CN103018211B - Analysis apparatus and manufacturing method for sensor chip thereof - Google Patents
Analysis apparatus and manufacturing method for sensor chip thereof Download PDFInfo
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- CN103018211B CN103018211B CN201210480083.XA CN201210480083A CN103018211B CN 103018211 B CN103018211 B CN 103018211B CN 201210480083 A CN201210480083 A CN 201210480083A CN 103018211 B CN103018211 B CN 103018211B
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Abstract
The invention provides an analysis apparatus and a method for manufacturing a sensor chip in the analysis apparatus. The analysis apparatus includes the sensor chip; a light source for generating laser; a collimation lens for changing the laser into parallel light; a polarized light control element enabling the parallel light to pass; a light detector for detecting the light obtained through the sensor chip; an objective lens for converging scattered light in the sensor chip; and a beam splitter for guiding passing the polarized light control element to the sensor chip and guiding the scattered light in the sensor chip to the objective lens. The sensor chip includes: a glass substrate that has a planar portion; and a diffraction grating, on which a target substance is placed, that includes a plurality of first protrusions periodically arranged in a period equal to or greater than 100 nm and equal to or less than 1000 nm in a first direction that is parallel to the planar portion, a base portion that is formed by the planar portion of the glass substrate in a region of the adjacent first protrusions, and a plurality of second protrusions that is formed on upper faces of the plurality of the first protrusions and forming overlap construction with the first protrusions.
Description
The application is the divisional application that the application number submitted on November 18th, 2010 is 201010551069.5, denomination of invention is the patented claim of " sensor chip, sensor box and analytical equipment ".
Technical field
The present invention relates to the manufacture method of the sensor chip in analytical equipment and analytical equipment.
Background technology
In recent years, the demand of the sensor used along with medical diagnosis and Food Inspection etc. constantly increases, and needs to develop small-sized and can the sensor technology of sensing detection fast.For meeting these demands, carry out the research of all types of sensors headed by electrochemical method.Wherein, consider integrated, low cost, need not select to measure the factors such as environment, the sensor of application surface plasma resonance (SPR:SurfacePlasmon Resonance) technology is shown great attention to.
Here, so-called surface plasma refers to the electron waves vibration mode being caused optically-coupled by the boundary condition that surface is intrinsic.As the method for excitating surface plasma, there is following method: carve diffraction grating in metal surface, make the method that light is combined with plasma; And utilize the method for evanescent wave.Such as, as the structure of sensor utilizing SPR, following structure is known to: it metal film comprising total reflection prism, contact with the target substance formed on the surface of this prism.The absorption with or without target substance is detected, such as, with or without the Antigen adsorption etc. during antigen-antibody reaction by this structure.
But metal surface exists mode transmission surface plasma, on the other hand, metal particle also exists the surface plasma of local type.When the surface plasma that on the microtexture of the known surface plasma in local type, i.e. surface, local exists is excited, the electric field having and significantly strengthen can be responded to.
Therefore, for the purpose of the sensitivity improving sensor, propose a kind of sensor (LSPR:Localized SurfacePlasmon Resonance) utilizing the surface plasmon resonance of metal particle and metal Nano structure.Such as, record in patent documentation 1 (Japanese Unexamined Patent Publication 2000-356587 publication) and penetrate metal particle is carried out illumination with the membranaceous transparency carrier being fixed on surface, detect media variations near metal particle by measuring through the absorbance of the light of metal particle, and detect absorption and the accumulation of target substance.
But, in patent documentation 1, prepare equably metal particle size (size and shape) and regularly arrange metal particle be very difficult.If can not control size and the arrangement of metal particle, then absorbing wavelength and the resonant wavelength of generation of resonating can produce error.So, the width of absorbance spectrum just broadens, peak strength step-down.Therefore, the signal intensity for detecting the media variations near metal particle reduces, even if it is also limited to improve transducer sensitivity.Therefore, just insufficient for the sensitivity according to sensor during absorbance spectrum designated substance.
Summary of the invention
The present invention in view of the above problems, its object is to provide a kind of sensitivity improving sensor, can according to the sensor chip of raman spectroscopy spectrum intended target material, sensor box and analytical equipment.
In order to solve the problem, the present invention adopts following structure.
The sensor chip of first aspect present invention comprises: matrix part, has planar portions; And diffraction grating, there is the surface formed by metal, be formed in described planar portions, and target substance is configured on described diffraction grating, described diffraction grating comprises: multiple first projection, along the first direction parallel with described planar portions, arrange with being less than or equal to the cycle of 1000nm by being more than or equal to 100nm; Multiple base part, between adjacent two described first projections, forms the bottom of described matrix part; And multiple second projection, be formed in the upper surface of multiple described first projection.
According to a first aspect of the invention, what strengthened according to surface plasma resonance (surfaceplasmon resonance) by the first projection closely connects the surface excitation of electric field to similar shape, further by showing the high Surface enhanced raman spectroscopy of enhancing degree (SERS:Surface Enhanced Raman Scattering) based on the metal superfine structure of the second projection.Specifically, if to being formed with multiple first raised and multiple second raised face incident ray, then can produce based on the intrinsic vibration mode (surface plasma) in the surface of multiple first projection.So along with the vibration of light, free electron resonates, and along with the vibration of free electron, electromagnetic vibration is excited.Because of the vibration of this electromagnetic vibration effect free electron, so form system, the so-called surface plasma excimer (SPP:Surface Plasmon Polariton) of both combinations vibration.Thus, near multiple second projection, localized surface plasmons resonance (LSPR:Localized SurfacePlasmon Resonance) is excited.In this configuration, because the distance between adjacent two the second projections is little, therefore, near this contact, extremely strong enhancing electric field is produced.Further, if adsorb one to several target substance on this contact, then SERS can be there is.Therefore, intrinsic sharp-pointed SERS spectrum can be obtained in target substance.Therefore, can provide a kind of and improve transducer sensitivity and according to the sensor chip of SERS spectrum intended target material.In addition, by suitably changing the height of cycle of the first projection and height, the second projection, thus any wavelength of the location matches of resonance peak can be made.Therefore, suitably can select the wavelength of the light irradiated when intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described first projection periodically arranges along second direction that is parallel with described planar portions, that intersect with described first direction.Like this, with only have along the direction (first direction) parallel with the planar portions of matrix material periodically form the first projection situation compared with, sensing detection can be carried out under wider resonant condition.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material.Further, except suitably can changing the cycle of the first direction of the first projection, the cycle of second direction can also suitably be changed.Therefore, the wavelength of the light irradiated when suitably can change intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described second projection periodically arranges along the third direction parallel with described planar portions.Like this, the cycle of the second projection can suitably be changed.Therefore, the wavelength of the light irradiated when suitably can change intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described second projection periodically arranges along fourth direction that is parallel with described planar portions, that intersect with described third direction.Like this, the direction (third direction) parallel with the planar portions of matrix material with only edge is formed compared with the situation of the second projection, can carry out sensing detection under wider resonant condition.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material.Further, except the cycle that can suitably change on the third direction of the second projection, the cycle in fourth direction can also suitably be changed.Therefore, the wavelength of the light irradiated when suitably can change intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described second projection is made up of particulate.Like this, can provide a kind of and improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material.
In sensor chip of the present invention, preferably when the width of the first projection on described first direction is set to W1, when the distance between adjacent two described first projections on described first direction is set to W2, meet the relation of W1 > W2.Like this, owing to exciting the space filling factor of first projection of LSPR to increase, therefore with meet W1 < W2 relation situation compared with, sensing detection can be carried out under wider plasma resonance condition.And, irradiate the energy of light when can effectively utilize intended target material.
In sensor chip of the present invention, the ratio of the described distance W2 between adjacent two described first projections on the described width W 1 of described first projection on preferred described first direction and described first direction meets the relation of W1:W2=9:1.Like this, sensing detection can be carried out under wider plasma resonance condition.And, irradiate the energy of light when can effectively utilize intended target material.
In sensor chip of the present invention, the metal preferably forming the described surface of described diffraction grating is gold or silver-colored.Like this, because gold or silver have the characteristic showing SPP, LSPR, SERS, therefore can show SPP, LSPR, SERS easily, thus target substance can be detected in high sensitivity.
The sensor box of second aspect present invention comprises: the sensor chip of above-mentioned record; Delivery section, for being transported to described target substance on the surface of described sensor chip; Mounting portion, for loading described sensor chip; Housing, for accommodating described sensor chip, described delivery section and described mounting portion; And illumination window, be arranged on the position relative with the surface of described sensor chip of described housing.
According to a second aspect of the invention, because have the sensor chip of above-mentioned record, so optionally light splitting Raman diffused light, and target molecule can be detected.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor box of SERS spectrum intended target material.
The analytical equipment of third aspect present invention comprises: the sensor chip of above-mentioned record; Light source, for irradiating light to described sensor chip; And photodetector, for detecting the light obtained by described sensor chip.
According to a third aspect of the invention we, because have the sensor chip of above-mentioned record, so optionally light splitting Raman diffused light, and target molecule can be detected.Therefore, can provide a kind of and improve transducer sensitivity and can according to the analytical equipment of SERS spectrum intended target material.
The sensor chip of fourth aspect present invention comprises: matrix part, has planar portions, and diffraction grating, there is the synthesising pattern by the first concaveconvex shape and the second concaveconvex shape overlap being formed in described planar portions, described diffraction grating has the surface formed by metal, and target substance is configured on described diffraction grating, wherein, in described first concaveconvex shape, multiple first convex form is arranged with being less than or equal to the cycle of 1000nm by being more than or equal to 100nm, in described second concaveconvex shape, multiple second convex form is arranged on multiple described first convex form by the cycle shorter than the cycle of described first concaveconvex shape.
According to a forth aspect of the invention, what strengthened according to surface plasma resonance (surface plasmon resonance) by the first convex form closely connects the surface excitation of electric field to similar shape, further by showing the high Surface enhanced raman spectroscopy of enhancing degree (SERS:Surface Enhanced Raman Scattering) based on the metal superfine structure of the second convex form.Specifically, if to the face incident ray being formed with the first concaveconvex shape and the second concaveconvex shape, then can produce based on the intrinsic vibration mode (surface plasma) in the surface of multiple first concaveconvex shape.So along with the vibration of light, free electron resonates, and along with the vibration of free electron, electromagnetic vibration is excited.Because of the vibration of this electromagnetic vibration effect free electron, so form system, the so-called surface plasma excimer (SPP:Surface Plasmon Polariton) of both combinations vibration.Thus, near the second concaveconvex shape, localized surface plasmons resonance (LSPR:LocalizedSurface Plasmon Resonance) is excited.In this configuration, because the distance between adjacent two the second convex forms is little, therefore, near this contact, extremely strong enhancing electric field is produced.Further, if adsorb one to several target substance on this contact, then SERS can be there is.Therefore, intrinsic sharp-pointed SERS spectrum can be obtained in target substance.Therefore, can provide a kind of and improve transducer sensitivity and according to the sensor chip of SERS spectrum intended target material.In addition, by suitably changing the height of cycle of the first convex form and height, the second convex form, thus any wavelength of the location matches of resonance peak can be made.Therefore, suitably can select the wavelength of the light irradiated when intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described first convex form periodically arranges along the first direction parallel with described planar portions, and periodically arranges along second direction that is parallel with described planar portions, that intersect with described first direction.Like this, with only periodically form the situation of the first convex form along the direction (first direction) parallel with the planar portions of matrix material compared with, sensing detection can be carried out under wider resonant condition.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material.Further, except the cycle that can suitably change on the first direction of the first convex form, the cycle in second direction can also suitably be changed.Therefore, the wavelength of the light irradiated when suitably can change intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described second convex form periodically arranges along the third direction parallel with described planar portions.Like this, the cycle of the second convex form can suitably be changed.Therefore, suitably can select the wavelength of the light irradiated when intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described second convex form periodically arranges along fourth direction that is parallel with described planar portions, that intersect with described third direction.Like this, with only periodically form the situation of the second convex form along the direction (third direction) parallel with the planar portions of matrix material compared with, sensing detection can be carried out under wider resonant condition.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material.Further, except the cycle that can suitably change on the third direction of the second convex form, the cycle in fourth direction can also suitably be changed.Therefore, the wavelength of the light irradiated when suitably can change intended target material, and can measurement range be expanded.
In sensor chip of the present invention, preferred multiple described second convex form is made up of particulate.Like this, can provide a kind of and improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material.
In sensor chip of the present invention, preferably when the width of the first convex form on described first direction is set to W1, when distance between adjacent two described first convex forms on described first direction is set to W2, meet the relation of W1 > W2.Like this, owing to exciting the space filling factor of first convex form of LSPR to increase, therefore with meet W1 < W2 relation situation compared with, sensing detection can be carried out under wider plasma resonance condition.And, the energy irradiating light when determining target substance can be effectively utilized.
In sensor chip of the present invention, the ratio of the described distance W2 between adjacent two described first convex forms on the described width W 1 of described first convex form on preferred described first direction and described first direction meets the relation of W1:W2=9:1.Like this, sensing detection can be carried out under wider plasma resonance condition.And, the energy irradiating light when determining target substance can be effectively utilized.
In sensor chip of the present invention, the metal preferably forming the described surface of described diffraction grating is gold or silver-colored.Like this, because gold or silver have the characteristic showing SPP, LSPR, SERS, therefore can show SPP, LSPR, SERS easily, thus target substance can be detected in high sensitivity.
The sensor box of a fifth aspect of the present invention comprises: the sensor chip of above-mentioned record; Delivery section, for being transported to described target substance on the surface of described sensor chip; Mounting portion, for loading described sensor chip; Housing, for accommodating described sensor chip, described delivery section and described mounting portion; And illumination window, be arranged on the position relative with the surface of described sensor chip of described housing.
According to a fifth aspect of the invention, because have the sensor chip of above-mentioned record, so optionally light splitting Raman diffused light, and target molecule can be detected.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor box of SERS spectrum intended target material.
The analytical equipment of a sixth aspect of the present invention comprises: the sensor chip of above-mentioned record; Light source, for irradiating light to described sensor chip; And photodetector, for detecting the light obtained by described sensor chip.
According to a sixth aspect of the invention, because have the sensor chip of above-mentioned record, so optionally light splitting Raman diffused light, and target molecule can be detected.Therefore, can provide a kind of and improve transducer sensitivity and can according to the analytical equipment of SERS spectrum intended target material.
Accompanying drawing explanation
Figure 1A and Figure 1B is the mode chart of the schematic configuration of the sensor chip that the embodiment that the present invention relates to is shown.
Fig. 2 A and Fig. 2 B is the schematic diagram of Raman scattering optical spectroscopy.
Fig. 3 A and Fig. 3 B is the schematic diagram of the mechanism of the electric-field enhancing utilizing LSPR.
Fig. 4 is the schematic diagram of SERS optical spectroscopy.
Fig. 5 is the coordinate diagram of the intensity of reflected light that the first projection monomer is shown.
Fig. 6 is the coordinate diagram of the dispersion plot that SPP is shown.
Fig. 7 is the coordinate diagram of the intensity of reflected light that the first projection monomer is shown.
Fig. 8 A and Fig. 8 B is the coordinate diagram of the intensity of reflected light that the first projection monomer is shown.
Fig. 9 A and Fig. 9 B is the coordinate diagram of the intensity of reflected light that the first projection monomer is shown.
Figure 10 is the coordinate diagram of the intensity of reflected light of the sensor chip that the embodiment that the present invention relates to is shown.
Figure 11 A ~ Figure 11 C is the coordinate diagram of the intensity of reflected light of the structure that overlapping second projection in the planar portions of matrix part is shown.
Figure 12 is the mode chart of the sensor chip defining multiple second projection in the planar portions of matrix part.
Figure 13 is the schematic diagram of the intensity of reflected light of sensor chip in Figure 12.
Figure 14 A ~ Figure 14 F is the schematic diagram of the production process of sensor chip.
Figure 15 is the summary construction diagram of the variation that the sensor chip with the first projection is shown.
Figure 16 A and Figure 16 B is the summary construction diagram of the variation of the sensor chip with the second projection.
Figure 17 A and Figure 17 B is the summary construction diagram of the variation of the sensor chip with the second projection.
Figure 18 is the mode chart of an example of analytical equipment.
Figure 19 is the mode chart of the schematic configuration of the sensor chip that the embodiment that the present invention relates to is shown.
Figure 20 is the mode chart of the schematic configuration of the sensor chip that the embodiment that the present invention relates to is shown.
Embodiment
Below, with reference to accompanying drawing, embodiments of the present invention are described simultaneously.Such embodiment only illustrates one embodiment of the present invention, does not limit the present invention, can random variation within the scope of technological thought of the present invention.And in accompanying drawing below, for ease of understanding each structure, the reduced scale of each structure and number etc. are different from the structure of reality.
Figure 1A and Figure 1B is the mode chart of the schematic configuration of the sensor chip that the embodiment that the present invention relates to is shown.Figure 1A is the stereographic map of the schematic configuration of sensor chip, and Figure 1B is the sectional view of the schematic configuration of sensor chip.In fig. ib, label P1 represents the cycle of the first projection (the first convex form), label P2 represents the cycle of the second projection (the second convex form), label W1 represents the width of the first projection, label W2 represents the distance between two adjacent the first projections, label T1 represents the height (groove depth) of the first projection, and label T2 represents the height (groove depth) of the second projection.
Figure 19 and Figure 20 is corresponding to Figure 1B, the mode chart of the schematic configuration of the sensor chip of an embodiment that the present invention relates to.In Figure 19 and Figure 20, label P1 represents the cycle of the first projection (the first convex form), label P2 represents the cycle of the second projection (the second convex form), label W1 represents the width of the first projection, label W2 represents the distance between two adjacent the first projections, label T1 represents the height (groove depth) of the first projection, and label T2 represents the height (groove depth) of the second projection.
In order to the diffraction grating 9 formed on the metallic matrix part 10 of bag configures target substance, and utilize surface plasmon resonance (LSPR:Localized Surface Plasmon Resonance) and Surface enhanced raman spectroscopy (SERS:Surface Enhanced Raman Scattering) to detect above-mentioned target substance, and use sensor chip 1.
In order to be formed at matrix part 10 diffraction grating 9 on configure target substance, and utilize LSPR and SERS detect above-mentioned target substance and use sensor chip 1.Diffraction grating 9 comprises: multiple first projection 11, along the first direction parallel with the planar portions of matrix part 10, is less than or equal to the cycle P1 of 1000nm to arrange multiple first projection 11 to be more than or equal to 100nm; Multiple base part 10a, between adjacent two the first projections 11, forms the substrate of matrix part 10; And multiple second projection 12, be formed on the respective 11a above of multiple first projection 11.Diffraction grating 9 has the surface formed by metal, and it is formed on the planar portions 10s of matrix part 10.
In other words, diffraction grating 9 has the first concaveconvex shape, the second concaveconvex shape, overlap and the composite mode (composite pattern) that obtains, and diffraction grating 9 has the surface formed by metal.In above-mentioned first concaveconvex shape, along the direction vertical with the planar portions 10s of matrix part 10, the cycle P1 being less than or equal to 1000nm to be more than or equal to 100nm is arranged with multiple first convex form (the first projection) 11, in above-mentioned second concaveconvex shape, on each first convex form 11 in multiple first convex form 11, be periodically arranged with multiple second convex form (the second projection) 12 by the cycle P2 shorter than the cycle of the first concaveconvex shape.
Further, so-called " diffraction grating " refers to the structure that multiple concaveconvex shape (multiple projection) is periodically arranged here.
In addition, so-called " planar portions " refers to the upper surface portion of matrix part here.That is, so-called " planar portions " refers to the one-sided surface element of the matrix part being configured with target substance.Further, overlapping by the first concaveconvex shape, the second concaveconvex shape and composite mode that is that formed at least is formed in the upper surface portion of matrix part.And, for the lower face of another one-sided surface element of matrix part, i.e. matrix part, be not particularly limited its shape.But if consider to carry out manufacturing procedure etc. to the planar portions (upper surface portion) of matrix part, then the lower face of preferred substrate parts is faces parallel and smooth relative to the base part of planar portions.
As shown in Figure 1B, can exemplify matrix part 10, first convex form 11 and the second convex form 12 is all the structure that is made up of the metal structure as diffraction grating 9.In addition, as shown in figure 19, exemplify following structure: form matrix part 10 and the first convex form 11 with the insulating element such as glass or resin, the overall position of exposing with metal film covering insulating element, and on metal film, form the second convex form 12 be made up of metal.In addition, as shown in figure 20, exemplify following structure: matrix part 10, first convex form 11 and the second convex form 12 are all formed by insulating element, and cover the insulating element overall position of exposing by metal film.That is, diffraction grating 9 has following structure: the base part 10a of matrix part 10, the first convex form 11 and the second convex form 12 at least surface comprises metal are formed.
Matrix part 10 has the structure of the metal film such as forming more than 150nm on the glass substrate.By production process described later, this metal film becomes the first projection 11 and the second projection 12.Moreover, although use the matrix being formed with metal film on the glass substrate as matrix part 10 in the present embodiment, be not limited in this.Such as, also can be used in quartz base plate or sapphire substrate are formed with metal film matrix as matrix part 10.In addition, the flat board be made up of metal can also be used as matrix part.
First projection 11 is formed as the height T1 on the planar portions 10s of matrix part 10 with regulation.This first projection 11 arranges with the cycle P1 shorter than the wavelength of light on the direction (first direction) parallel with the planar portions 10s of matrix part 10.At cycle P1, the width W 1 of the first projection 11 monomer on first direction (left and right directions of Figure 1B) is added (P1=W1+W2) with the distance W2 between adjacent two the first projections 11.In addition, the first projection 11 is convex forms of square-section, and multiple first projection 11 is formed as overlooking line and space (line and space) (striated).
In the first projection 11, preferably such as cycle P1 is set within the scope of 100nm ~ 1000nm, height T1 is set within the scope of 10nm ~ 100nm.Like this, just the first projection 11 can be played a role as the structure showing LSPR.
The width W 1 of the first projection 11 on this first direction is greater than the distance W2 (W1 > W2) between two adjacent the first projections 11.Thus, the space filling factor of the first projection 11 that LSPR excites increases.
The upper surface 11a that multiple first projection 11 is respective is formed with plural second projection 12 in the mode with specified altitude T2.Specifically, the second projection 12 is not formed on the base part 10a (the planar portions 10s of the matrix part 10 in the region between adjacent two the first projections 11) of matrix part 10, is only formed on the upper surface 11a of the first convex form 11.
This second projection 12 arranges with the cycle P2 shorter than the wavelength of light on the direction (third direction) parallel with the planar portions 10s of matrix part 10.At cycle P2, the distance between the width of the second projection 12 monomer on third direction (left and right directions of Figure 1B) and adjacent two the second projections 12 is added.Therefore, the cycle P2 of the second projection 12 wants much shorter than the cycle P1 of the first projection 11.
In the second projection 12, preferably such as cycle P2 is set smaller than the value of 500nm, height T2 is set smaller than the value of 200nm.Like this, just the second projection 12 can be played a role as the structure showing SERS.
In addition, in the present embodiment, the orientation (first direction) of the first projection 11 is identical with the orientation (third direction) of the second projection 12.And the same with the first projection, the second projection 12 forms the convex form of square-section, multiple second projection 12 is formed overlooks line and space (striated).
As the surface metal of diffraction grating 9, such as gold (Au), silver (Ag), copper (Cu), aluminium (Al) or their alloy can be used.In the present embodiment, gold or the silver with the characteristic showing SPP, LSPR, SERS is used.Thus, be easy to show SPP, LSPR, SERS, and target substance can be detected in high sensitivity.
At this, be described with regard to SPP, LSPR, SERS.If light is injected the surface of sensor chip 1, is namely formed with the face of multiple first projection 11 and multiple second projection 12, then can utilize the surperficial eigentone (surface plasma) of multiple first projection 11.But the polarized condition of incident light is TM (Transverse Magnetic, the transverse magnetic wave) polarized light vertical with the groove direction of the first projection 11.So along with the vibration of free electron, electromagnetic vibration is excited.Because of the vibration of this electromagnetic vibration effect free electron, so system, the i.e. so-called surface plasma excimer (SPP:Surface Plasmon Polariton) of both vibration combinations can be generated.In addition, although in the present embodiment light to inject angle substantially vertical relative to chip surface, if be in the condition exciting SPP, then inject angle and be not limited in this angle (vertically).
This SPP along sensor chip 1 surface, transmit along the interface of air and the second projection 12 specifically, near the second projection 12, excite strong internal field.The coupling of SPP is to the wavelength sensitive of light, and this coupling efficiency is higher.Like this, according to the incident light being in air transmission pattern, surface plasmon resonance (LSPR:Localized Surface PlasmonResonance) can be excited by SPP.Further, Surface enhanced raman spectroscopy (SERS:Surface Enhanced Raman Scattering) can be utilized according to the relation between LSPR and Raman diffused light.
Fig. 2 A and Fig. 2 B is the schematic diagram of Raman scattering optical spectroscopy.Fig. 2 A shows Raman scattering light splitting ratio juris.Fig. 2 B illustrates Raman spectrum (relation of Raman shift and Raman scattering intensities).In fig. 2, label L represents incident light (light of single wavelength), and label Ram represents Raman diffused light, and label Ray represents Rayleigh scattering light, and label X represents target molecule (target substance).In fig. 2b, transverse axis represents Raman shift.In addition, so-called Raman shift refers to the difference of the vibration number of Raman diffused light Ram and the vibration number of incident light L, gets distinctive value in the structure of target molecule X.
As shown in Figure 2 A, if the light L of single wavelength irradiates target molecule X, then in scattered light, there is the light (Raman diffused light Ram) that wavelength is different from the wavelength of incident light.Energy difference between Raman diffused light Ram and incident light L correspond to the vibrational energy level of target molecule X and rotational energy level, or the energy of electron level.Target molecule X because having the distinctive vibrational energy corresponding with its structure, so by using the light L of single wavelength to carry out intended target molecule X.
Such as, when the vibrational energy of incident light L is set as V1, be set as V2 with the vibrational energy that target molecule X consumes, when the vibrational energy of Raman diffused light Ram is set as V3, V3=V1-V2.In addition, though most of incident light L also have after colliding with target molecule X with collision before identical energy.This elastic scattering light is called as Rayleigh scattering light Ray.Such as, when the vibrational energy of Rayleigh scattering light Ray is set as V4, then V4=V1.
According to Raman spectrum as shown in Figure 2 B, if the scattering strength of the scattering strength of Raman diffused light Ram (spectrum peak) with Rayleigh scattering light Ray is compared, then known Raman diffused light Ram is the low light level.Like this, Raman scattering optical spectroscopy is following assay method: although remarkable to the recognition capability of target molecule X, be very low to the sensitivity of target molecule X sensing detection itself.Therefore, in the present embodiment, with optical spectroscopy (SERS optical spectroscopy) to realize high sensitivity, this optical spectroscopy employs Surface enhanced raman spectroscopy (with reference to Fig. 4).
Fig. 3 A and Fig. 3 B is the schematic diagram of the mechanism of the electric-field enhancing utilizing LSPR.Fig. 3 A is mode chart light being incided the metallic nanoparticle period of the day from 11 p.m. to 1 a.m.Fig. 3 B is the schematic diagram that LSPR strengthens electric field.In figure 3 a, label 100 represents light source, and label 101 represents metal nanoparticle, and label 102 represents the light from light source injection.In figure 3b, label 103 presentation surface internal field.
As shown in Figure 3A, if the incident metal nanoparticle 101 of light 102, then along with the vibration of light 102, free electron resonates.In addition, metal nanoparticle diameter is less than the wavelength of incident light.Such as, the wavelength of light is 400nm ~ 800nm, metal nanoparticle diameter is 10 ~ 100nm.In addition, use Ag, Au as metal nanoparticle.
So, along with the resonance of free electron, near metal nanoparticle 101, excite strong surperficial internal field 103 (with reference to figure 3B).Like this, by incident for light 102 metal nanoparticle 101, thus LSPR can be excited.
Fig. 4 is the schematic diagram of SERS optical spectroscopy.In the diagram, label 200 represents substrate (being equivalent to the first projection of the embodiment that the present invention relates to), label 201 represents metal Nano structure (being equivalent to the second projection of the embodiment that the present invention relates to), label 202 represents selective adsorption film, label 203 represents enhancing electric field, and label 204 represents target molecule, and label 211 represents incident laser, label 212 represents Raman diffused light, and label 213 represents Rayleigh scattering light.In addition, selective adsorption film 202 adsorbed target molecule 204.
As shown in Figure 4, if the incident metal Nano structure 201 of laser 211, then along with the vibration of laser 211, free electron resonates.The size of metal Nano structure 201 is less than the wavelength of incident laser.So, along with the resonance of free electron, near metal Nano structure 201, excite strong surperficial internal field.Thus, LSPR is excited.Further, if the distance between adjacent metal Nano structure 201 diminishes, then near its contact, there is extremely strong enhancing electric field 203.If adsorb one to several target molecule 204 on its contact, then can there is SERS in there.About this point, the result of the enhancing electric field generated between closely connect two Nano silver grains that also can calculate according to using finite time-domain difference (FDTD:Finite Difference Time Domain) method confirms.Therefore, optionally light splitting is carried out to Raman diffused light, and target molecule can be detected in high sensitivity.
As mentioned above, present embodiment has following structure: by the first projection 11 along the direction parallel with the planar portions of matrix part 10, by the cycle P1 shorter than the wavelength of light arrangement excite LSPR.Further, present embodiment also has following structure: show SERS by 11a on the first projection 11 being formed plural second projection 12.Specifically, based on by the illumination of single wavelength being mapped to the principle that target molecule can occur in Raman scattering, target molecule is distributed between two adjacent the second projections 12, and makes to produce near this contact to strengthen magnetic field, thus produce SERS.Thus, SERS optical spectroscopy can be used to detect target substance in mode highly sensitive compared with Raman scattering optical spectroscopy.
Fig. 5 is the coordinate diagram of the intensity of reflected light that the first projection monomer is shown.In Figure 5, transverse axis represents the wavelength of light, and the longitudinal axis represents the intensity of reflected light.Using the height T1 of the first projection 11 as parameter (T1=20nm, 30nm, 40nm).And, in the structure of the sensor chip 1 of present embodiment, deduct the difference after intensity of reflected light as absorbance using from incident intensity (being set as 1.0).
Light vertical incidence first projection 11.Polarisation of light light direction is TM polarized light.The cycle of the first projection 11 is 580nm, and the resonance peak (peak) of intensity of reflected light is present near wavelength 630nm.This resonance peak is from SPP, if the height T1 of the first projection 11 is increased, then resonance peak is to long wavelength side (long wavelength region) displacement.When the height T1 of the first projection 11 is 30nm, known intensity of reflected light becomes the strongest, absorbs and also shows the strongest.
Fig. 6 is the coordinate diagram of the dispersion plot that SPP is shown.In figure 6, label C1 represents the dispersion plot (such as, the value at the boundary surface place of air and Au being shown) of SPP, and label C2 represents light (light line).The cycle of the first projection 11 is 580nm.Transverse axis shows the position (2 π/P corresponding on the transverse axis of Fig. 6) of the grating vector of the first projection 11.If from this position upwards extended line, then crossing with the dispersion plot of SPP.Wavelength corresponding to this intersection point can be obtained by following formula.
In formula (1), P1 represents the cycle of the first projection 11, and E1 represents the complex permittivity of air, and E2 represents the complex permittivity of Au.If P1, E1, E2 are substituted in formula (1), then obtain λ=620nm (ω 0 corresponding on the longitudinal axis of Fig. 6).
The height T1 of the first projection 11 become large while, the imaginary part of the wave number of SPP becomes large.Thus, the real part of the wave number of SPP diminishes, and the intersection point of the line extended from the position of grating vector and the dispersion plot of SPP moves to left down from upper right.That is, resonance peak is to long wavelength side displacement.
Fig. 7 is the coordinate diagram of the intensity of reflected light that the first projection monomer is shown.In the figure 7, transverse axis represents the wavelength of light, and the longitudinal axis represents intensity of reflected light.Using the ratio (hereinafter referred to " dutycycle ") of the distance W2 between the width W 1 of the first projection 11 on first direction and adjacent two the first projections as parameter (W1:W2=5:5,8:2).In addition, the coordinate diagram of the parameter W1:W2=5:5 of this figure is identical with the coordinate diagram of the parameter T1=30 of Fig. 5.
TM polarized light vertical incidence first projection 11.When the cycle of the first projection 11 are 580nm, dutycycle be W1:W2=5:5 time, the resonance peak of intensity of reflected light is present near wavelength 630nm.In addition, when dutycycle is W1:W2=8:2, the resonance peak of intensity of reflected light is present near wavelength 660nm.If dutycycle increases, then the gradient of resonance peak is sharpened, and resonance peak is to long wavelength side displacement.
Fig. 8 A ~ Fig. 9 B is the coordinate diagram of the intensity of reflected light that the first projection monomer is shown.The coordinate diagram that Fig. 8 A is dutycycle when being W1:W2=7:3.The coordinate diagram that Fig. 8 B is dutycycle when being W1:W2=3:7.The coordinate diagram that Fig. 9 A is dutycycle when being W1:W2=9:1.The coordinate diagram that Fig. 9 B is dutycycle when being W1:W2=1:9.In Fig. 8 A ~ Fig. 9 B, transverse axis represents the wavelength of light, and the longitudinal axis represents intensity of reflected light.Using the height T1 of the first projection 11 as parameter (T1=20nm, 30nm, 40nm, 50nm).
TM polarized light vertical incidence first projection 11.When the dutycycle of the first projection 11 is W1:W2=7:3, when height T1 is 30nm, the resonance peak of intensity of reflected light is present near wavelength 660nm (with reference to figure 8A).On the other hand, when dutycycle is W1:W2=3:7, when height T1 is 40nm, the resonance peak of intensity of reflected light is present near wavelength 600nm (with reference to figure 8B).When the known dutycycle when the first projection 11 is W1:W2=7:3, if height T1 increases, then the resonant positions of intensity of reflected light is to long wavelength side displacement.But when the known dutycycle when the first projection 11 is W1:W2=3:7, the resonant positions of intensity of reflected light is almost constant.
When the dutycycle of the first projection 11 is W1:W2=9:1, and when height T1 is 40nm, the resonance peak of intensity of reflected light is present near wavelength 670nm (with reference to figure 9A).On the other hand, when dutycycle is W1:W2=1:9, when height T1 is 20nm, the resonance peak of intensity of reflected light is present near wavelength 730nm, the gradient mild (with reference to figure 9B) of resonance peak.When the known dutycycle when the first projection 11 is W1:W2=9:1, if height T1 increases, then the resonant positions of intensity of reflected light is to long wavelength side displacement.But when the dutycycle of the first projection 11 is W1:W2=1:9, the resonance peak of intensity of reflected light is very little.
Figure 10 is the structure that overlapping second projection 12 in the first projection 11 is shown, a kind of coordinate diagram of intensity of reflected light of sensor chip 1 of embodiment that namely the present invention relates to.In Fig. 10, transverse axis represents the wavelength of light, and the longitudinal axis represents intensity of reflected light.Using the height T2 of the second projection 12 as parameter (T2=0nm, 30nm).In addition, the coordinate diagram when coordinate diagram during parameter T2=0 of this figure and parameter W1:W2=8:2 in Fig. 7 is identical.
TM polarized light vertical incidence first projection 11.The dutycycle of the first projection 11 is W1:W2=8:2, and the height T1 of the first projection 11 is 30nm.In addition, the cycle P2 of the second projection 12 is 116nm.By only forming multiple second projection 12 on the upper surface 11a of the first projection 11, thus the position of the resonance peak of intensity of reflected light moves near wavelength 710nm from wavelength 660nm.Further, sharpness and the gradient of resonance peak can be ensured.This resonance peak is from above-mentioned SERS.When the height T2 of the second projection 12 is 30nm, by irradiating with the light of wavelength 710nm, thus strong internal field can be excited to the near surface of second raised 12.In addition, by suitably change the first projection 11 and the second projection 12 cycle P1, P2 and height T1, T2, resonant positions can be made to mate any wavelength.
Figure 11 A ~ Figure 11 C is the coordinate diagram of the intensity of reflected light of the structure that overlapping second projection 12 on matrix part 10 is shown.Figure 11 A coordinate diagram of (omitting diagram) when to be that the planar portions (base part of matrix part) of the matrix part in region respectively between the upper surface and adjacent two the first projections of the first projection is upper form multiple second projection.Figure 11 B is the coordinate diagram of only when the upper surface of the first projection forms multiple second projection (structure of the sensor chip of the embodiment that the present invention relates to).Figure 11 C coordinate diagram of (omitting diagram) when to be that the planar portions (base part of matrix part) of the matrix part in region only between adjacent two the first projections is upper form multiple second projection.In Figure 11 A ~ Figure 11 C, transverse axis represents the wavelength of light, and the longitudinal axis represents intensity of reflected light.Using the height T2 of the second projection 12 as parameter (T2=0nm, 40nm).In addition, the coordinate diagram during parameter T2=0 of this figure is identical with the coordinate diagram in Fig. 5 during parameter T1=30.
TM polarized light vertical incidence first projection 11.The cycle of the first projection 11 is 580nm, and dutycycle is W1:W2=5:5, and height T1 is 30nm.In addition, the cycle P2 of the second projection 12 is 97nm, and height T2 is 40nm.
Known by forming multiple second projection respectively on the upper surface of the first projection and the base part of matrix part, thus the resonant positions of intensity of reflected light moves to (with reference to figure 11A) near wavelength 730nm from wavelength 640nm.Further, known by only forming multiple second projection 12 on the upper surface 11a of the first projection 11, thus the resonant positions of intensity of reflected light moves to (with reference to figure 11B) near wavelength 710nm from wavelength 640nm.Even if but also knownly only forming multiple second projection in the base part of matrix part, then the resonant positions of intensity of reflected light is still almost constant.
Mainly propagated along the interface between air and the upper surface of the first projection by the known SPP of these results.Therefore, only the first projection upper surface and do not form plural second projection as exciting LSPR and the structure making SERS manifest further is effectively in the base part of matrix part.In addition, due to the dutycycle (W1 > W2) by increase first projection, excite the space filling factor of first projection of LSPR to increase, therefore, when can effectively utilize intended target material, irradiate the energy of light.
Figure 12 is when only forming the second projection 12 and do not form the first projection 11 on the planar portions 10s of matrix part 10 on the planar portions 10s of matrix part 10, the schematic diagram of sensor chip 2 when defining multiple second projection 12 on the planar portions 10s of matrix part 10.
Figure 13 is the coordinate diagram of the intensity of reflected light of the sensor chip 2 illustrated when to form multiple second projection on the planar portions 10s of matrix part 10.In fig. 13, transverse axis represents the wavelength of light, and the longitudinal axis represents intensity of reflected light.Using the height T2 of the second projection 12 as parameter (T2=0nm, 40nm, 80nm).TM polarized light vertical incidence second projection 12.Also the resonance peak of intensity of reflected light cannot be confirmed from this figure.Result is known thus, time when there is not the first projection 11, not by SPP, and cannot couples optical energy in the second projection 12.
Figure 14 A ~ Figure 14 F is the schematic diagram of the production process of sensor chip.First, on glass substrate 30, Au film 31 is formed by the method such as vapour deposition method or sputtering method.Then, Au film 31 applies resist layer 32 (with reference to figure 14A) by methods such as spin-coating methods (spin coat method).At this moment, the thickness Ta of Au film 31 is formed as the thick degree (such as 200nm) to not saturating incident light.。
Then, utilize the methods such as stamped method (imprint method), form the corrosion-resisting pattern 32a (with reference to figure 14B) that cycle Pa is 580nm.Next, using this corrosion-resisting pattern 32a as mask, by dry ecthing method, Au film 31 is only etched the degree of depth D1 (such as 70nm) of regulation.Then, by removing corrosion-resisting pattern 32a, thus the first projection 31a (with reference to figure 14C) is formed.
Then, the Au film 31 being formed with the first projection 31a applies resist layer 33 (with reference to figure 14D) by methods such as spin-coating methods.Then, utilize the methods such as stamped method only to be formed on the upper surface of the first projection 31a corrosion-resisting pattern 33a (with reference to figure 14E) that cycle Pb is 116nm.Subsequently, using this corrosion-resisting pattern 33a as mask, by dry ecthing method only to the degree of depth D2 (such as 40nm) of the first projection 31a etching regulation.Afterwards, corrosion-resisting pattern 33a is removed, form the second projection 31b (with reference to figure 14F).By above operation, the sensor chip 3 of the embodiment that the present invention relates to can be made.
Sensor chip 1 according to an embodiment of the present invention, by the metal superfine structure based on the first projection 11, excites LSPR by SPP, and can show SERS further by the metal superfine structure based on the second projection 12.Specifically, if light incidence is formed with the face of multiple first projection 11 and multiple second projection 12, then the surperficial eigentone (surface plasma) because multiple first projection 11 causes can be there is.So along with the vibration of light, free electron produces resonance, and SPP is excited, and excites strong surperficial internal field near multiple second projection 12.Like this, LSPR is excited.In this configuration, because the distance between adjacent two the second projections 12 is little, so extremely strong enhancing electric field can be produced near its contact.Further, if adsorbed one to several target substance on this contact, SERS will have been produced.Therefore, the narrowed width of intensity of reflected light spectrum, resonance peak obtains sharp-pointed strength characteristics, and transducer sensitivity can be made to improve.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor chip 1 of SERS spectrum determination target substance.In addition, by suitably changing the height T2 of the cycle P1 of the first projection 11 and height T1, the second projection 12, thus any wavelength of the location matches of resonance peak can be made.Like this, suitably can select the wavelength of the light irradiated when intended target material, and expand measurement range.
In addition, according to this structure, because periodically configure the second projection 12, so the cycle P2 of the second projection 12 suitably can be changed along the third direction parallel with the planar portions of matrix part 10.Like this, suitably can select the wavelength of the light irradiated when intended target material, and expand measurement range.
Further, according to this structure, owing to using gold or silver as the surface metal of diffraction grating 9, therefore, can be easy to manifest LSPR, SERS, and target substance can be detected in high sensitivity.
In addition, according to this structure, dutycycle due to the first projection 11 meets the relation of W1 > W2, the space filling factor of the first projection 11 that LSPR is excited increases, so with meet W1 < W2 relation situation compared with, sensing detection can be carried out under wider plasma resonance condition.And, the energy of the light irradiated when can effectively utilize intended target material.
In addition, even if when the dutycycle of the first projection 11 meets the relation of W1:W2=9:1, also can carry out sensing detection under very wide plasma resonance condition, the energy irradiating light can be effectively utilized simultaneously.
In addition, although show in the present embodiment along the direction (first direction) parallel with the planar portions of matrix part 10, arrange the first projection 11 structure by the cycle P1 shorter than the wavelength of light, be not limited in this.Figure 15 is used to be described the sensor chip with the structure different from the first projection 11 of present embodiment.
Figure 15 has the stereographic map with the schematic configuration of the sensor chip 4 of the first projection 41 of above-mentioned first projection 11 different modes.In addition, in detail in this figure, conveniently, the diagram of the second projection is eliminated.
As shown in figure 15, the first projection 41 is formed on the planar portions 40s of substrate 40.This first projection 41 is arranged by the cycle P3 shorter than the wavelength of light along the direction (first direction) parallel with the planar portions of substrate 40.In addition, along the second direction perpendicular to first direction parallel with the planar portions of substrate 40, the first projection 41 is arranged by the cycle P4 shorter than the wavelength of light.In addition, second direction is not limited in the direction perpendicular to first direction parallel with the planar portions of substrate 40, also can be the direction that intersect at first direction parallel with the planar portions of substrate 40.
According to this structure, with only periodically form the situation of the first projection along the direction (first direction) parallel with the planar portions of matrix part 10 compared with, sensing detection can be carried out under wider resonant condition.Therefore, can provide a kind of and improve transducer sensitivity and can according to the sensor chip 4 of SERS spectrum intended target material.Further, except suitably can changing the cycle P3 of the first direction of the first projection, the cycle P4 of second direction can also suitably be changed.Therefore, the wavelength of the light irradiated when suitably can change intended target material, and can measurement range be expanded.
And, although show along the direction (third direction) parallel with the planar portions of matrix part 10 in the present embodiment, by the cycle P2 shorter than the wavelength of light arrange the second projection 12 structure, namely to show the orientation (first direction) of the first projection 11 and the orientation (third direction) of the second projection 12 are unidirectional structures, but be not limited in this.The sensor chip 5,6,7,8 with the second projection 12 different structure of Figure 16 A ~ Figure 17 B couple and present embodiment is used to be described.
Figure 16 A and Figure 16 B has the stereographic map with the Sketch of the sensor chip of the second projection of above-mentioned second projection 12 different modes.Figure 16 A shows sensor chip 5, Figure 16 B with the second projection 52 and shows the sensor chip 6 with the second projection 62.
As shown in Figure 16 A, the upper surface 51a that multiple first projections 51 only on the planar portions 50s being formed at matrix part 50 are respective forms plural second projection 52.That is, the second projection 52 is not formed on the base part 50a of matrix part 50.In detail in this figure, as an example, the intersecting angle showing the orientation (first direction) of the first projection 51 and the orientation (third direction) of the second projection 52 is the structure of 45 degree.
As shown in fig 16b, the upper surface 61a that multiple first projections 61 only on the planar portions 60s being formed at matrix part 60 are respective forms plural second projection 62.That is, the second projection 62 is not formed on the base part 60a of matrix part 60.In detail in this figure, as an example, the intersecting angle showing the orientation (first direction) of the first projection 61 and the orientation (third direction) of the second projection 62 is the structure of 90 degree.
Even if also can provide a kind of in such a configuration to improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material under wider plasma resonance condition.
Figure 17 A and Figure 17 B be have with the sensor chip of the second projection of above-mentioned second projection 12 different modes overlook enlarged drawing.Figure 17 A shows sensor chip 7, Figure 17 B with the second projection 72 and shows the sensor chip 8 with the second projection 82.
As shown in Figure 17 A, only on the upper surface 71a that multiple first projection (not shown) is respective, plural second projection 72 is formed with.In addition, the second projection 72 is periodically arranged along parallel with the planar portions of substrate fourth direction of intersecting with third direction.In detail in this figure, as an example, show the second projection 72 in overlooking circular structure.In addition, the second projection 72 also can not in periodically configuration but random arrangement.
As seen in this fig. 17b, only on the upper surface 81a that multiple first projection (not shown) is respective, plural second projection 82 is formed with.In addition, the second projection 82 is periodically arranged along parallel with the planar portions of substrate fourth direction of intersecting with third direction.In detail in this figure, as an example, show the second projection 82 in overlooking oval structure.In addition, the second projection 82 also can not in periodically configuration but random arrangement.
According to this structure, compared with being only formed in the situation on the direction (third direction) parallel with the planar portions of matrix part with the second projection, sensing detection can be carried out under wider plasma resonance condition.Therefore, can provide a kind of and improve transducer sensitivity and according to the sensor chip of SERS spectrum intended target material.In addition, except suitably can changing the cycle of the third direction of the second projection, the cycle of fourth direction can also suitably be changed.Therefore, the wavelength of the light irradiated when suitably can change intended target material, and can measurement range be expanded.
In addition, although form the second projection by the Au film be formed on the upper surface of glass substrate is formed pattern in the present embodiment, this is not limited in.Such as, the second projection also can be particulate.Even if also can provide a kind of in such a configuration to improve transducer sensitivity and can according to the sensor chip of SERS spectrum intended target material.
In addition, although in the present embodiment, same metal (gold or silver) is used as the metal comprised in the metal comprised in the metal comprised in matrix part, the first projection, the second projection, to be not limited in this.Such as, the metal gold that also can will comprise in matrix part, the metal silver comprised in first projection, the alloy of the metal comprised in the second projection gold and silver such, different metal (gold, silver, copper, aluminium or their alloy) combine rear use.
(analytical equipment)
Figure 18 is the mode chart of an example of the analytical equipment of the sensor chip being equipped with the embodiment that the present invention relates to.In addition, the arrow in Figure 18 represents the throughput direction of target substance (omitting diagram).
As shown in figure 18, analytical equipment 1000 comprise sensor chip 1001, light source 1002, photodetector 1003, collimation lens 1004, polarized light control element 1005, dichronic mirror 1006, to thing lens 1007, to thing lens 1008, delivery section 1010.Light source 1002 and photodetector 1003 are electrically connected with control device (illustrating slightly) respectively by distribution.
Light source 1002 generates the laser for exciting LSPR and SERS.The laser penetrated from light source 1002 becomes directional light by collimation lens 1004, by polarized light control element 1005, is guided by the direction of dichronic mirror 1006 to sensor chip 1001, by converging thing lens 1007, thus incident sensor chip 1001.At this moment, the surface (such as, being formed with the face of metal Nano structure and the selection mechanism of detection thing) of sensor chip 1001 is configured with target substance (diagram slightly).In addition, target substance is imported into delivery section 1010 inside by controlling the driving of fan (diagram slightly) from input port 1011, thus it is outside to be discharged to delivery section 1010 from escape hole 1012.And the size of metal Nano structure is less than the wavelength of laser.
When the incident metal Nano structure of laser, along with the vibration of laser, free electron resonates, and near metal Nano structure, excite strong internal field, thus, LSPR is excited.Further, if the distance between adjacent metal Nano structure diminishes, then near its contact, produce extremely strong enhancing electric field, if adsorb one to several target substance on its contact, then SERS can occur.
The light (Raman diffused light and Rayleigh scattering light) utilizing sensor chip 1001 to obtain, by thing lens 1007, is guided by the direction of dichronic mirror 1006 to photodetector 1003, by converging thing lens 1008, thus incident light detecting device 1003.In addition, carry out spectral resolution by photodetector 1003, thus can spectral information be obtained.
According to this structure, owing to possessing the sensor chip of the embodiment that the invention described above relates to, so optionally light splitting Raman diffused light, and detect target molecule.Therefore, can provide a kind of and improve transducer sensitivity and according to the analytical equipment 1000 of SERS spectrum intended target material.
Analytical equipment 1000 comprises sensor box 1100.Sensor box 1100 comprise sensor chip 1001, for target substance is transported to the surface of sensor chip 1001 delivery section 1010, for load sensor chip 1001 mounting unit 1101, for accommodating the housing 1110 of above-mentioned parts.The position relative with sensor chip 1001 of housing 1110 is provided with illumination window 1111.The laser irradiated from light source 1002, by illumination window 1111, is irradiated to the surface of sensor chip 1001.Sensor box 1100 is positioned at the top of analytical equipment 1000, and it is set to load and unload relative to the body of analytical equipment 1000.
According to this structure, owing to possessing the sensor chip of the embodiment that the invention described above relates to, so optionally light splitting Raman diffused light, and target molecule can be detected.Therefore, can provide a kind of and improve transducer sensitivity and according to the sensor box 1100 of SERS spectrum intended target material.
The analytical equipment of the embodiment that the present invention relates to can be widely used in the sensing device of arcotic and explosive detection, medical treatment and Gernral Check-up, food inspection.And, can be used as the use such as affinity type sensor (affinity sensor) detected with or without species adsorbs, as in antigen-antibody reaction with or without Antigen adsorption etc.
Claims (20)
1. an analytical equipment, is characterized in that, comprising:
Sensor chip;
Light source, generates laser;
Collimation lens, becomes described laser into directional light;
Polarized light control element, makes described directional light pass through;
Photodetector, detects the light obtained by described sensor chip;
To thing lens, converge the scattered light in described sensor chip; And
Dichronic mirror, by the photoconduction by described polarized light control element to described sensor chip, by described to thing lens for the scattered light guiding in described sensor chip,
Wherein, described sensor chip comprises: glass basis parts, have planar portions; And diffraction grating, the surface of described diffraction grating is metal, and is formed in described planar portions, and described diffraction grating comprises: multiple first projection, along the first direction parallel with described planar portions, arrange with being less than or equal to the cycle of 1000nm by being more than or equal to 100nm; Base part, is made up of the planar portions of the described glass basis parts in the region between the first adjacent projection; And multiple second projection, be formed in the upper surface of multiple described first projection, form the structure overlapping with described first projection.
2. analytical equipment according to claim 1, is characterized in that,
Multiple described first projection periodically arranges along second direction that is parallel with described planar portions, that intersect with described first direction.
3. analytical equipment according to claim 1, is characterized in that,
Multiple described second projection periodically arranges along the third direction parallel with described planar portions.
4. analytical equipment according to claim 3, is characterized in that,
Multiple described second projection periodically arranges along fourth direction that is parallel with described planar portions, that intersect with described third direction.
5. analytical equipment according to claim 1, is characterized in that,
Multiple described second projection is made up of particulate.
6. analytical equipment according to claim 1, is characterized in that,
When the width of the first projection on described first direction is set to W1, when the distance between adjacent two described first projections on described first direction is set to W2, meet the relation of W1 > W2.
7. analytical equipment according to claim 6, is characterized in that,
The ratio of the described distance W2 between adjacent two described first projections on the described width W 1 of described first projection on described first direction and described first direction meets the relation of W1:W2=9:1.
8. analytical equipment according to claim 1, is characterized in that,
Described analytical equipment comprises sensor box,
Described sensor box comprises:
Delivery section, can be transported to target substance the surface of described sensor chip;
Mounting portion, can load described sensor chip;
Housing, can accommodate described sensor chip, described delivery section and described mounting portion; And
Illumination window, is arranged on the position relative with the surface of described sensor chip of described housing.
9. a manufacture method for the described sensor chip in analytical equipment according to claim 1, is characterized in that, comprising:
The step of described metal is formed on the surface of glass substrate;
The step of corrosion-resisting pattern is formed at described metallic surface;
Described corrosion-resisting pattern is etched described metal as mask, forms the step of the first projection;
The step of corrosion-resisting pattern is formed at the upper surface of described first projection; And
Described corrosion-resisting pattern is etched described metal as mask, forms the step of the second projection.
10. the manufacture method of sensor chip according to claim 9, is characterized in that,
The described metal formed in the step of the described metal of formation is formed as thickness at more than 150nm.
11. 1 kinds of analytical equipments, is characterized in that, comprising:
Sensor chip;
Light source, generates laser;
Collimation lens, becomes described laser into directional light;
Polarized light control element, makes described directional light pass through;
Photodetector, detects the light obtained by described sensor chip;
To thing lens, converge the scattered light in described sensor chip; And
Dichronic mirror, by the photoconduction by described polarized light control element to described sensor chip, by described to thing lens for the scattered light guiding in described sensor chip,
Wherein, described sensor chip comprises: glass basis parts, have planar portions, and diffraction grating, the surface of described diffraction grating is metal, and be formed in described planar portions, described diffraction grating comprises: have the synthesising pattern by the first concaveconvex shape and the second concaveconvex shape overlap being formed in described planar portions, wherein, in described first concaveconvex shape, along the first direction parallel with described planar portions, multiple first convex form is arranged with being less than or equal to the cycle of 1000nm by being more than or equal to 100nm, in described second concaveconvex shape, multiple second convex form is arranged on multiple described first convex form by the cycle shorter than the cycle of described first concaveconvex shape.
12. analytical equipments according to claim 11, is characterized in that,
Multiple described first convex form periodically arranges along the first direction parallel with described planar portions, and periodically arranges along second direction that is parallel with described planar portions, that intersect with described first direction.
13. analytical equipments according to claim 11, is characterized in that,
Multiple described second convex form periodically arranges along the third direction parallel with described planar portions.
14. analytical equipments according to claim 13, is characterized in that,
Multiple described second convex form periodically arranges along fourth direction that is parallel with described planar portions, that intersect with described third direction.
15. analytical equipments according to claim 11, is characterized in that,
Multiple described second convex form is made up of particulate.
16. analytical equipments according to claim 11, is characterized in that,
When the width of the first convex form on described first direction is set to W1, when the distance between adjacent two described first convex forms on described first direction is set to W2, meet the relation of W1 > W2.
17. analytical equipments according to claim 16, is characterized in that,
The ratio of the described distance W2 between adjacent two described first convex forms on the described width W 1 of described first convex form on described first direction and described first direction meets the relation of W1:W2=9:1.
18. analytical equipments according to claim 11, is characterized in that,
Described analytical equipment comprises sensor box,
Described sensor box comprises:
Delivery section, can be transported to target substance the surface of described sensor chip;
Mounting portion, can load described sensor chip;
Housing, can accommodate described sensor chip, described delivery section and described mounting portion; And
Illumination window, is arranged on the position relative with the surface of described sensor chip of described housing.
The manufacture method of the described sensor chip in 19. 1 kinds of analytical equipments according to claim 11, is characterized in that, comprising:
The step of described metal is formed on the surface of glass substrate;
The step of corrosion-resisting pattern is formed at described metallic surface;
Described corrosion-resisting pattern is etched described metal as mask, forms the step of the first convex form;
The step of corrosion-resisting pattern is formed at the upper surface of described first convex form; And
Described corrosion-resisting pattern is etched described metal as mask, forms the step of the second convex form.
The manufacture method of 20. sensor chips according to claim 19, is characterized in that,
The described metal formed in the step of the described metal of formation is formed as thickness at more than 150nm.
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009-263706 | 2009-11-19 | ||
| JP2009263706 | 2009-11-19 | ||
| JP2009281480 | 2009-12-11 | ||
| JP2009-281480 | 2009-12-11 | ||
| JP2010-192838 | 2010-08-30 | ||
| JP2010-192839 | 2010-08-30 | ||
| JP2010192839A JP5655435B2 (en) | 2009-11-19 | 2010-08-30 | Sensor chip, sensor cartridge and analyzer |
| JP2010192838A JP5565215B2 (en) | 2009-12-11 | 2010-08-30 | Sensor chip, sensor cartridge and analyzer |
| CN2010105510695A CN102072879B (en) | 2009-11-19 | 2010-11-18 | Sensor chip, sensor cartridge, and analysis apparatus |
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| CN2010105510695A Division CN102072879B (en) | 2009-11-19 | 2010-11-18 | Sensor chip, sensor cartridge, and analysis apparatus |
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| CN103018211A CN103018211A (en) | 2013-04-03 |
| CN103018211B true CN103018211B (en) | 2015-07-01 |
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| RU2017120043A (en) * | 2016-06-20 | 2018-12-07 | Форд Глобал Текнолоджиз, Ллк | METHOD AND SYSTEM FOR DETECTION OF SOLID PARTICLES IN EXHAUST GASES |
| CN108645836A (en) * | 2018-04-28 | 2018-10-12 | 中山大学 | Stacked in parallel double-level-metal optical grating construction surface enhanced Raman substrate and preparation method thereof |
| CN108593627A (en) * | 2018-06-03 | 2018-09-28 | 深圳拓扑精膜科技有限公司 | A kind of Raman spectrum base, manufacturing process and application |
| TWI802187B (en) * | 2021-12-28 | 2023-05-11 | 國立臺灣大學 | Detection platform and method for detecting abused drugs |
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| WO2007108556A1 (en) * | 2006-03-20 | 2007-09-27 | Canon Kabushiki Kaisha | Detecting device, detecting unit substrate, detecting unit, target substance detecting kit and detecting method |
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| CN103018210A (en) | 2013-04-03 |
| TW201140034A (en) | 2011-11-16 |
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| TW201140033A (en) | 2011-11-16 |
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