KR20080051002A - Surface plasmon resonance sensor and system capable of absolute calibration - Google Patents

Abstract

A surface plasmon resonance sensor is provided to measure absolute changes in refractive index of an object in real time. A surface plasmon resonance imaging sensor capable of absolute calibration includes a transparent substrate(21), a first and a second prism(23A,23B), an optical system, and a light receiving unit(27). The first and the second prism are formed on one surface of the substrate symmetrically to each other about the center axis of the substrate. The optical system provides light to the first and second prisms. The light receiving unit detects the light reflected from the substrate. An SPR(Surface Plasmon Resonance) angle change of an object(28) is measured by the first prism and a refractive index change on each pixel of the object is obtained as a two-dimensional difference image by the second prism.

Description

SURFACE PLASMON RESONANCE SENSOR AND SYSTEM CAPABLE OF ABSOLUTE CALIBRATION}

The present invention relates to a Surface Plasmon Resonance (SPR) sensor, and more particularly, to a two-dimensional image angle showing a spatial refractive index change of a measurement target material obtained through a Surface Plasmon Resonance Imaging Sensor (SPR Imaging, SPRI). A surface plasmon resonance sensor capable of absolute calibration of refractive index changes in a pixel.

Surface plasmon refers to a quantized vibration mode of free electrons propagating along the surface of a metal thin film. These surface plasmons are excited by incident light incident on the metal thin film at an angle above the critical angle of the dielectric medium through a dielectric material such as a prism to cause resonance. This is called surface plasmon resonance (hereinafter SPR). The incident angle at which SPR occurs, that is, the SPR angle, is very sensitive to the change in refractive index of the material close to the metal thin film. The SPR sensor may measure quantitative analysis, qualitative analysis, thickness, or concentration of the measurement target material from the refractive index change of the material, that is, the measurement target material, that is close to the metal thin film using the above-described characteristics.

An attempt to apply SPR as a sensor was first proposed in 1982 by C. Nylander and B. Liedberg. Nylander and B. Liedberg, “Gas detection by means of surface plasmons resonance”, Sensors and Actuators 3, pp. 79-88, 1982.] Since then, SPR sensors have become one of the representative non-labeling biosensor systems that can measure the interaction of biomolecules without markers such as phosphors. Since the first commercialization of AB in 1990, it has now become the universal sensor system used by many biotech researchers (US 5641640, US 5965456).

1A is a cross-sectional view of an angle interrogated SPR sensor according to the prior art.

Referring to FIG. 1A, the angle conversion type SPR sensor according to the related art is a substrate that is optically coupled to the light transmitting substrate 11, the metal thin film 12 formed on the substrate 11, and the metal thin film 12. (11) includes a prism 13 formed below, a light source 14 for providing light to the prism 13, and a light receiving unit 15 for sensing light reflected from the substrate 11. In this case, the measurement target material 16 is positioned on the metal thin film 12.

The SPR sensor according to the related art measures the change in the SPR angle and the change in reflectivity according to the change in the angle of incident light incident on the prism 13 through the light receiving unit 15, thereby measuring any one of the materials to be measured 16. Changes in refractive index at points or pixels can be accurately measured. However, since the range for measuring the change in the refractive index is local, there is a problem in that it takes a long time to measure the change in the refractive index of the entire measurement target material 16 spatially distributed.

In order to solve this problem, the angle and wavelength of light incident in 1987 and 1988 were fixed, and two-dimensional extended incident light was used to measure the change in refractive index of the material to be measured at each pixel on the metal thin film. Surface plasmon resonance imaging sensor (SPRI) or Surface plasmon microscopy (SPM) has been proposed. and Ash, E. A, Electron Lett, 1987, 23, pp. 1091-1092, and Rothenhausler, B. and Knoll, W., Nature, 1988, 332, pp. 615-617].

Figure 1b is a cross-sectional view showing a SPRI according to the prior art.

Referring to FIG. 1B, the SPRI according to the related art includes a substrate 11, a metal thin film 12 formed on the substrate 11, and a prism 13 formed under the substrate 11 to be optically coupled to the metal thin film 12. ), A light source 14 providing light to the prism 13, and a light receiving unit 15 sensing light reflected from the substrate 11. In this case, the measurement target material 16 is positioned on the metal thin film 12.

The SPRI according to the related art expands the light provided from the light source 14 into two-dimensional parallel light and enters the prism 13, and the multi-channel capable of measuring the light reflected from the substrate 11 in units of pixels ( Multiple channel) A light receiving device such as a CCD (Charge-Coupled Device) camera can be used to measure the spatial refractive index change of the measurement target material 16 to obtain a two-dimensional image. Therefore, the change of the refractive index of the whole measurement object 16 can be measured in a short time.

SPRI according to the prior art described a method for imaging the difference image (contrast difference) according to the refractive index difference of the measurement target material 16 in each pixel on the metal thin film 12 in order to obtain a spatial refractive index change as a two-dimensional image use. In this case, the relative contrast difference according to the refractive index depends on the prism 13, the type of the metal thin film 12 (dielectric properties, dielectric properties), the thickness of the metal thin film 12, the wavelength of the light source 14 or the incident angle. Therefore, there is a problem in that the absolute change in the refractive index of each pixel of the measurement target material 16 cannot be measured.

The present invention has been proposed to solve the problems of the prior art, a surface plasmon resonance sensor that can absolutely correct the refractive index change in each pixel of the two-dimensional image showing the spatial refractive index change of the measurement target material obtained through SPRI The purpose is to provide.

Surface plasmon resonance sensor of the present invention according to an aspect for achieving the above object is a translucent substrate; A first prism and a second prism formed on one side of the substrate and formed to be symmetrical with respect to the center axis of the substrate; An optical system for providing light to the prism and a light receiving unit for sensing the light reflected from the substrate, it is possible to measure the SPR angle change of the measurement target material through the first prism, the measurement through the second prism The refractive index change in each pixel of the target material may be obtained as a two-dimensional contrast image. In this case, the first prism may be a semi-cylindrical prism, and the second prism may be a triangular prism or a trapezoid prism.

The optical system may focus the two-dimensional extended monochromatic light into the first prism and make the monochromatic light into the two-dimensional parallel light to enter the second prism.

In addition, the surface plasmon resonance sensor of the present invention may further include a metal thin film formed on the opposite surface of the substrate on which the prism is formed to be optically coupled to the prism, the metal thin film is gold (Au), silver (Ag) and It may be any one selected from the group consisting of copper (Cu).

The substrate and the prism may be formed of optical glass or optical plastic, and the prism may be formed of a material having the same refractive index as that of the substrate. In this case, the optical glass may be BK7 or SF11, and the optical plastic may be a polymethly methacrylate (PMMA), a polycarbonate ester (PC), or a cyclic olefin copolymer (Cyclic Olefin Copolymer, COC). It may be any one selected from the group consisting of.

It may further comprise an index matching oil or elastomer interposed between the substrate and the prism for optically coupling the substrate and the prism, preferably the substrate and the It is preferable to form the prism in one body.

The optical system may include a light source and a polarizer for polarizing light generated by the light source in a transverse magnetic (TM-mode). In this case, a white light having a plurality of wavelengths or a monochromatic light having a single wavelength may be used as the light source, and a laser, a light emitting diode, and a spectral filter may be used. Any one selected from the group consisting of white light provided may be used.

In addition, the optical system may further include means for arbitrarily adjusting the incident angle of the light generated from the light source, for this purpose, the optical system may further include a focusing lens for adjusting the incident angle of the light generated from the light source.

The light receiving unit may use any one selected from the group consisting of a photodiode, a photomultiplier (PMT), a charge coupled device (CCD) camera, and a photosensitive paper.

The present invention integrates an SPRI that can represent the spatial refractive index change of the measurement object in a two-dimensional image and an angle conversion type SPR sensor that can accurately measure the change in refractive index of each pixel of the measurement material in one SPR sensor, Two-dimensional image showing the refractive index change of the measurement target material obtained from the SPRI has the effect of absolute correction of the refractive index change in each pixel. This can further extend the scope of application of SPRI.

In addition, the present invention has the effect of providing a powerful means for measuring in real time the absolute change in refractive index, such as multi-channel biosensors or imaging ellipsometer.

Hereinafter, the most preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art may easily implement the technical idea of the present invention. Also in the figures, the thicknesses of layers and regions are exaggerated for clarity, and where it is said that a layer is on another layer or substrate it may be formed directly on another layer or substrate, Alternatively, a third layer may be interposed therebetween. In addition, parts denoted by the same reference numerals throughout the specification represent the same element.

The present invention discloses a means for solving the problem of SPRI that can obtain a spatial change of the refractive index of the measurement object as a two-dimensional image, that is, a problem that cannot accurately measure the change in refractive index of each pixel of the measurement material. do. To this end, the present invention is an SPRI that can measure the two-dimensional image of the spatial refractive index change of the measurement target material in one SPR sensor and an angle conversion type SPR sensor that can measure the absolute refractive index change for each pixel of the measurement target material It provides an SPR sensor that is integrated in one chip.

Figure 2a to 2b is a cross-sectional view showing the SPR sensor of the present invention, Figure 2a is an angle conversion type SPR sensor, Figure 2b shows a SPRI.

As shown in FIGS. 2A and 2B, the SPR sensor of the present invention is formed on one side of the transparent substrate 21 and the substrate 21, and the first prism is formed to be symmetrical with respect to the central axis of the substrate 21. 23A and 2nd prism 23B, the optical system which provides light to the prism 23, and the light-receiving part 27 which detects the light reflected from the board | substrate 21 is included. In addition, it may further include a metal thin film 22 formed on the opposite surface of the substrate 21 on which the prism 23 is formed to be coupled to the prism 23 to support the surface plasmon. The metal thin film 22 may be formed of any one selected from the group consisting of gold (Au), silver (Ag), and copper (Cu). In addition, a metal material such as aluminum (Al) or a semiconductor material such as germanium (Ge) It can also be formed. In this case, the measurement target material 28 is positioned on the metal thin film 22.

The prism 23 serves to increase the wave vector of incident light to excite the surface plasmon, the first prism 23A may be a semi-cylindrical prism, and the second prism 23B may be a triangular prism or It may be a trapezoidal prism.

The substrate 21 and the prism 23 have the same refractive index as each other, and may be formed of a transparent medium such as optical glass or optical plastic having a refractive index of at least 1.5. At this time, BK7 or SF11 may be used as the optical glass, and methacrylic acid metal resin (Polymethly methacrylate, PMMA), polycarbonate (PC) and cyclic olefin copolymer (Cyclic Olefin Copolymer, COC) Any one selected from the group consisting of can be used.

In addition, the SPR sensor of the present invention is an index matching oil or elastomer interposed between the substrate 21 and the prism 23 to optically couple the substrate 21 and the prism 23. ) May be further included. At this time, when the substrate 21 and the prism 23 are optically coupled using an intact matching oil or an elastomer, bubbles are generated between the substrate 21 and the prism 23 during the bonding process, or defects when used for a long time (defect) may occur. Therefore, it is preferable to form the substrate 21 and the prism 23 in one body. For example, by injection molding using an optical plastic, the substrate 21 and the prism 23 can be integrally formed.

The optical system may include a light source 24 and a polarizer 25 for polarizing light generated by the light source 24 in TM mode. In this case, white light having a plurality of wavelengths or monochromatic light having a single wavelength may be used as the light source, and any one selected from the group consisting of a laser, a light emitting diode, and white light having a spectral filter may be used. Preferably, as the light source 24, it is preferable to use monochromatic light that is easy to align optically and is inexpensive. In this case, when the light source 24 is a point light source, the light source 24 may further include a beam expander for expanding it into two-dimensional light.

The polarizer 25 serves to polarize the incident light in the TM mode in order to couple the surface plasmon wave (SPW) and the incident light which are always TM mode to each other. Therefore, the polarized light 25 should be polarized in the TM mode before the introduction of the incident light or before the light receiving part 27 is reached after the reflection of the substrate 21 so as to couple the surface plasmon wave and the incident light to each other. .

In addition, the optical system may further include means for adjusting an incident angle of light generated from the light source 24, for example, a focusing lens 26.

The light receiving unit 27 may be formed of any one selected from the group consisting of a photodiode, an optical amplifier, a CCD camera, and a photosensitive paper.

In addition, an adhesive layer formed between the substrate 21 and the metal thin film 22 may be further included to improve the adhesion between the substrate 21 and the metal thin film 22. In this case, the adhesive layer may be formed of chromium (Cr) or titanium (Ti).

 The SPR sensor according to the present invention measures the SPR angle change at each pixel of the measurement target material 28 through the first prism 23A, and measures the measurement target material 28 through the second prism 23B. The spatial refractive index change of) can be obtained as a two-dimensional image.

Hereinafter, the operation principle of the SPR sensor of the present invention will be described in detail. As mentioned above, the SPR sensor of the present invention is a two-dimensional spatial change of the refractive index of the angle conversion type SPR sensor and the measurement target material 28 that can measure the exact change in refractive index of each pixel of the measurement target material 28 Imageable SPRI is integrated into one SPR sensor.

First, an SPRI capable of measuring a two-dimensional image of a spatial refractive index change of the measurement target material 28 with reference to FIG. 2B makes the monochromatic light into two-dimensional parallel light and enters the second prism 23B to measure the measurement target material 28. ) Can be obtained as a two-dimensional image. In this case, the optical system may include a light source 24 and a polarizer 25 for polarizing light generated from the light source 24 in TM mode.

In detail, a multi-channel light receiving element, for example, may extend the light provided from the light source 24 in two dimensions to be incident on the second prism 23B and measure the light reflected from the substrate 21 on a pixel-by-pixel basis. By using a CCD camera to image the contrast difference according to the refractive index difference of the measurement target material 28 it is possible to obtain a spatial change in the refractive index of the measurement target material 28 as a two-dimensional image. In this case, the contrast difference according to the refractive index may vary depending on the prism 23, the type of the metal thin film 22, the thickness of the metal thin film 22, the wavelength of the light source 24, or the incident angle.

As such, after obtaining the change in the refractive index of the measurement target material 28 as a two-dimensional image through the second prism 23B, the substrate 21 is rotated by 180 ° based on the central axis of the substrate 21 to measure the measurement target material ( 28) is positioned above the first prism 23A. That is, the measurement target material 28 rotates the substrate 21 in a fixed state to move the positions of the first prism 23A and the second prism 23B, thereby easily switching from the SPRI to the angle-variable SPR sensor. Can be.

Next, an angle conversion type SPR sensor capable of measuring an absolute change in refractive index at each pixel of the measurement target material 28 with reference to FIG. 2A focuses two-dimensional monochromatic light and enters the first prism 23A. The absolute change in refractive index at each pixel of material 28 can be measured. At this time, the optical system is a light source 24, a polarizer 25 for polarizing the light generated from the light source 24 in the TM mode and means for arbitrarily adjusting the incident angle of the light generated from the light source 24, for example, a focusing lens ( 26). In addition, the angle conversion type SPR sensor of the present invention, unlike the angle conversion type SPR sensor according to the prior art by using a two-dimensionally extended light to measure the change in the refractive index of each pixel of the material to be measured (28) in the prior art Compared to the angle conversion type SPR sensor according to the change in refractive index at each pixel can be measured in a faster time (see Fig. 3).

Specifically, the angle conversion type SPR sensor of the present invention measures the change of the SPR angle (Δθ _SPR ) and the change in reflectance according to the change of the incident angle while adjusting the angle of incident light using the focusing lens 26. In this case, by adjusting the measured SPR angle and the change in reflectance using the Fresnel equation, it is possible to absolutely correct the change in the refractive index of each pixel of the two-dimensional image obtained by the SPRI.

The reason why the SPR angle and the reflectance change according to the incident angle is that the light energy incident on the first prism 23A has a constant angle so that the wave vector component parallel to the metal thin film 22 has the surface of the metal thin film 22. When the electron density oscillates along the interface of the measurement target material 28 that is in contact with the metal thin film 22, that is, the wave vector of the surface plasmon coincides, it is mostly absorbed by the surface plasmon, and the distribution of the plasmon field is It decreases exponentially in both directions between the interface of (22) and the measurement target material (28). Therefore, the resonance absorption condition of the plasmon is sensitively changed by the change of the refractive index of the measurement target material 28 in contact with the metal thin film 22. Due to such a change in absorption conditions, the reflectance of light is changed.

Since the angle-variable SPR sensor of the present invention measures the change in the SPR angle and the change in the reflectance according to the change in the incident angle, a means for arbitrarily adjusting the incident angle is required. Accordingly, the angle conversion type SPR sensor of the present invention uses the focusing lens 26 to adjust the angle of incidence, thereby adjusting the angle of incidence so that incident light can be incident perpendicularly to all surfaces of the prism 23 without a separate driving device. I can regulate it.

3 is a perspective view briefly showing the measuring principle of the angle conversion type SPR sensor of the present invention.

3, in the case of the angle conversion type SPR sensor of the present invention using the monochromatic light extended in two dimensions as incident light, the multiplexed SPR angle change compared to the angle conversion type SPR sensor according to the prior art (see FIG. 1A). Each channel can be measured individually and in real time. Through this, it is possible to measure the change in refractive index of each pixel of the measurement target in a faster time than the angle conversion type SPR sensor according to the prior art.

4 is a diagram illustrating a relationship between a two-dimensional image measured using an SPR sensor according to an embodiment of the present invention and a graph measured through an angle conversion type SPR sensor according to the related art shown in FIG. 1A.

Referring to FIG. 4, measurement is performed through a two-dimensional image (b) of FIG. 4 showing a spatial refractive index change of the measurement target material obtained through the SPRI of the present invention and an angle conversion type SPR sensor according to the prior art (see FIG. 1A). The relationship between a graph (a of FIG. 4) showing a change in reflectance according to one SPR angle change is shown. At this time, as shown in the figure, the change in refractive index of each channel in the measurement target material having a plurality of channels through the SPRI of the present invention can be obtained as a two-dimensional image. The line profile of each channel also corresponds to a graph of reflectance vs. SPR angle change (a in FIG. 3A).

5 is a diagram illustrating a relationship between a two-dimensional image measured using an SPR sensor according to an exemplary embodiment of the present invention and a graph of measured refractive index changes in each pixel.

Referring to FIG. 5, a graph showing a change in reflectance according to an SPR angle obtained through a two-dimensional image (b of FIG. 5) obtained through the SPRI of the present invention and an angle conversion type SPR sensor of the present invention (a of FIG. 5A). ) Shows the relationship between The relationship between the two-dimensional image obtained through the SPRI of the present invention and the sensitive refractive index change of the measurement target material present on the metal thin film obtained from the cross section can be confirmed. In the figure, "Δn" refers to a change in refractive index and "Δd" refers to a change in thickness.

As such, the present invention provides a single SPR sensor with an SPRI that can represent the spatial refractive index change of the measurement object as a two-dimensional image and an angle conversion SPR sensor that can accurately measure the change in refractive index of each pixel of the measurement material. By integrating, the refractive index change of each pixel of the image acquired through the SPRI can be absolutely corrected, thereby further extending the application range of the SPRI.

In addition, the present invention can provide a powerful means for measuring in real time the absolute change in refractive index, such as multi-channel biosensors or imaging ellipsometer.

Although the technical spirit of the present invention has been described in detail according to the above preferred embodiment, it should be noted that the above embodiment is for the purpose of description and not of limitation. In addition, those skilled in the art will appreciate that various embodiments within the scope of the technical idea of the present invention are possible.

Figure 1a is a cross-sectional view showing an angle conversion type SPR sensor according to the prior art.

Figure 1b is a cross-sectional view showing a SPRI according to the prior art.

2A to 2B are cross-sectional views showing the SPR sensor of the present invention.

Figure 3 is a perspective view showing a brief measurement principle of the angle conversion type SPR sensor of the present invention.

4 is a view showing a relationship between a two-dimensional image measured using the SPR sensor according to an embodiment of the present invention and a graph measured through the angle conversion type SPR sensor according to the prior art shown in Figure 1a.

5 is a view showing a relationship between a two-dimensional image measured using an SPR sensor according to an embodiment of the present invention and a graph of measured refractive index changes in each pixel.

*** Explanation of symbols for main parts of drawing ***

21 substrate 22 metal thin film

23 prism 24 light source

25 polarizer 26 focusing lens

27: light receiving unit 28: measurement target material

Claims (18)

Translucent substrate; A first prism and a second prism formed on one side of the substrate and formed to be symmetrical with respect to the center axis of the substrate; An optical system providing light to the prism; And It includes a light receiving unit for sensing the light reflected from the substrate, Measuring a surface plasma resonance (SPR) angle change of the measurement target material through the first prism, and obtaining a change in refractive index of each pixel of the measurement target material as a two-dimensional contrast image through the second prism. Absolute correction surface plasmon resonance sensor. The method of claim 1, And said first prism is a semi-cylindrical prism. The method according to claim 1 or 2, And said second prism is a triangular prism or a trapezoidal prism. The method of claim 1, The optical system is a surface plasmon resonance sensor for focusing a two-dimensional extended monochromatic light incident to the first prism. The method of claim 1, And said optical system makes monochromatic light into two-dimensional parallel light and makes it enter said second prism. The method of claim 1, And a metal thin film formed on the opposite side of the substrate on which the prism is optically coupled to the prism. The method of claim 6, The metal thin film is a surface plasmon resonance sensor formed of any one selected from the group consisting of gold (Au), silver (Ag) and copper (Cu). The method of claim 1, And the substrate and the prism are formed in one body. The method of claim 1, And an index matching oil or elastomer interposed between the substrate and the prism for optically coupling the substrate and the prism. The method of claim 1, The substrate and the prism is a surface plasmon resonance sensor formed of optical glass or optical plastic. The method of claim 10, The optical glass is BK7 or SF11 surface plasmon resonance sensor. The method of claim 10, The optical plastic is a surface plasmon resonance sensor of any one of metal methacrylate (PMMA), polycarbonate (PC) or cyclic olefin copolymer (Cyclic Olefin Copolymer, COC). The method of claim 1, The prism has a surface plasmon resonance sensor having the same refractive index as the substrate. The method of claim 1, The optical system, Light source; And Polarizer for polarizing the light generated from the light source to TM-mode (Transverse Magnetic) Surface plasmon resonance sensor comprising a. The method of claim 14, The light source is any one of a surface plasmon resonance sensor selected from the group consisting of a laser, a light emitting diode (light emitting diode) and a white light with a spectral filter (spectral filter). The method of claim 14, The optical system further comprises means for arbitrarily adjusting the angle of incidence of light generated from the light source. The method of claim 14, The optical system further comprises a focusing lens for adjusting the angle of incidence of light generated from the light source. The method of claim 1, The light receiver is any one selected from the group consisting of a photodiode, a photomultiplier (PMT), a charge coupled device (CCD) camera, and a photosensitive paper.

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