JPWO2014007134A1 - Sensor chip - Google Patents

Abstract

[PROBLEMS] To simplify the apparatus by omitting the polarizing plate arranged between the light source and the dielectric, reduce the number of parts, and the range of selection of usable dielectric and adhesive materials Thus, a sensor chip capable of maintaining good adhesion between a dielectric and a metal thin film is provided. [Solution] In detecting an analyte trapped by a ligand on a metal thin film 24, a sensor used in an optical specimen detection apparatus that detects the analyte by irradiating the metal thin film 24 with excitation light. A sensor chip that is a chip 22, wherein a polarizing member 25 is disposed on a dielectric member 23, and a metal thin film 24 is disposed on the polarizing member 25.

Description

  The present invention relates to a sensor chip, and more specifically, a surface plasmon resonance (SPR) measuring device, or surface plasmon-field enhanced fluorescence spectroscopy (SPFS) using a surface plasmon resonance phenomenon (SPFS). The present invention relates to a sensor chip used for an optical specimen detection device such as a surface plasmon excitation enhanced fluorescence measurement device based on the principle of the above.

  2. Description of the Related Art Conventionally, when detecting a very small substance, various specimen detection apparatuses that can detect such a substance by applying a physical phenomenon of the substance have been used.

  As one of such specimen detection devices, the phenomenon of obtaining high light output (surface plasmon resonance (SPR) phenomenon) by resonating electrons and light in a minute region such as nanometer level. For example, a surface plasmon resonance device (hereinafter referred to as “SPR device”) that detects minute analytes in a living body can be used.

  In addition, based on the principle of surface plasmon excitation enhanced fluorescence spectroscopy (SPFS) using the surface plasmon resonance (SPR) phenomenon, it is possible to perform analyte detection with higher accuracy than the SPR device. The surface plasmon excitation enhanced fluorescence measurement device (hereinafter referred to as “SPFS device”) is also one of such specimen detection devices.

  In this surface plasmon excitation enhanced fluorescence spectroscopy (SPFS), surface plasmon light is applied to the surface of the metal thin film under the condition that excitation light such as laser light irradiated from the light source is attenuated by total reflection (ATR) on the surface of the metal thin film. By generating (dense wave), the photon amount of excitation light irradiated from the light source is increased to several tens to several hundred times, and the electric field enhancement effect of surface plasmon light is obtained.

  By the way, as a sensor chip used in such an SPR device or SPFS device, a glass chip is conventionally used as a dielectric member, and a metal thin film is formed on the glass prism by vapor deposition. .

  However, since glass prisms as well as metal thin films are expensive, it is not practical to replace sensor chips using glass prisms, for example, every time an analyte is measured.

  Thus, in recent years, sensor chips using resin prisms instead of glass prisms have been provided.

  FIG. 6 shows an SPR device 30 using a conventional sensor chip disclosed in Patent Document 1.

  In the sensor chip 10 of the surface plasmon resonance device (SPR device 30), a resin prism 11 is employed as a dielectric member for allowing light to enter, and the resin prism 11 is a transparent resin such as PMMA (polymethyl methacrylate resin). It is formed by. The metal thin film 12 is formed on the upper surface of the resin prism 11. Further, the sample 13 to be inspected is disposed on the metal thin film 12.

In such an SPR device 30, the incident light L emitted from the light source 1 enters from one surface 11 b of the resin prism 11 on which the metal thin film 12 is not provided, and the resin prism 11 and the metal thin film 12 is reflected at the interface 11a, the reflected light emitted from the other surface 11c of the resin prism 11, the light L ₁ having a desired wavelength selected by the wavelength selection unit 20, the light L which is selected by the wavelength selecting unit 20 The light intensity distribution of ₁ is picked up by a CCD (Charge Coupled Device) image sensor 3 as a two-dimensional image.

  As described above, in the SPR device 30 using surface plasmon resonance, the polarizing plate 9 is disposed between the light source 1 and the resin prism 11, and light incident on the resin prism 11 by the polarizing plate 9 is converted into P-polarized light. It is limited to light that has been waved.

  By the way, in such an SPR device 30, in order to adjust the incident angle of the incident light L incident on the metal thin film 12 from the light source 1 via the resin prism 11 and to examine the resonance angle, the light source 1 is made to be a resin prism. It is necessary to move in a circular arc shape around 11.

  In that case, it is necessary to move the polarizing plate 9 together with the light source 1 in an arc shape.

  However, when the polarizing plate 9 is moved in an arc shape in this way, there is a problem that the structure of the apparatus becomes complicated.

  In addition, the conventional SPR device 30 shown in FIG. 6 requires a polarizing plate 9 for P-polarization in the vicinity of the light source 1 in addition to the sensor chip 10, so that the number of parts increases accordingly. was there.

  On the other hand, in the SPFS device 90 shown in FIG. 7 to which such a surface plasmon resonance (SPR) phenomenon is applied, the sensor chip 10 substantially similar to the SPR device 30 is used. That is, the sensor chip 10 of the SPFS device 90 employs a resin prism 11 as a dielectric member, and a metal thin film 12 is formed on the upper surface of the resin prism 11 by vapor deposition.

In the SPFS device 90, a light source 1 that irradiates incident light L toward the metal thin film 12, a polarizing plate 9, and a light receiving means 78 that receives reflected light L ₂ irradiated from the light source 1 and reflected by the metal thin film 12 are provided. ing.

  Further, on the side opposite to the light source 1 with respect to the metal thin film 12, there is provided a light detection means 84 for receiving the fluorescence 82 emitted from the fluorescent substance labeled with the analyte.

  In addition, between the metal thin film 12 and the light detection means 84, the condensing member 86 for efficiently collecting the fluorescence 82, and the wavelength that removes light other than the fluorescence 82 and passes only the necessary fluorescence 82. A selection function member 88 is provided.

  In the SPFS device 90, first, a ligand is fixed on the metal thin film 12, and an analyte labeled with a fluorescent substance is captured by the ligand.

In this state, incident light L is irradiated from the light source 1 into the resin prism 11, and the incident light L is incident on the metal thin film 12 at the resonance angle θ ₂ , so that a dense wave (surface plasmon) is formed on the metal thin film 12. ).

When a dense wave (surface plasmon) is generated on the metal thin film 12, the incident light L excited and the electronic vibration in the metal thin film 12 are coupled to reduce the light amount of the reflected light L _2. If a point where the signal of the reflected light L ₂ received by the means 78 changes (the amount of light decreases) is found, the resonance angle θ _{2 at} which a dense wave (surface plasmon) occurs can be obtained.

  Due to the phenomenon of generating this density wave (surface plasmon), the fluorescent substance of the analyte trapped by the ligand on the metal thin film 12 is efficiently excited, thereby increasing the amount of fluorescence 82 emitted from the fluorescent substance.

  The increased fluorescence 82 is received by the light detection means 84 through the light collecting member 86 and the wavelength selection function member 88, whereby the analyte can be detected.

  By the way, the autofluorescence of the resin prism 11 is stronger than the autofluorescence of the glass prism. As a result, in the SPFS device 90, the autofluorescence of the resin prism 11 is mixed with the fluorescence 82 of the sample 13 to be inspected, and the autofluorescence becomes noise of the fluorescence 82 and is detected by the light detection means 84. There was a problem.

  Therefore, in such an SPFS device 90, there is a limitation on selection of a resin material that can be used as the resin prism 11, for example.

  Further, in the SPFS device 90, when the metal thin film 12 is fixed to the upper surface of the resin prism 11 using an adhesive, the influence of autofluorescence of the adhesive cannot be ignored. As a result, the selection of the adhesive material for fixing the resin prism 11 is also limited.

JP 2007-192841 A

  In view of such a situation, the present invention provides a polarizing plate that is disposed between a light source and a dielectric member so as to P-polarize incident light in an optical specimen detection device such as an SPR device or an SPFS device. It is an object of the present invention to provide a sensor chip that can simplify the apparatus by reducing the number of components and can reduce the number of components.

  Furthermore, in the present invention, in an optical specimen detection apparatus such as an SPFS apparatus, a part of the autofluorescence generated by the dielectric member or the like can be shielded to suppress the autofluorescence received by the light detection means, and the material of the dielectric member The object is to provide a sensor chip capable of improving the degree of freedom of selection.

In order to achieve at least one of the above objects, a sensor chip reflecting one aspect of the present invention is:
In detecting an analyte trapped by a ligand on a metal thin film, a sensor chip used in an optical specimen detection apparatus that detects the analyte by irradiating the metal thin film with excitation light. ,
A polarizing member is disposed on the dielectric member, and a metal thin film is disposed on the polarizing member.

  Here, the “polarizing member” refers to a member that transmits only P-polarized light in the incident light. Specifically, a linear polarizing plate, a liquid crystal film, a liquid crystal panel, etc. can be illustrated, and what is necessary is just a translucent member containing a linear polarizing plate.

  According to the present invention, it is also possible to use an adhesive containing a material that could not be used due to autofluorescence. Therefore, in the SPFS apparatus, the selection range of the dielectric member and the adhesive material can be expanded. Further, the polarizing plate disposed between the light source and the dielectric member can be omitted. This eliminates the need for the polarizing plate in the vicinity of the light source and eliminates the need for a device for moving the polarizing plate in an arc shape, thereby simplifying the device and reducing the number of components.

  Further, in the SPFS device, a part of the autofluorescence generated by the dielectric member or the like can be suppressed by the polarizing member and received by the light detection means, and can be used for strong autofluorescence so far. The dielectric member can be formed from a resin or the like of the material that could not be formed. Similarly, it is also possible to use an adhesive that could not be used due to autofluorescence.

  Therefore, in the SPFS apparatus, the selection range of the dielectric member and the adhesive material can be expanded.

FIG. 1 is a schematic diagram of an SPR device employing a sensor chip according to an embodiment of the present invention. FIG. 2 is a schematic view around the sensor chip shown in FIG. FIG. 3 is a schematic view of a sensor structure in which a flow path forming member is disposed above a sensor chip according to an embodiment of the present invention instead of a well member. FIG. 4 is a schematic view of an SPFS device employing a sensor chip according to an embodiment of the present invention. FIG. 5 is a graph showing the positional relationship between the excitation light and the mask when a liquid crystal film is used as a support for supporting the metal thin film. FIG. 6 is a side view of the SPR device disclosed in Patent Document 1 in which a conventional sensor chip is employed. FIG. 7 is a side view of an SPFS device employing a conventional sensor chip.

  Hereinafter, embodiments of the present invention will be described in more detail with reference to the drawings.

  FIG. 1 is a schematic view of an SPR device 70 employing a sensor chip according to an embodiment of the present invention, and FIG. 2 is a schematic view around the sensor chip in FIG.

  In this embodiment, the metal thin film 24 is formed on the polarizing member 25, and the polarizing member 25 functions as a support for the metal thin film 24.

  As shown in FIG. 2, the sensor member 18 is configured by the metal thin film 24 and the polarizing member 25.

  In addition, the sensor chip 18 is configured by bonding such a sensor member 18 to the upper surface of the dielectric member 23 with the adhesive 21.

The dielectric member 23 is not particularly limited, but optically transparent materials such as various inorganic materials such as glass and ceramics, natural polymers, and synthetic polymers can be used. From the viewpoints of performance, production stability, and optical transparency, those containing silicon dioxide (SiO ₂ ) or titanium dioxide (TiO ₂ ) are preferred.

  In this embodiment, the prism-shaped dielectric member 23 having a substantially trapezoidal vertical cross-sectional shape is employed. However, the vertical cross-sectional shape is triangular (so-called triangular prism), semicircular shape, semi-elliptical shape, etc. The shape of the dielectric member 23 can be changed as appropriate.

  If a dielectric prism made of resin such as natural polymer or synthetic polymer is used as the dielectric member 23 (hereinafter also referred to as resin prism when the dielectric member 23 is a resin dielectric prism), a glass prism is used. Compared to, it can be formed at a low cost. Therefore, the resin prism is excellent in practicality.

  Further, as the dielectric member 23, for example, a flat light guide plate can be adopted. However, when a light guide plate is employed as the dielectric member 23, it is necessary to adjust the incident angle for total reflection of incident light, and therefore it is necessary to make light incident from the end face on the edge side.

  The polarizing member 25 may be a film like a liquid crystal film or a plate like a liquid crystal panel.

  Thus, if the polarizing member 25 is comprised from the liquid-crystal member, the irradiation range of light can be controlled easily.

  Moreover, the polarizing member 25 is not limited to a liquid crystal member, and what is necessary is just a translucent member including a linearly polarizing plate.

  The material of the metal thin film 24 is not particularly limited, but is preferably made of at least one metal selected from the group consisting of gold, silver, aluminum, copper, and platinum, and more preferably made of gold. Further, it may be made of an alloy containing any one of these metals.

  Such a metal or alloy is suitable as the metal thin film 24 because it is stable against oxidation and the electric field enhancement due to dense waves (surface plasmons) increases.

  The method for forming the metal thin film 24 is not particularly limited, and examples thereof include a sputtering method, a vapor deposition method (resistance heating vapor deposition method, electron beam vapor deposition method, etc.), an electrolytic plating method, an electroless plating method, and the like. It is done. Of these, the sputtering method and the vapor deposition method are preferable because the thin film formation conditions can be easily adjusted.

  Further, the thickness of the metal thin film 24 is in the range of gold: 5 to 500 nm, silver: 5 to 500 nm, aluminum: 5 to 500 nm, copper: 5 to 500 nm, platinum: 5 to 500 nm, and alloys thereof: 5 to 500 nm. It is preferable to be within. From the viewpoint of the electric field enhancement effect, within the range of gold: 20-70 nm, silver: 20-70 nm, aluminum: 10-50 nm, copper: 20-70 nm, platinum: 20-70 nm, and alloys thereof: 10-70 nm More preferably.

  If the thickness of the metal thin film 24 is within the above range, a sparse / dense wave (surface plasmon) is likely to be generated. Further, the size (length × width) of the metal thin film 24 is not particularly limited.

  Further, since it is difficult to directly provide a ligand on the metal thin film 24, first, a solid phase film made of SAM (Self-Assembled Monolayer) is provided on the upper layer of the metal thin film 24, or CMD is provided on the SAM. It is preferable to provide a solid phase film provided with (carboxymethyl dextran) and provide a ligand on the solid phase film.

  Thus, if a solid phase film is provided to provide the ligand, a sufficient separation distance between the analyte captured by the ligand and the metal thin film 24 can be secured, so that the fluorescence metal quenching can be suppressed. Can be prevented. Therefore, the detectability of the fluorescent substance attached to the analyte can be improved, and the sensor sensitivity can be improved.

  In this embodiment, the sensor chip 22 is incorporated as a part of the sensor assembly 26 so that the sensor chip 22 formed as described above can be easily handled.

  That is, the sensor assembly 26 includes a pair of plate-like holding members 26a and 26b, a seal member 31, and fastening means 36 such as a screw integrally connecting the pair of plate-like holding members 26a and 26b. It is configured.

  By providing the seal member 31 between the sensor chip 22 and the plate-like holding member 26b, it is possible to ensure the sealing performance when the sample solution 38 is filled in the plate-like holding member 26b.

  Further, since the pair of plate-like holding members 26a and 26b are integrally connected by the fastening means 36 such as a screw, the water tightness of the sample solution 38 in the liquid reservoir 40 is sufficiently secured. .

  Of the pair of plate-shaped sandwiching members 26 a and 26 b disposed above and below the sensor chip 22, one sandwiching member 26 a disposed on the lower side in FIG. 1 has the same shape as the outer surface of the dielectric member 23. The base member side of the dielectric member 23 is accommodated in a mortar-shaped through hole surrounded by the slope 41, thereby preventing the movement of the dielectric member 23. Has been.

  Further, the other clamping member 26b disposed on the upper side of FIG. 1 in the dielectric member 23 functions as a well member that can temporarily store the sample solution 38 containing the analyte in the living body, for example. ing.

  Further, in this embodiment, the dielectric member 23 and the polarizing member 25 are bonded with the adhesive 21, but instead of the adhesive 21, a refractive index matching liquid can be filled therein.

  As the refractive index matching liquid, a conventionally known refractive index matching liquid (matching oil) can be used. For example, by filling an ultraviolet curable adhesive, an adhesive fixing function can be exhibited in addition to refractive index matching. be able to.

  In the SPR device 70 of the present embodiment, the light source 33 and the light receiving means 34 are disposed below the sensor assembly 26, and the light source 33 and the light receiving means 34 have a position adjustment for adjusting the irradiation position and the light receiving position. Means 42, 43 are provided.

  The excitation light 44 emitted from the light source 33 is preferably laser light, and an LD laser having a wavelength of 200 to 900 nm and 0.001 to 1,000 mW, or a semiconductor laser having a wavelength of 230 to 800 nm and 0.01 to 100 mW is suitable. .

  In order to detect, for example, an in-vivo analyte using the SPR device configured as described above, first, a sample solution 38 containing a fluorescent substance that labels the analyte to be detected is stored in a liquid reservoir. 40 is supplied. By maintaining this state, the analyte labeled with the fluorescent substance is captured by the ligand on the metal thin film 24.

  In addition, after supplying the analyte containing the analyte into the liquid reservoir 40, a solution containing a fluorescent substance for labeling the analyte may be supplied into the liquid reservoir 40.

  Examples of the specimen containing such an analyte include blood, serum, plasma, urine, nasal fluid, saliva, stool, body cavity fluid (spinal fluid, ascites, pleural effusion, etc.).

  The analyte contained in the sample is, for example, a nucleic acid (DNA that may be single-stranded or double-stranded, RNA, polynucleotide, oligonucleotide, PNA (peptide nucleic acid), etc., or nucleoside , Nucleotides and their modified molecules), proteins (polypeptides, oligopeptides, etc.), amino acids (including modified amino acids), carbohydrates (oligosaccharides, polysaccharides, sugar chains, etc.), lipids, or their modified molecules, composites Specific examples include carcinoembryonic antigens such as AFP (α-fetoprotein), tumor markers, signal transmitters, hormones, and the like, and are not particularly limited.

  Further, in this state, the light source 33 irradiates the metal thin film 24 with the excitation light 44, and the excitation light 44 enters the metal thin film 24 at a specific incident angle θa, so that a dense wave (surface plasmon) is generated on the metal thin film 24. Will come to occur.

  When a dense wave (surface plasmon) is generated on the metal thin film 24, the excitation light 44 and the electronic vibration in the metal thin film 24 are coupled, and the amount of reflected light 50 is reduced. If a point where the light quantity of the reflected light 50 received by the means 34 decreases is found, a resonance angle at which a dense wave (surface plasmon) is generated can be obtained.

  Since the resonance angle changes depending on the presence or absence of the analyte, if the resonance angle when the sample solution not containing the analyte is supplied to the liquid reservoir 40 is checked in advance, the resonance angle varies depending on the resonance angle. It can be known whether or not the analyte is contained in the sample solution 38.

  Hereinafter, the operation of the SPR device 70 having the above configuration in which the sensor chip 22 according to the present invention is employed will be described.

  That is, in this embodiment, since the polarizing member 25 is installed on the dielectric member 23, the excitation light 44 can be P-polarized by using this polarizing member 25.

  Therefore, in the SPR device 70 of the present embodiment, it is not necessary to install the polarizing plate 9 at the position shown in FIG.

  Thereby, the number of parts can be reduced and the apparatus can be downsized.

  As mentioned above, although one Example of this invention was described, this invention is not limited to the said Example at all.

  For example, in the above embodiment, the other clamping member 26b that immovably clamps the sensor chip 22 functions as a well member and the sample solution 38 is stored, but the inspection is performed. The sample solution 38 can be circulated with respect to the inspection position, or the sample solution 38 can be moved back and forth with respect to the inspection position.

  For example, FIG. 3 shows a sensor structure 54 (for example, including the sensor structure 54) in which a flow path forming member 52 capable of moving the sample solution 38 with respect to the inspection position is disposed above the sensor chip 22. It can also be called a sensor chip as a whole.) In the case of such a sensor structure 54 using the flow path forming member 52, the sample solution 38 stored in the liquid reservoir 40 can be reciprocated through the flow path forming member 52 or circulated in one direction. it can.

  Furthermore, in the said Example, although the sensor chip 22 used for the SPR apparatus 70 was demonstrated, such a sensor chip is applicable also to a SPFS apparatus.

  FIG. 4 is a schematic diagram of an SPFS device 80 in which the sensor chip 60 is employed.

  In the SPFS device 80 of the present embodiment, the same components as those in the SPR device 70 shown in FIG.

  In the sensor chip 60 shown in FIG. 4, a liquid crystal film 56 is employed as a polarizing member. Also, a resin prism 58 is employed as the dielectric member. The metal thin film 24 is provided on the upper surface of the liquid crystal film 56, and the liquid crystal film 56 is bonded to the resin prism 58 by the adhesive 21.

  That is, the sensor chip 60 of the present embodiment is composed of the resin prism 58, the adhesive 21, the liquid crystal film 56, and the metal thin film 24.

  The liquid crystal film 56 functioning as a polarizing member is connected to a control device 51 for turning on / off voltage application for each dot.

  In the SPFS device 80, only the light collecting member 35 for efficiently collecting light and the fluorescent light 32 are selectively transmitted above the sensor chip 60 (specifically, the main fluorescent light to be detected). A wavelength selection function member 28 formed so as to selectively transmit light in a predetermined wavelength range including a wavelength) and a light detection means 29 are provided.

  The photodetection means 29 is not particularly limited, but for example, an ultrasensitive photomultiplier tube, a CCD (Charge Coupled Device) image sensor capable of multipoint measurement, a CMOS (Complementary Metal Oxide Semiconductor) image sensor, or the like is used. Can do.

  In such an SPFS device 80, the excitation light 44 is irradiated from the light source 33 and is incident on the side surface of the resin prism 58 from below the resin prism 58. At this time, the excitation light 44 is irradiated through the resin prism 58 toward the metal thin film 24 formed on the upper surface of the resin prism 58 at an incident angle θa.

  On the other hand, the light intensity of the fluorescence 32 is measured by the light detection means 29.

  Further, the fluorescence 32 is received by the light detection means 29 while changing the incident angle of the excitation light 44 to the metal thin film 24, and the light intensity of the fluorescence 32 is measured.

  The relationship between the incident angle θa of the excitation light 44 and the light intensity of the fluorescence 32 can be measured, and the ATR condition (total reflection attenuation condition) can be measured.

  That is, when the excitation light 44 is irradiated onto the metal thin film 24 of the sensor chip 60, surface plasmon light (dense wave) is generated on the metal thin film 24, and the fluorescence 32 is proportional to the intensity of the surface plasmon light (dense wave). Therefore, the ATR condition can be measured by finding the incident angle at which the light intensity of the fluorescence 32 received by the light detection means 29 changes (for example, the light quantity increases most). It becomes possible.

  As the condensing member 35, any condensing system may be used as long as it aims at efficiently condensing the fluorescent signal on the light detecting means 29. As a simple condensing system, for example, a commercially available objective lens used in a microscope or the like may be used. The magnification of the objective lens is preferably 10 to 100 times.

  As the wavelength selection function member 28, an optical filter, a cut filter, or the like can be used.

  Examples of the optical filter include a neutral density (ND) filter and a diaphragm lens. In addition, the cut filter includes external light (illumination light outside the apparatus), excitation light (excitation light transmission component), stray light (excitation light scattering component at various points), and plasmon scattering light (excitation light 44 originated). Scattered light generated by the influence of structures or deposits on the surface of the sensor chip 60), and a filter for removing various noise light such as autofluorescence of the oxygen fluorescent substrate, such as an interference filter, a color filter, etc. Can be mentioned.

  When such an SPFS device 80 is used, the excitation light 44 is incident on the metal thin film 24 at an incident angle (resonance angle) that satisfies the ATR condition, whereby high intensity surface plasmon light (on the metal thin film 24 ( (Dense wave) will occur.

  The surface plasmon light (dense wave) efficiently excites the fluorescent material on the metal thin film 24, thereby increasing the amount of the fluorescent light 32 emitted from the fluorescent material. By receiving light by the light detection means 29 via 28, it is possible to detect a minute amount and / or extremely low concentration of the analyte.

  In the SPFS device 80 of this embodiment, even when the resin prism 58 or the adhesive 21 for fixing the liquid crystal film 56 is applied to the upper surface of the resin prism 58, autofluorescence emitted from these members is emitted. Can be reduced by the liquid crystal film 56. Therefore, according to the present invention, when the sensor chip 60 is configured, the range of selection of materials for the resin prism 58 and the adhesive 21 can be expanded.

  Therefore, it is possible to form the resin prism 58 using the special polyester for optics, which has the advantage that the refractive index is high until now but cannot be used due to strong autofluorescence. Therefore, it is possible to obtain a higher electric field strength higher than that of the resin prism 58 used so far.

  Further, in the SPFS device 80 according to one embodiment of the present invention, since the liquid crystal film 56 is used as the polarizing member, the irradiation area of the excitation light 44 that irradiates the metal thin film 24 can be electrically controlled. That is, since it becomes possible to turn on and off each dot of the liquid crystal film 56, a mechanical mask can be dispensed with. Thereby, the apparatus can be made compact.

  Furthermore, by using the liquid crystal film 56, as shown in FIG. 5, the boundary between the portion irradiated with the excitation light and the portion not irradiated with the excitation light by the mask becomes clear, so that the liquid pool shown in FIG. Light that has passed through the part 40 other than the measurement area (irradiation area) is not received by the light detection means 29. Therefore, an accurate light amount can be measured by the light detection means 29.

  As described above, the configuration of the SPFS device 80 using the sensor chip 60 has been described. However, in such an SPFS device 80, the metal thin film 24 constituting the sensor chip 60 is installed on the liquid crystal film 56. P-polarization can be performed by the liquid crystal film 56.

  Even if a material that cannot ignore autofluorescence is used as the resin prism 58 or the adhesive 21, the autofluorescence can be reduced by the liquid crystal film 56. Therefore, it is possible to suppress detection of autofluorescence of the resin prism 58 and the adhesive 21 as noise of the fluorescence 32.

  Thereby, the range of selection of the material of the resin prism 58 as the dielectric member and the adhesive 21 for fixing can be expanded.

  Therefore, it is possible to use, for example, an optical special polyester as a material for the resin prism 58, which has been advantageous so far, although it has an advantage of a high refractive index, and has not been able to be used due to strong autofluorescence.

  Further, in the sensor chip 60 employed in the SPFS device 80, the liquid crystal film 56 is used as the polarizing member. However, for example, a polarizing film, a polarizing plate, or the like may be employed. Of course, when the liquid crystal film 56 is not used as the polarizing member, the control device 51 shown in FIG. 4 is unnecessary.

  Further, in the sensor chip 60 employed in the SPFS device 80 of the present embodiment, the liquid crystal film 56 is bonded to the resin prism 58 by the adhesive 21, but the use of the adhesive 21 is not essential. For example, when a polarizing plate is adopted as the polarizing member, the polarizing plate may be sandwiched between the resin prisms 58 by the fastening means 36 such as screws without using the adhesive 21. In such a case, it is preferable to fill a refractive index matching liquid between the polarizing plate and the resin prism 58.

  If the sensor chip 60 is not bonded between the polarizing plate and the resin prism 58 as described above, the sensor member 18 composed of the metal thin film 24 and the polarizing member 25 is used as shown in FIG. Can be freely separated from the resin prism 58. Thereby, the resin prism 58 can be repeatedly used as it is.

  Further, the present invention is not limited to the case where the upper surface shape of the metal thin film 24 is a planar shape, and it is needless to say that the present invention can be applied to a case where the metal thin film 24 is formed in an uneven surface shape formed in a lattice shape.

DESCRIPTION OF SYMBOLS 1 Light source 9 Polarizing plate 10 Sensor chip 11 Resin prism 12 Metal thin film 18 Sensor member 21 Adhesive 22 Sensor chip 23 Dielectric member 24 Metal thin film 25 Polarizing member 26 Sensor assembly 26b The other clamping member (well member)
28 Wavelength selection function member 29 Light detection means 31 Sealing member 32 Fluorescence 33 Light source 34 Light receiving means 35 Condensing member 36 Fastening means 38 Sample solution 39 Through hole 40 Liquid reservoirs 42 and 43 Position adjustment means 44 Excitation light 50 Reflected light 51 Control Device 52 Flow path forming member 54 Sensor structure 56 Liquid crystal film 58 Resin prism 60 Sensor chip 70 SPR device 80 SPFS device

Claims (9)

In detecting an analyte trapped by a ligand on a metal thin film, a sensor chip used in an optical specimen detection apparatus that detects the analyte by irradiating the metal thin film with excitation light. ,
A sensor chip, wherein a polarizing member is disposed on a dielectric member, and a metal thin film is disposed on the polarizing member.   The sensor chip according to claim 1, wherein the polarizing member is a liquid crystal member.   The ligand is installed on the metal thin film via a solid phase film made of SAM (Self-Assembled Monolayer) or a solid film made of CMD (carboxymethyl dextran) on the SAM. Item 3. The sensor chip according to Item 1 or 2.   The sensor chip according to claim 1, wherein the dielectric member is a dielectric prism.   On the upper surface side of the dielectric member, a well member for temporarily storing the sample solution containing the analyte, or a flow path forming member capable of circulating the sample solution containing the analyte is provided. The sensor chip according to any one of claims 1 to 4.   The sensor chip according to claim 5, wherein a seal member is interposed between the well member or the flow path forming member and the dielectric member.   The sensor chip according to claim 5, wherein a refractive index matching liquid is filled between the dielectric member and the polarizing member.   The sensor member according to claim 5, wherein the well member or the flow path forming member and the dielectric member are detachably fixed by fastening means.   The sensor chip according to claim 1, wherein the dielectric member is made of resin.

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