 include gold (Au), silver (Ag), aluminum (Al), platinum (Pt), titanium (Ti), zinc (Zn), scandium (Sc), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), indium (In), tin (Sn), yttrium (Y), zirconium (Zr), niobium (Nb), molybdenum (Mo), ruthenium (Ru), rhodium (Rh), palladium (Pd), strontium (Sr), tungsten (W), cadmium (Cd), tantalum (Ta), or alloys thereof, or indium tin oxide (ITO), indium zinc oxide (IZO), aluminum-doped zinc oxide (AZO), gallium indium zinc oxide (GIZO), zinc oxide (ZnO), or mixtures thereof. The thickness of the metal layer 5 is, for example, preferably 0.1 nm to 0.1 mm, more preferably 5 nm to 200 nm, but is not particularly limited.

[0026] Figure 3B shows an SEM image of a composite (PVA / Au composite) in which a 150 nm-thick metal layer 5 made of Au is formed on the mesh-like fiber sheet 3 of Figure 3A. The scale bar in the SEM image of Figure 3B represents 400 nm.

[0027] (iii) Obtaining a metal nanomesh structure Finally, the material of the mesh fiber sheet 3 is dissolved and the mesh fiber sheet 3 is removed using a liquid that does not dissolve the metal layer 5, thereby obtaining a metal nanomesh structure 7 consisting of a semi-cylindrical metal layer 5 as shown in Figure 2C.

[0028] For example, when removing the mesh fiber sheet 3 from the PVA / Au composite, first, water is sprayed onto the target surface (e.g., human skin), the PVA / Au composite is placed on the target surface, and then water is sprayed onto the metal layer 5, dissolving the mesh fiber sheet 3. At this time, the small amount of PVA remaining on the back side of the metal nanomesh structure 7 acts as an adhesive, allowing the metal nanomesh structure 7 to be attached to the target surface.

[0029] Here, the thickness of the metal nanomesh structure 7 is, for example, preferably 1 nm to 100 μm, more preferably 30 nm to 100 μm, but is not particularly limited. The area of ​​the metal nanomesh structure 7 is 0.01 mm, the same as that of the mesh fiber sheet 3. 2 ~1m 2 is preferable, and 1 mm 2 ~0.04m 2 However, it is not particularly limited thereto. The average density of the metal in the metal nanomesh structure 7 is 0.1 g / cm. 3 ~50g / cm 3 is preferred, and 0.1 g / cm 3 ~10g / cm 3 is more preferred, but is not particularly limited thereto.

[0030] Figure 3C shows an SEM image of a metal nanomesh structure 7 obtained by removing the mesh-like fiber sheet 3 of Figure 3B with a water jet. The scale bar of the SEM image of Figure 3C represents 400 nm.

[0031] In this way, the metal nanomesh structure 7 can realize a flexible sensor substrate for SERS, which can be attached to target surfaces of various shapes. Furthermore, the above-mentioned manufacturing method can not only manufacture large-area sensor substrates, but also sensor substrates of various shapes.

[0032] Furthermore, by setting the diameter of the mesh-like fiber sheet 3 made of PVA to approximately 500 nm and the thickness of the metal layer 5 made of Au to approximately 150 nm, the effect of localized surface plasmon resonance (LSPR) of the metal nanomesh structure 7 can be maximized.

[0033] 4 shows an example in which a flexible sensor substrate 40 is attached to human skin (forearm). By attaching the sensor substrate 40 to human skin in this way, it is possible to use a sensor system (see FIG. 5) described later to measure human sweat adsorbed on the metal nanomesh structure 7 and grasp the health condition, thereby realizing a wearable sensor that utilizes SERS.

[0034] <Sensor system configuration> Next, a sensor system for measuring Raman scattering using a sensor substrate 40 will be described with reference to Fig. 5. As shown in Fig. 5, the sensor system 500 according to this embodiment includes the sensor substrate 40 attached to the surface 32 of an object or living body, a light source 502, a mirror 504, a half mirror 506, a lens 508, a filter 510, a lens 512, a spectrometer 514, and a detector 516.

[0035] The light source 502 oscillates a continuous wave (CW) semiconductor laser of a single wavelength. Lasers of various wavelengths can be used depending on the object to be measured.

[0036] The mirror 504 reflects the incident light from the light source 502 and changes the optical axis. The light reflected by the mirror 504 is guided to the sensor substrate 40 side via a half mirror 506 and a lens 508.

[0037] The half mirror 506 transmits a part of the incident light from the light source 502. The half mirror 506 also reflects a part of the scattered light from the sensor substrate 40 (Rayleigh scattered light, Raman scattered light, etc.).

[0038] The lens 508 is located between the half mirror 506 and the sensor substrate 40, and the sensor substrate 40 is placed at the focal position of the lens 508. The lens 508 collects the transmitted light from the half mirror 506 and irradiates it toward the sensor substrate 40. When the sensor substrate 40 is irradiated with light, the scattered light from the sensor substrate 40 is collimated by the lens 508 and is incident on the half mirror 506. Specifically, surface-enhanced Raman scattered light is generated from molecules adsorbed to the metal nanomesh structure 7 of the sensor substrate 40.

[0039] The filter 510 is a notch filter that removes Rayleigh scattered light from the light reflected from the half mirror 506 and transmits Raman scattered light.

[0040] The entrance of a spectroscope 514 is disposed at the focusing position of the lens 512, and the lens 512 focuses the transmitted light (Raman scattered light) from the filter 510 onto the spectroscope 514. The spectroscope 514 disperses the light output from the lens 512.

[0041] The detector 516 is disposed on the exit side of the spectrometer 514, detects the intensity of the dispersed light from the spectrometer 514, and converts the detected intensity into an electrical signal. For example, a charge-coupled device (CCD) detector can be used as the detector 516, but is not limited to this. The detector 516 can be connected to a computer (not shown), and measurement data obtained by the detector 516 can be collected and stored by the computer.

[0042] In this way, it is possible to realize a simple configuration of the SERS sensor system 500. Furthermore, the components of the sensor system 500, except for the sensor substrate 40, can be integrated to provide a small handheld device.

[0043] Note that a configuration different from that of the sensor system 500 in FIG. 5 may be adopted as long as it is capable of measuring Raman scattered light from molecules adsorbed on the metal nanomesh structure 7 of the sensor substrate 40. For example, a dichroic mirror having wavelength-selective reflectivity may be used instead of the half mirror 506. Furthermore, a long-pass filter may be used as the filter 510 instead of a notch filter. Furthermore, a coherent Raman spectroscopy system may be adopted instead of the spontaneous Raman spectroscopy system shown in FIG. 5.

[0044] Next, measurements using sensor system 500 (Examples 1 to 4) will be described with reference to FIGS. 6 to 9B. [Example]

[0045] Raman spectra of rhodamine 6G (R6G) molecules adsorbed on various sensor substrates are shown in Figure 6. The various sensor substrates used were a silicon substrate (hereinafter referred to as a "silicon sensor substrate"), a sensor substrate with a 150 nm-thick gold film provided on a silicon substrate (hereinafter referred to as a "gold film sensor substrate"), and a sensor substrate 40 having the metal nanomesh structure 7 of this embodiment.

[0046] Using a semiconductor laser with an excitation wavelength of 785 nm and an excitation power of 2 mW, and an integration time of 20 seconds, the Raman spectrum of a 1 M R6G solution on a silicon sensor substrate was measured as the ground truth. As shown in the top graph of Figure 6, a clear Raman peak was observed.

[0047] When the excitation power was reduced to 0.2 mW and the concentration of the R6G solution was diluted to 100 nM, the Raman peaks disappeared for both the silicon sensor substrate and the gold film sensor substrate, as shown in the second and third graphs from the top in Figure 6.

[0048] On the other hand, when the Raman spectrum of the R6G molecule on the sensor substrate 40 of this embodiment is measured under the same conditions (excitation power: 0.2 mW; concentration of R6G solution: 100 nM; accumulation time: 20 seconds), as shown in the bottom graph of FIG. 6, a peak at 1185 cm -1 , 1314cm -1 , 1361cm -1 , 1509cm -1 A clear Raman peak can be observed around this range, and it can be seen that the Raman signal is enhanced compared to the ground truth, which has a higher excitation power and a higher concentration of the R6G solution.

[0049] 6, for R6G, the enhancement factor of the Raman scattering light intensity due to the metal nanomesh structure 7 of the sensor substrate 40 is (2 mW / 0.2 mW) × (1 M / 100 nM) × (8,000 / 4,500) to 10 8 It can be seen that: [Example]

[0050] Figure 7A shows the Raman spectra of R6G molecules on the sensor substrate 40 measured at different R6G concentrations. Here, the excitation wavelength of the semiconductor laser was 785 nm, the excitation power was 0.2 mW, and the integration time was 20 seconds. Figure 7B shows the Raman shift of 1361 cm in Figure 7A. -1 7A and 7B show the relationship between the Raman peak intensity and the R6G concentration at 1000 kJ / cm2. As can be seen from FIGS. 7A and 7B, the higher the R6G concentration, the stronger the Raman spectrum intensity. The minimum concentration at which a Raman peak can be detected is approximately 10 nM (=10 -8 It can be seen that M). [Example]

[0051] 8A and 8B, a flexibility test of the sensor substrate 40 will be described. The sensor substrate 40 was attached to the palm side of a glove, and a crumpling test was performed in which the sensor substrate 40 was crumpled by closing and opening the hand (see the inset in FIG. 8B).

[0052] In the clamping test, the hand was closed and opened 1000 times. Figure 8A shows the Raman spectra of the R6G molecule after 0, 10, 50, 100, 200, 500, and 1000 cycles. As shown in Figure 8A, even after 1000 cycles of clamping, the Raman spectrum remains almost unchanged, and the Raman peaks are clearly observable.

[0053] The relationship between the intensity of the four Raman peaks in Figure 8A and the number of cycles in the cramping test is shown in Figure 8B. Figure 8B shows that the intensity of the Raman peaks of the R6G molecule remains almost unchanged even after 1,000 cycles of cramping. [Example]

[0054] 9A and 9B, a stretchability test of the sensor substrate 40 will be described. The sensor substrate 40 was attached to a polydimethylsiloxane (PDMS) substrate that had been stretched by 50% in advance, and a stretchability test was performed in which the sensor substrate 40 was stretched together with the PDMS substrate and then released (see the inset in FIG. 9B).

[0055] In the stretching test, the stretching and releasing cycle was performed 1000 times. Figure 9A shows the Raman spectra of the R6G molecule after 0, 200, 400, 600, 800, and 1000 cycles. As shown in Figure 9A, even after 1000 cycles of stretching, the Raman spectrum remains almost unchanged, and clear Raman peaks can be observed.

[0056] The relationship between the intensity of the four Raman peaks in Figure 9A and the number of cycles in the stretching test is shown in Figure 9B. Figure 9B shows that the intensity of the Raman peaks of the R6G molecule hardly changes even after 1000 cycles of stretching.

[0057] As described above, the sensor substrate 40 of this embodiment can be attached to an object or a living body to observe Raman scattered light, and it is clear that the sensor substrate 40 has high flexibility, stretchability, adhesive strength, and biocompatibility.

[0058] In addition to the human arm, the sensor substrate 40 can be attached to the surfaces of various objects and living organisms to detect various test targets at low concentrations (up to 10 nM), label-free, and in situ. For example, attaching the sensor substrate 40 to a human cheek or contact lens can detect biomarkers in tears. Also, attaching the sensor substrate 40 to utility poles, masks, elevator control panels, door handles, door knobs, computer keyboards, and other surfaces can enable environmental monitoring and infection surveillance. Furthermore, attaching the sensor substrate 40 to fruits and vegetables to test for pesticides and other contaminants can ensure food safety. [Explanation of symbols]

[0059] 1. Nanofibers 3 Mesh fiber sheet 5 metal layer 7 Metal nanomesh structure 12 syringes 14 nozzles 16 High voltage power supply 18 Collector 100 Electrospinning Device 32 Surface 40 Sensor board 500 Sensor System 502 Light source 504 Mirror 506 Half Mirror 508 Lens 510 Filter 512 Lens 514 Spectrometer 516 detector

Claims

1. A method for manufacturing a sensor substrate used for measuring surface-enhanced Raman scattered light, comprising: A mesh-like fiber sheet made of a predetermined material is produced by electrospinning, forming a metal layer on the mesh-like fiber sheet by a predetermined film-forming method; The manufacturing method includes removing the mesh fiber sheet using a liquid that dissolves the predetermined material, thereby obtaining the sensor substrate with a metal nanomesh structure.

2. The method according to claim 1, wherein the diameter of the fibers constituting the mesh-like fiber sheet is 1 nm to 100 μm.

3. The area of ​​the mesh fiber sheet is 0.01 mm ２ ~1m ２ The method according to claim 1 or 2, wherein

4. The manufacturing method according to any one of claims 1 to 3, wherein the metal layer has a thickness of 0.1 nm to 0.1 mm.

5. 5. The manufacturing method according to claim 1, wherein the metal layer is made of a pure metal or alloy that exhibits surface plasmon resonance.

6. the predetermined material is polyvinyl alcohol; The manufacturing method according to any one of claims 1 to 5, wherein the metal nanomesh structure is obtained by dissolving the mesh-like fiber sheet made of polyvinyl alcohol in water.

7. A sensor substrate has a metal nanomesh structure consisting of a semi-cylindrical metal layer that can be attached to the surface of an object or living body, and is used to measure surface-enhanced Raman scattering light of molecules adsorbed to the metal nanomesh structure.

8. The sensor substrate according to claim 7, wherein the metal nanomesh structure has a thickness of 1 nm to 100 μm.

9. The area of ​​the metal nanomesh structure is 0.01 mm ２ ~1m ２ The sensor substrate according to claim 7 or 8, wherein:

10. The average density of the metal constituting the metal nanomesh structure is 0.1 g / cm ３ ~50g / cm ３ The sensor substrate according to any one of claims 7 to 9, wherein

11. The sensor substrate according to any one of claims 7 to 10, wherein the metal constituting the metal nanomesh structure is a pure metal or alloy that exhibits surface plasmon resonance.

12. A sensor substrate according to any one of claims 7 to 11 attached to a surface of an object or a living body; a light source that irradiates light toward the sensor substrate; a detector that detects surface-enhanced Raman scattered light from molecules adsorbed on the metal nanomesh structure when irradiated with light from the light source; A sensor system comprising:

13. 10. A method for detecting a metal nanomesh structure comprising: irradiating light from a light source onto the sensor substrate according to claim 7, which is attached to the surface of an object or a living body; A Raman scattered light detection method, comprising: irradiating the metal nanomesh structure with light from the light source and detecting, with a detector, surface-enhanced Raman scattered light from molecules adsorbed on the metal nanomesh structure.

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