JP5825342B2 - Support structure and measuring device - Google Patents

Description

  The present invention relates to a measurement device that performs measurement by surface plasmon excitation fluorescence spectroscopy and a support structure in the measurement device.

  When excitation light traveling in the dielectric medium is reflected on the interface between the metal film and the dielectric medium, an evanescent wave leaks from the interface, and plasmons on the surface of the metal film interfere with the evanescent wave. When the incident angle of the excitation light to the interface is set to the resonance angle and the plasmon and the evanescent wave resonate, the electric field of the evanescent wave is remarkably enhanced.

  In surface plasmon excited fluorescence spectroscopy (SPFS), this enhanced electric field is utilized. That is, the antigen is captured on the surface of the metal film, the captured antigen is fluorescently labeled, and an enhanced electric field is allowed to act on the fluorescent label. When the enhanced electric field acts on the fluorescent label, fluorescence is emitted from the fluorescent label, and the amount of fluorescence emitted from the fluorescent label is measured.

  The evanescent wave leaking from the interface becomes stronger as the p-polarized component of the excitation light incident on the interface between the metal film and the dielectric medium increases. In addition, the s-polarized component of the excitation light incident on the interface between the metal film and the dielectric medium does not contribute to the emission of surface plasmon excitation fluorescence and causes autofluorescence of the dielectric medium. For this reason, in order to improve the measurement sensitivity and accuracy, the polarization component of the excitation light applied to the dielectric medium is adjusted so that the p-polarized component is incident exclusively on the interface between the metal film and the dielectric medium.

  On the other hand, when measurement by SPFS is performed, generally, an analysis chip including a dielectric medium is supported inside the measurement apparatus. Patent document 1 is an example. In Patent Document 1, a “transparent plate 17” that is a dielectric medium is sandwiched between “pressors 26 and 27”.

JP 2009-168594 A

  However, when stress is applied to the dielectric medium as in Patent Document 1, birefringence occurs in the dielectric medium, and the polarization direction of the excitation light incident on the interface between the metal film and the dielectric medium is disturbed. For this reason, the p-polarized component of the excitation light incident on the interface between the metal film and the dielectric medium is reduced, and the accuracy and sensitivity of measurement are reduced.

  The present invention is made to solve this problem. An object of the present invention is to provide a support structure and a measurement apparatus that improve the sensitivity and accuracy of measurement.

  The first to sixth aspects of the present invention relate to a support structure in a measurement apparatus that performs measurement by surface plasmon excitation fluorescence spectroscopy.

  In the first aspect of the present invention, the support structure includes a structure, a dielectric medium, a conductor film, and a support. The surface of the structure has a bonding region and a supported region. A sample accommodation space is formed in the structure. The sample storage space has an opening in the bonding region. The surface of the dielectric medium has an incidence area, a reflection area, and an emission area. The incident area, the reflection area, and the emission area are arranged so that the excitation light incident on the incident area is totally reflected by the reflection area and emitted from the emission area. The first main surface of the conductor film is bonded to the bonding region. The second main surface of the conductor film is in close contact with the reflective region. The support area of the support is in contact with the supported area. The support separates from the dielectric medium when the support area contacts the supported area.

  The second aspect of the present invention adds further matters to the first aspect of the present invention. In the second aspect of the present invention, the surface of the structure has a flat surface. The supported area and the bonding area are provided on a flat surface.

  The third aspect of the present invention adds further matters to the second aspect of the present invention. In the third aspect of the present invention, the support is provided with a positioning structure that restricts the movement of the structure in a direction parallel to the joining region.

  The fourth aspect of the present invention adds further matters to the third aspect of the present invention. In the fourth aspect of the present invention, a positioning pin that protrudes from the support region and extends perpendicularly to the support region is provided on the support. A positioning hole into which a positioning pin is inserted when the supporting region comes into contact with the supported region is formed in the structure.

  The fifth aspect of the present invention adds further matters to the third aspect of the present invention. In the fifth aspect of the present invention, the positioning structure is a positioning groove for accommodating a structure.

  The sixth aspect of the present invention adds further matters to the first aspect of the present invention. In the sixth aspect of the present invention, the surface of the structure has a first flat surface, a second flat surface, and a third flat surface. The second flat surface and the third flat surface are inclined from a direction perpendicular to the first flat surface. The distance between the second flat surface and the third flat surface becomes narrower as it approaches the first flat surface. The above supported area is a first supported area, and the surface of the structure has a second supported area. Said support area | region is a 1st support area | region, and a support body has a 2nd support area | region. The first supported region is on the second flat surface. The second supported region is on the third flat surface. The junction region is on the first flat surface. The second support area is in contact with the second supported area.

  7th aspect of this invention is related with the measuring device which performs the measurement by surface plasmon excitation fluorescence spectroscopy. In the seventh aspect of the present invention, a measurement mechanism and the support structure of the first aspect of the present invention are provided. The measurement mechanism causes excitation light to enter the incident surface and performs measurement by surface plasmon excitation fluorescence spectroscopy.

  According to the first and seventh aspects of the present invention, the stress applied to the dielectric medium is reduced, and the sensitivity and accuracy of measurement are improved.

  According to the third to sixth aspects of the present invention, the position of the structure is determined, and the dielectric medium is disposed at an appropriate position.

  These and other objects, features, aspects and advantages of the invention will become more apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.

It is a schematic diagram of the measuring apparatus of 1st Embodiment. It is a perspective view of the support structure of a 1st embodiment. It is sectional drawing of the support structure of 1st Embodiment. It is a perspective view of the analysis chip of a 1st embodiment. It is an exploded sectional view of the analysis chip of a 1st embodiment. It is a perspective view of the support body of 1st Embodiment. It is a figure which shows the relationship between a reaction area | region, a measurement area | region, and an irradiation area | region. It is a flowchart of the procedure of measurement. It is a perspective view of the support structure of 2nd Embodiment. It is sectional drawing of the support structure of 2nd Embodiment. It is a perspective view of the analysis chip of a 2nd embodiment. It is a perspective view of the support body of 2nd Embodiment. It is a perspective view of the support structure of 3rd Embodiment. It is sectional drawing of the support structure of 3rd Embodiment. It is a perspective view of the analysis chip of a 3rd embodiment. It is a perspective view of the support body of 3rd Embodiment. It is a perspective view of the support structure of 4th Embodiment. It is sectional drawing of the support structure of 4th Embodiment. It is a perspective view of the analysis chip of a 4th embodiment. It is a perspective view of the support body of 4th Embodiment. It is a perspective view of the support structure of 5th Embodiment. It is sectional drawing of the support structure of 5th Embodiment. It is a perspective view of the analysis chip of a 5th embodiment. It is a perspective view of the support body of 5th Embodiment. It is a perspective view of the support structure of 6th Embodiment. It is sectional drawing of the support structure of 6th Embodiment. It is a perspective view of the analysis chip of a 6th embodiment. It is a perspective view of the support body of 6th Embodiment. It is a perspective view of the support structure of 7th Embodiment. It is sectional drawing of the support structure of 7th Embodiment. It is a perspective view of the analysis chip of a 7th embodiment. It is a perspective view of the support body of 7th Embodiment.

{First embodiment}
(Outline of measuring device)
The first embodiment relates to a measurement device and a support structure.

  The schematic diagram of FIG. 1 shows the measuring apparatus of the first embodiment. 2 and 3 show the support structure of the first embodiment. 2 is a perspective view, and FIG. 3 is a cross-sectional view. The schematic diagram of FIG. 4 is a perspective view of the analysis chip of the first embodiment. The schematic diagram of FIG. 5 is an exploded sectional view of the analysis chip of the first embodiment. The schematic diagram of FIG. 6 is a perspective view of the support body of 1st Embodiment.

  The measurement apparatus 1000 of the first embodiment performs measurement by surface plasmon excitation fluorescence spectroscopy (SPFS).

  As shown in FIG. 1, the measurement apparatus 1000 includes an analysis chip 1002, a support body 1004, a pressing mechanism 1006, a reagent chip 1008, a measurement mechanism 1010, a liquid feeding mechanism 1012, a light absorber 1014, a control unit 1016, and a display unit 1018. Prepare. The analysis chip 1002 and the reagent chip 1008 are exchanged for each sample. The analysis chip 1002 is also called a sensor chip, an inspection chip, a sample cell, or the like.

  The measurement mechanism 1010 includes a laser diode unit 1020, a laser diode unit driving mechanism 1022, a first bandpass filter 1024, a low-pass filter 1026, a neutral density (ND) filter 1028, a half-wave plate 1030, a half-wave plate driving mechanism 1032, and a shaping. An optical system 1034, a condenser lens 1036, a second bandpass filter 1038, a bandpass filter driving mechanism 1040, an imaging lens 1042, and a photomultiplier tube (PMT) 1044 are provided.

  The first bandpass filter 1024, the low-pass filter 1026, the neutral density filter 1028, the half-wave plate 1030, and the shaping optical system 1034 constitute an excitation optical system 1046. The condenser lens 1036, the second band pass filter 1038, and the imaging lens 1042 constitute a detection optical system 1048.

  The laser diode unit 1020 includes a laser diode 1050, a posture holding mechanism 1052, a beam splitter 1054, a photodiode 1056, and a temperature adjustment circuit 1058.

  The liquid feeding mechanism 1012 includes a liquid feeding pump 1060 and a liquid feeding pump drive mechanism 1062.

  As shown in FIGS. 2 and 3, the support structure 1100 of the first embodiment includes an analysis chip 1002, a support body 1004, and a pressing mechanism 1006.

  As shown in FIGS. 4 and 5, the analysis chip 1002 includes a gold film 1064, a prism 1066, a capturing body 1068, and a flow path forming body 1070.

  As shown in FIG. 6, the support body 1004 includes a base 1102 and support legs 1104a and 1104b.

(Outline of measurement)
When measurement is performed, as shown in FIGS. 2 and 3, the analysis chip 1002 is supported by the support body 1004, the analysis chip 1002 is pressed against the support body 1004 by the pressing mechanism 1006, and the analysis chip 1002 is measured. Fixed to. When the analysis chip 1002 is supported by the support 1004, the flow path forming body 1070 is supported by the support 1004, and the prism 1066 is separated from the support 1004. When the prism 1066 is not in contact with the support 1004, stress is not easily applied to the prism 1066, and birefringence is unlikely to occur in the prism 1066. Thereby, the polarization direction of the excitation light EL is hardly disturbed, and the sensitivity and accuracy of measurement are improved. Further, in the case where the prism 1066 is not supported by the support body 1004, it is not necessary to provide a structure for supporting the prism 1066, and the shape of the prism 1066 is simplified. The simplification of the shape of the prism 1066 contributes to reducing unevenness in density during molding and making it difficult for birefringence to occur.

  In a state where the analysis chip 1002 is supported by the support body 1004, the sample liquid 1092 is supplied to the flow path 1072 formed in the flow path forming body 1070 as shown in FIG. By the antigen-antibody reaction, the antigen contained in the sample liquid 1092 is captured by the capturing body 1068, and the captured antigen is fluorescently labeled with the fluorescently labeled antibody contained in the sample liquid 1092.

  In parallel with the antigen-antibody reaction, the excitation light EL is irradiated onto the prism 1066. The irradiated excitation light EL is reflected at the interface between the prism 1066 and the gold film 1064.

  When the excitation light EL is reflected at the interface between the prism 1066 and the gold film 1064, an evanescent wave leaks from the interface between the gold film 1064 and the prism 1066 toward the gold film 1064, and plasmons on the surface of the gold film 1064. And the evanescent wave interfere. When the plasmon and the evanescent wave resonate, the electric field of the evanescent wave is remarkably enhanced. The enhanced electric field excites the fluorescent label, and surface plasmon excitation fluorescence FL is emitted from the fluorescent label. The amount of surface plasmon excitation fluorescence FL is measured by a photomultiplier tube 1044. From the measurement result of the photomultiplier tube 1044, the presence / absence of the antigen, the capture amount of the antigen, and the like are calculated by the control unit 1016, and the calculation result is displayed on the display unit 1018.

(Shape of the flow path forming body)
As shown in FIGS. 4 and 5, the outer shape of the flow path forming body 1070 is a rectangular parallelepiped or a cube, and the surface 1101 of the flow path forming body 1070 has a flat upper surface 1102, a side surface 1104, and a lower surface 1106. A bonding area 1108 and an exposed area 1112 are provided on the surface 1101 of the flow path forming body 1070, and supported areas 1110a and 1110b are set. The bonding region 1108 is a region bonded to the first main surface 1114 of the gold film 1064 and occupies a part of the lower surface 1106. The exposed region 1112 is a region exposed to the outside of the analysis chip 1002 and occupies a part of the upper surface 1102 and the side surface 1104. The supported regions 1110 a and 1110 b are regions supported by the support body 1004 and occupy a part of the lower surface 1106. In FIG. 4, hatching is drawn in the supported regions 1110a and 1110b. The arrangement of the bonding region 1108, the exposed region 1112 and the supported regions 1110a and 1110b may be changed. The outer shape of the flow path forming body 1070 may be other than a rectangular parallelepiped and a cube. When the outer shape of the flow path forming body 1070 is other than a rectangular parallelepiped and a cube, the bonding region 1108 and the supported regions 1110a and 1110b are provided in a concentrated manner on a flat surface facing a certain direction such as the lower surface 1106. The flat surface on which the bonding region 1108 is provided and the flat surface on which the supported regions 1110a and 1110b are set may face different directions.

(Prism shape)
The external shape of the prism 1066 is a semi-cylindrical body, and the surface 1118 of the prism 1066 has a circumferential side surface 1120 and a flat side surface 1122. On the surface 1118 of the prism 1066, an incident area 1124, a reflection area 1126, and an emission area 1128 of the excitation light EL are set. The incident area 1124 and the emission area 1128 occupy a part of the circumferential side surface 1120. The reflective region 1126 occupies a part of the flat side surface 1122. The incident area 1124, the reflection area 1126, and the emission area 1128 are arranged so that the excitation light EL incident on the incident area 1124 is totally reflected by the reflection area 1126 and emitted from the emission area 1128. When the incident region 1124 occupies a part of the circumferential side surface 1120, the excitation light EL incident at different incident angles is collected, and the influence of the change in the resonance angle is less likely to appear.

  Desirably, the entrance region 1124 and the exit region 1128 are arranged symmetrically. As a result, the s-polarized component of the reflected light is less likely to stay inside the prism 1066.

  As long as the excitation light EL is incident on the reflection region 1126 at the resonance angle, the external shape of the prism 1066 may be other than a semi-cylindrical body, and the prism 1066 may be replaced with a shape that is not included in the category of “prism”. For example, the external shape of the prism 1066 may be a trapezoidal column, a plate, or the like.

(Whole analysis chip)
The capturing body 1068 is fixed to the first main surface 1114 of the gold film 1064. The first main surface 1114 of the gold film 1064 is bonded to the bonding region 1108. Second main surface 1116 of gold film 1064 is in close contact with reflection region 1126. The capturing body 1068 is accommodated in the flow path 1072. When the antigen is directly captured on the first main surface 1114 of the gold film 1064, the capturing body 1068 may be omitted.

  The gold film 1064 and the flow path forming body 1070 are joined by adhesion, laser welding, ultrasonic welding, clamp pressure bonding, or the like. However, the gold film 1064 and the flow path forming body 1070 may be joined by other methods.

  The gold film 1064 is formed in the reflective region 1126 by sputtering, vapor deposition, plating, or the like. However, the gold film 1064 may be formed by other methods.

(Material of flow path forming body)
The flow path forming body 1070 is made of a material transparent to the surface plasmon excitation fluorescence FL. The flow path forming body 1070 is preferably made of resin and manufactured by injection molding. The thickness of the flow path forming body 1070 is desirably 1 to 10 mm. “Thickness” is a dimension in a direction perpendicular to the bonding region 1108. When the thickness is less than this range, the rigidity of the flow path forming body 1070 decreases, and it becomes difficult for the flow path forming body 1070 to receive stress. When the thickness exceeds this range, the time required for forming the flow path forming body 1070 becomes longer, and the manufacturing cost of the analysis chip increases.

(Prism material)
The prism 1066 is a dielectric medium made of a material transparent to the excitation light EL. Desirably, the prism 1066 is made of glass or resin having a refractive index of 1.4 to 1.6. When the prism 1066 is made of resin, the prism 1066 is desirably manufactured by injection molding. However, the prism 1066 may be manufactured by other methods. The material of the prism 1066 is desirably a resin that hardly causes birefringence. However, according to the support structure 1100 of the first embodiment, since stress is not easily applied to the prism 1066, even when the prism 1066 is made of a resin that easily generates birefringence, the accuracy and sensitivity of measurement are not easily lowered.

(Gold film size and material)
The gold film 1064 is a thin film. The film thickness of the gold film 1064 is desirably 30 to 70 nm. However, the film thickness of the gold film 1064 may be outside this range.

  The gold film 1064 may be replaced with a film made of a conductor that generates surface plasmon resonance other than gold. For example, the gold film 1064 may be replaced with a film made of a metal such as silver, copper, or aluminum, or an alloy containing these metals.

(Flow path)
A flow path 1072 is formed in the flow path forming body 1070. The channel 1072 extends from one sample solution inlet / outlet 1130 to the other sample solution inlet / outlet 1132 via the inside of the channel forming body 1070, and provides a sample solution storage space for storing the sample solution 1092. Sample liquid inlets / outlets 1130 and 1132 are provided in the exposed region 1112. As a result, the sample liquid 1092 can be supplied to the sample liquid inlets / outlets 1130 and 1132.

  The channel 1072 includes a surface exposed channel 1136 and internal through channels 1138 and 1140.

  The surface exposed flow channel 1136 extends along the bonding region 1108 and has an opening 1134 in the bonding region 1108. Thus, when the sample liquid 1092 is supplied to the surface exposed flow path 1136, the sample liquid 1092 is supplied to the first main surface 1114, and the sample liquid 1092 is fixed to the capturing body 1068 fixed to the first main surface 1114. Contact.

  One internal through channel 1138 extends from one sample liquid inlet / outlet port 1130 to one end of the surface exposed channel 1136. The other internal through channel 1140 extends from the other sample liquid inlet / outlet port 1132 to the other end of the surface exposed channel 1136. When the sample solution 1092 is supplied to the sample solution inlet / outlet 1130 or 1132 by the internal through channels 1138 and 1140, the sample solution 1092 is supplied to the surface exposed channel 1136. The number of sample liquid inlets / outlets may be increased to three or more. The channel 1072 may be replaced with a reservoir having one sample solution inlet / outlet.

(Combination of flow path forming body)
The flow path forming body 1070 is composed of one structure. However, the flow path forming body 1070 may be a combination of two or more structures. For example, the flow path forming body 1070 may be a combination of a seal in which the surface exposed flow path 1136 is formed and a block in which the internal through flow paths 1138 and 1140 are formed.

(Captured body)
The capturing body 1068 is made of a non-fluid body. Therefore, even if the sample liquid 1092 contacts the capturing body 1068, the capturing body 1068 does not move.

  The capturing body 1068 includes an antibody that binds to the antigen to be detected. The antibody is evenly distributed. When the sample liquid 1092 containing the antigen to be detected comes into contact with the capturing body 1068, the antigen to be detected contained in the sample liquid 1092 binds to the antibody contained in the capturing body 1068, and the detection target contained in the sample liquid 1092 is detected. The antigen is captured by the capturing body 1068.

  The capturing body 1068 is desirably fixed to the first main surface 1114 by surface treatment.

(Support)
As shown in FIG. 6, the support body 1004 is a bifurcated branch body in which support legs 1104 a and 1104 b having a plate shape branch from the base 1102. The support legs 1104a and 1104b may have a shape other than the plate shape. The base 1102 is fixed inside the measurement apparatus 1000. The support legs 1104a and 1104b extend upward in the vertical direction from the base 1102. A part of the upper surface 1250a at the tip of the support leg 1104a and a part of the upper surface 1250b at the tip of the support leg 1104b become support regions 1200a and 1200b, respectively. When the support body 1004 supports the analysis chip 1002, the support areas 1200a and 1200b are in contact with the supported areas 1110a and 1110b, respectively. Support areas 1200a and 1200b are flat and at the same height.

  The support body 1004 has a shape that does not contact the prism 1066 when the analysis chip 1002 is supported. This makes it difficult for stress to be applied to the prism 1066, and makes it difficult for birefringence to occur in the prism 1066, improving the sensitivity and accuracy of measurement. The support 1004 has a shape that does not block the excitation light EL reflected by the excitation light EL and the reflection region 1126, that is, the reflected light RL, when the analysis chip 1002 is supported.

  The gap between one support leg 1104 a and the other support leg 1104 b is wider than the width of the prism 1066 and narrower than the width of the flow path forming body 1070. “Width” is a dimension in a direction perpendicular to the optical path of the excitation light EL. For this reason, one supported region 1110 a is along one opposite side of the lower surface 1106, and the other supported region 1110 b is along the other opposite side of the lower surface 1106. The gold film 1064 is bonded between one supported region 1110a and the other supported region 1110b. Accordingly, the heavy prism 1066 is supported between the one supported region 1110a and the other supported region 1110b, and the flow path forming body 1070 is stably supported. However, the bonding region 1108 may be provided in another place. The number of support legs may be reduced to one, and the number of support areas and supported areas may be reduced to one. The number of support legs may be increased to 3 or more, and the number of support areas and supported areas may be increased to 3 or more.

(Pressing mechanism)
The pressing mechanism 1006 includes a pressing element 1142. The pressing mechanism 1006 applies the pressing element 1142 to the analysis chip 1002 and presses the analysis chip 1002 toward the support body 1004. The pressing element 1142 is preferably made of an elastic body such as rubber and contacts the upper surface 1102 of the flow path forming body 1070. Thereby, when the analysis chip 1002 is pressed, the flow path forming body 1070 is hardly damaged. The pressing mechanism 1006 may be omitted, and the analysis chip 1002 may simply be placed on the support body 1004. The pressing mechanism 1006 is disposed at a location that does not interfere with the surface plasmon excitation fluorescence FL.

(Optical path of excitation light and reflected light)
As shown in FIG. 1, the excitation light EL is guided from the laser diode unit 1020 to the incident region 1124 by the excitation optical system 1046. The excitation light EL sequentially passes through the first bandpass filter 1024, the linear polarization filter 1026, the neutral density filter 1028, the half-wave plate 1030, and the shaping optical system 1034. The reflected light RL is absorbed by the light absorber 1014 provided in the vicinity of the emission region 1128. As a result, the reflected light RL is less likely to affect the measurement.

(Laser diode unit)
In the laser diode unit 1020, the beam emitted from the laser diode 1050 is split into a main beam and a sub beam by the beam splitter 1054. The main beam becomes the excitation light EL.

  The cross-sectional shape of the beam of the excitation light EL is a flat shape. In order to make the irradiation shape of the excitation light EL to the reflective region 1126 close to a circle, the laser diode 1050 is oriented in such a posture that an elliptical short axis is included in a plane that includes the optical path of the excitation light EL and is perpendicular to the reflective region 1126. It is held by the holding mechanism 1052.

  When the wavelength and amount of laser light emitted from the laser diode 1050 depend on temperature, the laser diode 1050 is desirably controlled by the temperature adjustment circuit 1058. For example, the light amount of the sub beam is measured by the photodiode 1056, and the power supplied to the laser diode 1050 is regressively controlled by the temperature adjustment circuit 1058 so that the measurement result of the light amount of the sub beam is maintained constant. Thereby, the temperature of the laser diode 1050 is kept constant, and the wavelength and light amount of the excitation light EL are kept constant. The photodiode 1056 may be replaced with another type of light amount sensor. For example, the photodiode 1056 may be replaced with a phototransistor, a photoresistor, or the like. Since the wavelength of the excitation light EL affects the resonance angle and the amount of evanescent wave oozing, the temperature adjustment circuit 1058 contributes to the improvement of measurement accuracy and sensitivity.

  When it takes a long time for the temperature of the laser diode 1050 to reach a steady temperature, power is constantly supplied to the laser diode 1050 from the start of the operation of the measuring apparatus 1000.

  The laser diode 1050 may be replaced with other types of light sources. For example, the laser diode 1050 may be replaced with a light emitting diode, a mercury lamp, a laser other than the laser diode, or the like. When the light emitted from the light source is not a beam, the light is converted into a beam by a lens, a mirror, a slit, or the like. When the light emitted from the light source is not monochromatic light, the light is converted into monochromatic light by a diffraction grating or the like. When the light emitted from the light source is not linearly polarized light, the light is converted into linearly polarized light by a polarizer or the like.

(First bandpass filter)
When the excitation light EL passes through the first bandpass filter 1024, the wavelength distribution of the excitation light EL is narrowed. Thereby, even if the wavelength distribution of the excitation light EL emitted from the laser diode unit 1020 is wide, the excitation light EL having a narrow wavelength distribution can be obtained. If the wavelength distribution of the excitation light EL emitted from the laser diode unit 1020 is sufficiently narrow, the first band pass filter 1024 may be omitted.

(Linear polarization filter)
When the excitation light EL passes through the linear polarization filter 1026, the distribution of the polarization direction of the excitation light EL is narrowed. Thereby, even if the distribution of the polarization direction of the excitation light EL emitted from the laser diode unit 1020 is wide, the excitation light EL having a narrow distribution of the polarization direction can be obtained. When the distribution of the polarization direction of the excitation light EL emitted from the laser diode unit 1020 is sufficiently narrow, the linear polarization filter 1026 may be omitted.

(Density filter)
When the excitation light EL passes through the neutral density filter 1028, the light amount of the excitation light EL is decreased. If the amount of excitation light EL emitted from the laser diode unit 1020 is appropriate, the neutral density filter 1028 may be omitted.

(Half wave plate and half wave plate drive mechanism)
The half-wave plate 1030 is rotated around a rotation axis perpendicular to the half-wave plate 1030 by the half-wave plate driving mechanism 1032. The half-wave plate driving mechanism 1032 rotates the half-wave plate 1030 by a rotary stepping motor or the like. The polarization direction of the excitation light EL that passes through the half-wave plate 1030 is adjusted by the rotation angle of the half-wave plate 1030. The polarization direction of the excitation light EL can be adjusted between the polarization direction in which the bleeding of the evanescent wave from the reflection region 1126 is maximized and the polarization direction in which the bleeding of the evanescent wave from the reflection region 1126 is eliminated. In the initial state, the rotation angle of the half-wave plate 1030 is set to the rotation angle at which the p-polarized component is expected to be incident on the reflection region 1126.

  The half-wave plate driving mechanism 1032 may be replaced with a mechanism that rotates the laser diode 1050 or the laser diode unit 1020 around the optical axis. When optimization of the polarization direction described later is omitted, the half-wave plate driving mechanism 1032 may be omitted and the half-wave plate 1030 may be fixed. When the optimization of the polarization direction described later is omitted and the laser diode 1050 or the laser diode unit 1020 is held in a posture in which the p-polarized component is mainly incident on the reflection region 1126, the half-wave plate 1030 and the half-wave plate drive are performed. The mechanism 1032 may be omitted.

(Shaping optics)
When the excitation light EL passes through the shaping optical system 1034, the beam size, cross-sectional shape, and the like of the excitation light EL are shaped by a slit, a zoom optical system, and the like.

(Optical path of surface plasmon excitation fluorescence)
The surface plasmon excitation fluorescence FL is guided from the capturing body 1068 to the photomultiplier tube 1044 by the detection optical system 1048. The surface plasmon excitation fluorescence FL sequentially passes through the condenser lens 1036, the second bandpass filter 1038, and the imaging lens 1042.

(Condensing lens and imaging lens)
The condensing lens 1036 condenses the surface plasmon excitation fluorescence FL and converts it into parallel light. The imaging lens 1042 images the surface plasmon excitation fluorescence FL onto the photomultiplier tube 1044. The condensing lens 1036 and the imaging lens 1042 constitute a conjugate optical system. Thereby, the influence of stray light is suppressed.

(Second bandpass filter and bandpass filter drive mechanism)
The second band pass filter 1038 is inserted into and removed from the optical path of the measurement light between the condenser lens 1036 and the imaging lens 1042 by the band pass filter driving mechanism 1040. “Measurement light” is scattered light of excitation light EL and surface plasmon excitation fluorescence FL.

  When the amount of light of the surface plasmon excitation fluorescence FL is measured, a second bandpass filter 1038 is inserted into the optical path of the measurement light, and the second bandpass filter 1038 selectively selects light having the same wavelength as the excitation light EL. Attenuated. Thereby, the scattered light is attenuated, and the surface plasmon excitation fluorescence FL is mainly guided to the photomultiplier tube 1044, and the sensitivity and accuracy of measurement are improved. When the amount of scattered light is measured, the second bandpass filter 1038 is removed from the optical path of the measurement light.

  A neutral density filter may be inserted into and removed from the optical path of the measurement light. When the light amount of the surface plasmon excitation fluorescence FL is measured, the neutral density filter is removed from the optical path of the measurement light. When the amount of scattered light is measured, a neutral density filter is inserted into the optical path of the measurement light. Thereby, the difference between the light amounts of the surface plasmon excitation fluorescence FL and the scattered light guided to the photomultiplier tube 1044 is reduced, and the light amount can be easily measured. The light amount of the surface plasmon excitation fluorescence FL may be measured by a relatively high sensitivity photomultiplier tube 1044, and the light amount of scattered light may be measured by a relatively low sensitivity photodiode, phototransistor, photoresistor, or the like.

(Photomultiplier tube)
The amount of measurement light is measured by a photomultiplier tube 1044. The photomultiplier tube 1044 has the advantage of good sensitivity and signal-to-noise (S / N) ratio. However, the photomultiplier tube 1044 may be replaced with another type of light quantity sensor. For example, the photomultiplier tube 1044 may be replaced with a cooled charge coupled device (CCD) camera or the like.

(Liquid feeding mechanism)
In the liquid feeding mechanism 1012, the liquid feeding pump 1060 sucks the liquid feeding object from the liquid feeding source and discharges it to the liquid feeding destination. The liquid feeding pump 1060 is conveyed from the liquid feeding source to the liquid feeding destination by the liquid feeding pump driving mechanism 1062. The liquid delivery object may be fed by a tube.

(Control part)
The control unit 1016 is an embedded computer that executes software. One embedded computer may serve the function of the control unit 1016, or two or more embedded computers may share the function of the control unit 1016. Hardware without software may be responsible for all or part of the function of the control unit 1016. The hardware may be an electronic circuit such as an operational amplifier or a comparator, or may be a mechanical mechanism such as a link mechanism.

(Relationship between reaction area, measurement area and irradiation area)
The schematic diagram of FIG. 7 is a plan view showing a desirable relationship among the irradiation region 1300, the measurement region 1302, and the reaction region 1304 in the reflection region 1126. The irradiation region 1300 is a region where the excitation light EL is irradiated. The measurement region 1302 is a region where the amount of measurement light is measured by the photomultiplier tube 1044. The reaction region 1304 is a region where the capturing body 1068 is provided and the antigen-antibody reaction proceeds. The planar shapes of the irradiation region 1300 and the measurement region 1302 are preferably circular.

  The irradiation region 1300 and the measurement region 1302 overlap at least. Desirably, the irradiation region 1300 is included in the measurement region 1302, and more desirably, the irradiation region 1300 is disposed in the center of the measurement region 1302. Thereby, even if the irradiation position is shifted due to the variation of the prism 1066 or the like, the irradiation region 1300 does not easily deviate from the measurement region 1302, and the amount of measurement light is maintained.

  The irradiation region 1300 and the reaction region 1304 overlap at least, preferably the irradiation region 1300 is included in the reaction region 1304, and more preferably, the irradiation region 1300 is disposed at the center of the reaction region 1304.

  The measurement region 1302 and the reaction region 1304 overlap at least, preferably the measurement region 1302 is included in the reaction region 1304, and more preferably, the measurement region 1302 is disposed in the center of the reaction region 1304.

(Measurement procedure)
The flowchart of FIG. 8 shows a measurement procedure. In the measurement apparatus 1000, measurement is performed while the antigen-antibody reaction is in progress.

(Preparation and mounting of analysis chip and reagent chip)
As shown in FIG. 8, an analysis chip 1002 and a reagent chip 1008 are prepared, and the analysis chip 1002 and the reagent chip 1008 are attached to the measuring device 1000 (step S101). The reagent chip 1008 is disposed in the pretreatment chamber. The specimen 1084 is stored in the specimen container 1073 of the reagent chip 1008 when the reagent chip 1008 is prepared. The specimen 1084 is typically a collected material from a human such as blood, but may be a collected material from a non-human organism or a non-living material. Diluent liquid 1086, fluorescent labeling liquid 1088, and cleaning liquid 1090 are previously stored in diluent container 1074, fluorescent labeling liquid container 1076, and cleaning liquid container 1078 of reagent chip 1008, respectively. It is planned that the sample liquid 1092 is accommodated in the dilution container 1082 of the reagent chip 1008.

(Preparation of sample solution)
After the analysis chip 1002 and the reagent chip 1008 are attached to the measuring apparatus 1000, the specimen 1084 is sent from the specimen container 1073 to the dilution container 1082, and the dilution liquid 1086 is sent from the dilution liquid container 1074 to the dilution container 1082, so that the fluorescence is emitted. The fluorescent labeling liquid 1088 is sent from the labeling liquid container 1076 to the dilution container 1082. Thereby, the sample liquid 1092 is prepared in the dilution container 1082 (step S102). The components of the sample liquid 1092 may be changed.

  In some cases, dilution of the specimen 1084 may be omitted. In addition to or in place of dilution, other pretreatments such as blood cell separation and reagent mixing may be performed.

(Optimization of irradiation position)
After the sample liquid 1092 is prepared, the irradiation position is preferably optimized (step S103). However, the optimization of the irradiation position may be omitted. The irradiation position may be optimized before the sample liquid 1092 is prepared or in parallel with the sample liquid 1092 being prepared.

  In the irradiation position optimization, the laser diode unit driving mechanism 1022 is controlled by the control unit 1016. The laser diode unit driving mechanism 1022 drives the laser diode unit 1020 to translate the excitation light EL. Thereby, the irradiation position is scanned along a straight line. During scanning of the irradiation position, the amount of scattered light is measured by the photomultiplier tube 1044. The measurement result of the amount of scattered light is transferred to the control unit 1016. While the amount of scattered light is being measured, the second band-pass filter 1038 is removed from the optical path of the measurement light. A mirror that reflects the excitation light EL may be provided, and the irradiation position may be scanned by driving the mirror. In addition to the laser diode unit 1020, the excitation optical system 1046 may be driven.

  In the section where the irradiation region 1300 is included in the measurement region 1302, the amount of scattered light is substantially constant. However, outside the section, the irradiation area 1300 deviates from the measurement area 1302, and the amount of scattered light decreases as the irradiation position moves away from the section. The control unit 1016 specifies first and second positions where the amount of scattered light decreases from the maximum value by the same value, and determines an intermediate position between the first and second positions. The laser diode unit driving mechanism 1022 moves the laser diode unit 1020 to a position intermediate between the first and second positions.

  At the resonance angle, the amount of the reflected light RL is small, and the reflected light RL hardly generates autofluorescence emitted from the prism 1066. For this reason, the optical path length of the excitation light EL in the measurement region 1302 greatly affects the amount of autofluorescence, and the amount of autofluorescence changes as the irradiation position changes. The amount of autofluorescence is small compared to the amount of excitation light EL, but cannot be ignored compared to the amount of surface plasmon excitation fluorescence FL. However, since the amount of autofluorescence is small, measurement of the amount of light of the surface plasmon excitation fluorescence FL only affects autofluorescence emitted from the vicinity of the reflection region 1126.

  When the irradiation region 1300 is arranged at the center of the measurement region 1302 by optimizing the irradiation position, the optical path length of the excitation light EL in the measurement region 1302 is constant, the influence of the amount of autofluorescence is constant, and the measurement Sensitivity and accuracy are improved. Desirably, optimization of an irradiation position is performed before measurement of the amount of autofluorescence. Thereby, the accuracy of measurement of the amount of autofluorescence is improved.

(Measurement of the amount of autofluorescence)
After the irradiation position is optimized, the amount of autofluorescence is measured by the photomultiplier tube 1044 (step S104). The measurement result of the amount of autofluorescence is transferred to the control unit 1016 and stored in the control unit 1016.

(Optimization of excitation light polarization direction)
After the amount of autofluorescence is measured, the polarization direction of the excitation light EL is optimized (step S105).

  In optimizing the polarization direction of the excitation light EL, the half-wave plate driving mechanism 1032 is controlled by the control unit 1016. The half-wave plate driving mechanism 1032 drives the half-wave plate 1030 to rotate the polarization direction of the excitation light EL. Thereby, the polarization direction of the excitation light EL is scanned. The amount of scattered light is measured by the photomultiplier tube 1044 during scanning of the excitation light EL in the polarization direction. The measurement result of the amount of scattered light is transferred to the control unit 1016. While the amount of scattered light is being measured, the second band-pass filter 1038 is removed from the optical path of the measurement light.

  The control unit 1016 specifies the rotation angle at which the amount of scattered light is maximized. Half-wave plate driving mechanism 1032 rotates half-wave plate 1030 to a rotation angle at which the amount of scattered light is maximized.

  Birefringence that cannot be ignored occurs when light travels through a resin medium. This birefringence is caused by a change in the density of the medium depending on the position. Since the change in the density of the medium depending on the position occurs at the time of molding the resin, the birefringence strength differs for each prism 1066. For this reason, depending on the prism 1066, even if only the p-polarized light component that contributes to the exudation of the evanescent wave is incident on the reflection region 1126, the s-polarized light component is generated and the p-polarized light component is reduced. Decreases.

  By optimizing the polarization direction of the excitation light EL, the decrease of the p-polarized component due to the variation of the prism 1066 is eliminated, and the measurement sensitivity and accuracy are improved.

(Measurement of dark noise)
After the polarization direction of the excitation light EL is optimized, the amount of dark noise is measured by the photomultiplier tube 1044 (step S106). The measurement result of the dark noise amount is transferred to the control unit 1016 and stored in the control unit 1016. While the amount of dark noise is being measured, the second band pass filter 1038 is inserted into the optical path of the measurement light.

(Measurement of antigen-antibody reaction and surface plasmon excitation fluorescence)
After the dark noise amount is measured, the sample liquid 1092 is injected into the flow path 1072. In parallel with the antigen-antibody reaction, the light quantity of the surface plasmon excitation fluorescence FL is measured by the photomultiplier tube 1044 (step S107).

  In injecting the sample liquid 1092 into the flow path 1072, the liquid feeding mechanism 1012 is controlled by the control unit 1016. The liquid feeding mechanism 1012 sends the sample liquid 1092 from the dilution container 1082 to the flow path 1072. Thereby, the antigen-antibody reaction proceeds, the antigen is captured by the capturing body 1068, and the captured antigen is fluorescently labeled on the fluorescently labeled antibody.

  The measurement result of the light amount of the surface plasmon excitation fluorescence FL during the antigen-antibody reaction is transferred to the control unit 1016 and stored in the control unit 1016. While the light quantity of the surface plasmon excitation fluorescence FL is being measured, the second bandpass filter 1038 is inserted into the optical path of the measurement light.

  The light quantity of the surface plasmon excitation fluorescence FL is measured in a state where the liquid feeding pump 1060 is inserted into the sample liquid inlet / outlet 1130 or 1132. When the analysis chip 1002 is supported by the support body 1004, the stress applied from the liquid feed pump 1060 is received by the flow path forming body 1070, and no stress is applied to the prism 1066. Therefore, the support structure 1100 of the first embodiment is particularly suitable for measuring the light amount of the surface plasmon excitation fluorescence FL during the progress of the antigen-antibody reaction. However, the support structure 1100 of the first embodiment is also useful when the light amount of the surface plasmon excitation fluorescence FL is measured after completion of the antigen-antibody reaction.

(Correction of measurement results)
After the light amount of the surface plasmon excitation fluorescence FL is measured, the control unit 1016 performs correction to subtract the measurement result of the autofluorescence light amount and the measurement result of the dark noise amount from the measurement result of the light amount of the surface plasmon excitation fluorescence FL (step) S108) Thereby, the influence of autofluorescence and dark noise is suppressed, and the sensitivity and accuracy of measurement are improved. The correction of the measurement result may be omitted. When the correction of the measurement result is omitted, the measurement of the amount of autofluorescence and the measurement of the amount of dark noise are also omitted.

(Memory and display)
The corrected measurement result of the light amount of the surface plasmon excitation fluorescence FL is stored in the control unit 1016 together with the sample number and the like, and is displayed on the display unit 1018 together with the sample number and the like (step S109). The measurement result of the light amount of the surface plasmon excitation fluorescence FL is converted into the absolute amount, concentration, etc. of the antigen as necessary.

(Initialize)
After storing and displaying the measurement result, the measuring apparatus 1000 is initialized (step S110). In the initialization of the measuring apparatus 1000, a movable object such as the half-wave plate 1030 is returned to the initial position.

  Among the above procedures, a procedure executed by the measuring apparatus 1000 may be executed manually, or a procedure executed by the manual operation may be executed by the measuring apparatus 1000.

  The incident angle of the excitation light EL to the reflection region 1126 may be scanned near the resonance angle, and the incident angle may be optimized.

{Second Embodiment}
The second embodiment relates to a support structure that is employed instead of the support structure of the first embodiment.

  The schematic views of FIGS. 9 and 10 show the support structure of the second embodiment. FIG. 9 is a perspective view, and FIG. 10 is a cross-sectional view. The schematic diagram of FIG. 11 is a perspective view of the analysis chip of the second embodiment. The schematic diagram of FIG. 12 is a perspective view of the support body of 2nd Embodiment.

  As shown in FIGS. 9 and 10, the support structure 2100 of the second embodiment includes an analysis chip 2002, a support body 2004, and a pressing mechanism 2006. The analysis chip 2002 and the pressing mechanism 2006 of the second embodiment are the same as the analysis chip 1002 and the pressing mechanism 1006 of the first embodiment, respectively.

  As shown in FIG. 11, the analysis chip 2002 of the second embodiment includes a gold film 2064, a prism 2066, a capturing body 2068, and a flow path forming body 2070. The gold film 2064, the prism 2066, the capturing body 2068, and the flow path forming body 2070 of the second embodiment are the same as the gold film 1064, the prism 1066, the capturing body 1068, and the flow path forming body 1070 of the first embodiment, respectively. is there. The analysis chip 2002 of the second embodiment is different from the analysis chip 1002 of the first embodiment in that the locations where the supported regions 2110a, 2110b, 2110c, and 2110d are set are different.

  As shown in FIG. 12, the support body 2004 of the second embodiment includes a base 2102 and support legs 2104a, 2104b, 2104c, and 2104d. The base 2102 of the second embodiment is the same as the base 1102 of the first embodiment. The support body 2004 of the second embodiment is different from the support body 1004 of the first embodiment in that the support legs 1104a and 1104b are replaced with the support legs 2104a, 2104b, 2104c, and 2104d.

  The support body 2004 is a four-forked body in which support legs 2104 a, 2104 b, 2104 c, and 2104 d having a bar shape branch from the base 2102. The support legs 2104a, 2104b, 2104c, and 2104d extend upward in the vertical direction from the base 2102. A part of the upper surface 2250a at the tip of the support leg 2104a, a part of the upper surface 2250b at the tip of the support leg 2104b, a part of the upper surface 2250c at the tip of the support leg 2104c, and a part of the upper surface 2250d at the tip of the support leg 2104d The parts become support areas 2200a, 2200b, 2200c and 2200d, respectively. When the support 2004 supports the analysis chip 2002, the support areas 2200a, 2200b, 2200c, and 2200d are in contact with the supported areas 2110a, 2110b, 2110c, and 2110d, respectively. Support regions 2200a, 2200b, 2200c and 2200d are flat and at the same height. The supported regions 2110 a, 2110 b, 2110 c, and 2110 d are in the vicinity of the four corners of the lower surface 2106.

  The support 2004 has a shape that does not contact the prism 2066 when the analysis chip 2002 is supported. This makes it difficult for stress to be applied to the prism 2066, making it difficult for birefringence to occur in the prism 2066, and improving the sensitivity and accuracy of measurement. In addition, the support 2004 has a shape that does not block the excitation light EL and the reflected light RL when the analysis chip 2002 is supported.

{Third embodiment}
The third embodiment relates to a support structure that is employed instead of the support structure of the first embodiment.

  The schematic diagrams of FIGS. 13 and 14 show the support structure of the third embodiment. FIG. 13 is a perspective view, and FIG. 14 is a cross-sectional view. The schematic diagram of FIG. 15 is a perspective view of the analysis chip of the third embodiment. The schematic diagram of FIG. 16 is a perspective view of the support body of 3rd Embodiment.

  As shown in FIGS. 13 and 14, the support structure 3100 of the third embodiment includes an analysis chip 3002, a support body 3004, and a pressing mechanism 3006. The pressing mechanism 3006 of the third embodiment is the same as the pressing mechanism 1006 of the first embodiment.

  As shown in FIG. 15, the analysis chip 3002 of the third embodiment includes a gold film 3064, a prism 3066, a capturing body 3068, and a flow path forming body 3070. The gold film 3064, the prism 3066, and the capturing body 3068 of the third embodiment are the same as the gold film 1064, the prism 1066, and the capturing body 1068 of the first embodiment, respectively. The flow path forming body 3070 of the third embodiment is different from the flow path forming body 1070 of the first embodiment in that positioning holes 3304 and 3306 are formed.

  As shown in FIG. 16, the support body 3004 of the third embodiment includes a base 3102, support legs 3104 a and 3104 b, and positioning pins 3300 and 3302. The base 3102 and the support legs 3104a and 3104b of the third embodiment are the same as the base 1102 and the support legs 1104a and 1104b of the first embodiment, respectively. The support body 3004 of the third embodiment is different from the support body 1004 of the first embodiment in that positioning pins 3300 and 3302 are further provided.

  A part of the upper surface 3250a at the tip of the support leg 3104a and a part of the upper surface 3250b at the tip of the support leg 3104b become support regions 3200a and 3200b, respectively. When the support 3004 supports the analysis chip 3002, the support regions 3200a and 3200b are in contact with the supported regions 3110a and 3110b, respectively.

  The support 3004 has a shape that does not contact the prism 3066 when the analysis chip 3002 is supported. This makes it difficult for stress to be applied to the prism 3066, and makes it difficult for birefringence to occur in the prism 3066, improving the sensitivity and accuracy of measurement. The support 3004 has a shape that does not block the excitation light EL and the reflected light RL when the analysis chip 3002 is supported.

  The positioning pins 3300 and 3302 protrude from the support region 3200a and extend perpendicular to the support region 3200a. When the support 3004 supports the analysis chip 3002, the positioning pins 3300 and 3302 are inserted into the positioning holes 3304 and 3306, respectively. The positioning pins 3300 and 3302 restrict the movement of the flow path forming body 3070 in the direction parallel to the joining region 3108, the position of the flow path forming body 3070 is determined, and the prism 3066 is disposed at an appropriate position. The positioning pins 3300 and 3302 may be replaced with other types of positioning structures.

{Fourth embodiment}
The fourth embodiment relates to a support structure that is employed instead of the support structure of the first embodiment.

  The schematic diagrams of FIGS. 17 and 18 show the support structure of the fourth embodiment. 17 is a perspective view, and FIG. 18 is a cross-sectional view. The schematic diagram of FIG. 19 is a perspective view of the analysis chip of the fourth embodiment. The schematic diagram of FIG. 20 is a perspective view of the support body of 4th Embodiment.

  As shown in FIGS. 17 and 18, the support structure 4100 of the fourth embodiment includes an analysis chip 4002, a support body 4004, and a pressing mechanism 4006. The pressing mechanism 4006 of the fourth embodiment is the same as the pressing mechanism 1006 of the first embodiment.

  As shown in FIG. 19, the analysis chip 4002 of the fourth embodiment includes a gold film 4064, a prism 4066, a capturing body 4068, and a flow path forming body 4070. The gold film 4064, the prism 4066, and the capturing body 4068 of the fourth embodiment are the same as the gold film 1064, the prism 1066, and the capturing body 1068 of the first embodiment, respectively. The flow path forming body 4070 of the fourth embodiment is different from that of the first embodiment in that the positions where the supported regions 4110a, 4110b, 4110c and 4110d are set are changed and the positioning holes 4304 and 4306 are formed. Different from the body 1070.

  As shown in FIG. 20, the support body 4004 includes a base 4102, support legs 4104 a, 4104 b, 4104 c and 4104 d, and positioning pins 4300 and 4302. The base 4102 of the fourth embodiment is the same as the base 1102 of the first embodiment. The support 4004 of the fourth embodiment is provided with support legs 4104a, 4104b, 4104c and 4104d instead of the support legs 1104a and 1104b, and further provided with positioning pins 4300 and 4302. Is different.

  The support body 4004 is a four-forked body in which support legs 4104 a, 4104 b, 4104 c and 4104 d having a bar shape branch from the base 4102. The support legs 4104a, 4104b, 4104c, and 4104d extend upward in the vertical direction from the base 4102. A part of the upper surface 4250a at the tip of the support leg 4104a, a part of the upper surface 4250b at the tip of the support leg 4104b, a part of the upper surface 4250c at the tip of the support leg 4104c, and a part of the upper surface 4250d at the tip of the support leg 4104d The parts become support areas 4200a, 4200b, 4200c and 4200d, respectively. When the support 4004 supports the analysis chip 4002, the support areas 4200a, 4200b, 4200c, and 4200d are in contact with the supported areas 4110a, 4110b, 4110c, and 4110d, respectively.

  The support body 4004 has a shape that does not contact the prism 4066 when the analysis chip 4002 is supported. This makes it difficult for stress to be applied to the prism 4066, and makes it difficult for birefringence to occur in the prism 4066, improving the sensitivity and accuracy of measurement. The support 4004 has a shape that does not block the excitation light EL and the reflected light RL when the analysis chip 4002 is supported.

  The positioning pins 4300 and 4302 protrude from the support areas 4200a and 4200b, respectively, and extend perpendicular to the support areas 4200a and 4200b. When the support 4102 supports the analysis chip 4002, the positioning pins 4300 and 4302 are inserted into the positioning holes 4304 and 4306, respectively. Thereby, the position of the flow path forming body 4070 is determined, and the prism 4066 is arranged at an appropriate position.

{Fifth embodiment}
The fifth embodiment relates to a support structure that is employed instead of the support structure of the first embodiment.

  The schematic diagram of FIG.21 and FIG.22 shows the support structure of 5th Embodiment. FIG. 21 is a perspective view, and FIG. 22 is a cross-sectional view. The schematic diagram of FIG. 23 is a perspective view of the analysis chip of the fifth embodiment. The schematic diagram of FIG. 24 is a perspective view of the support body of 5th Embodiment.

  As shown in FIGS. 21 and 22, the support structure 5100 of the fifth embodiment includes an analysis chip 5002, a support 5004, and a pressing mechanism 5006. The analysis chip 5002 and the pressing mechanism 5006 of the third embodiment are the same as the analysis chip 1002 and the pressing mechanism 1006 of the first embodiment.

  As shown in FIG. 23, the analysis chip 5002 of the fifth embodiment includes a gold film 5064, a prism 5066, a capturing body 5068, and a flow path forming body 5070. The gold film 5064, the prism 5066, the capturing body 5068, and the flow path forming body 5070 of the fifth embodiment are the same as the gold film 1064, the prism 1066, the capturing body 1068, and the flow path forming body 1070 of the first embodiment, respectively. is there. The analysis chip 5002 of the fifth embodiment is different from the analysis chip 1002 of the first embodiment in that the regulated regions 5306 and 5308 are set on the surface 5101.

  As shown in FIG. 24, the support body 5004 of the fifth embodiment includes a base 5102 and support legs 5104a and 5104b. The base 5102 of the fifth embodiment is the same as the base 1102 of the first embodiment. The support 5004 of the fifth embodiment is different from the support 1004 of the first embodiment in that positioning grooves 5300 and 5302 are formed.

  The support body 5004 is a bifurcated branch body in which support legs 5104 a and 5104 b having a plate shape branch from the base 5102. Positioning grooves 5300 and 5302 are formed on the upper surface 5250b of the upper surfaces 5250a and 5104b at the distal ends of the support legs 5104a, respectively. When the support body 5004 supports the analysis chip 5002, the flow path forming body 5070 is accommodated in the positioning grooves 5300 and 5302.

  The entire bottom surface of the positioning groove 5300 and the entire bottom surface of the positioning groove 5302 become support regions 5200a and 5200b, respectively. When the support 5004 supports the analysis chip 5002, the support regions 5200a and 5200b are in contact with the supported regions 5110a and 5110b, respectively.

  The support 5004 has a shape that does not contact the prism 5066 when the analysis chip 5002 is supported. This makes it difficult for stress to be applied to the prism 5066, making it difficult for birefringence to occur in the prism 5066, and improving the sensitivity and accuracy of measurement. In addition, the support 5004 has a shape that does not block the excitation light EL and the reflected light RL when the analysis chip 5002 is supported.

  The entire side surface of the positioning groove 5300 and the entire side surface of the positioning groove 5302 become restriction regions 5304 and 5306, respectively. When the support body 5004 supports the analysis chip 5002, the restriction regions 5304 and 5306 are in contact with the restricted regions 5306 and 5308, respectively. The positioning grooves 5300 and 5302 restrict the movement of the flow path forming body 5070 in the direction parallel to the bonding region 5108, the position of the flow path forming body 5070 is determined, and the prism 5066 is disposed at an appropriate position. The positioning grooves 5300 and 5302 restrict the movement of the flow path forming body 5070 in both the direction perpendicular to and parallel to the support legs 5104a and 5104b, but in the direction perpendicular to and parallel to the support legs 5104a and 5104b. It is also permitted to restrict the movement of the flow path forming body 5070 to only one side.

{Sixth embodiment}
The sixth embodiment relates to a support structure that is employed instead of the support structure of the first embodiment.

  The schematic views of FIGS. 25 and 26 show the support structure of the sixth embodiment. 25 is a perspective view, and FIG. 26 is a cross-sectional view. The schematic diagram of FIG. 27 is a perspective view of the analysis chip of the sixth embodiment. The schematic diagram of FIG. 28 is a perspective view of the support body of 6th Embodiment.

  As shown in FIGS. 25 and 26, the support structure 6100 of the sixth embodiment includes an analysis chip 6002, a support 6004, and a pressing mechanism 6006. The pressing mechanism 6006 of the sixth embodiment is the same as the pressing mechanism 1006 of the first embodiment.

  As shown in FIG. 27, the analysis chip 6002 of the sixth embodiment includes a gold film 6064, a prism 6066, a capturing body 6068, and a flow path forming body 6070. The gold film 6064, the prism 6066, and the capturing body 6068 of the sixth embodiment are the same as the gold film 1064, the prism 1066, and the capturing body 1068 of the first embodiment, respectively. In the flow path forming body 6070 of the sixth embodiment, the outer shape is changed from a rectangular parallelepiped to an isosceles trapezoidal column, and the place where the supported regions 6110a and 6110b are set is changed from the lower surface to the inclined side surfaces 6104a and 6104b. This is different from the flow path forming body 1070 of the first embodiment.

  As shown in FIG. 28, the support body 6004 of the sixth embodiment includes a base 6102 and support legs 6104a and 6104b. The base 6102 of the sixth embodiment is the same as the base 1102 of the first embodiment. The support legs 6104a and 6104b of the sixth embodiment are changed so that the outer shape has inclined side surfaces 6250a and 6250b, respectively, and the place where the support regions 6200a and 6200b are set is changed from the upper surface to the inclined side surfaces 6250a and 6250b, respectively. This is different from the support legs 1004a and 1004b of the first embodiment.

  The support body 6004 is a bifurcated branch body in which support legs 6104 a and 6104 b having a plate shape branch from the base 6102. A part of the inclined side surface 6250a of the support leg 6104a and a part of the inclined side surface 6250b of the support leg 6104b become support regions 6200a and 6200b, respectively. The support region 6200a may occupy the entire inclined side surface 6250a, and the support region 6200b may occupy the entire inclined side surface 6250b. When the support 6004 supports the analysis chip 6002, the support regions 6200a and 6200b are in contact with the supported regions 6110a and 6110b, respectively.

  The surface 6101 of the flow path forming body 6070 has flat inclined side surfaces 6104 a and 6104 b and a lower surface 6106. The inclined side surfaces 6104 a and 6104 b are inclined from a direction perpendicular to the lower surface 6106. The interval between one inclined side surface 6104a and the other inclined side surface 6104b becomes narrower as the lower surface 6106 is approached. The supported regions 6110a and 6110b occupy part of the inclined side surfaces 6104a and 6104b, respectively. The supported regions 6110a and 6110b may occupy the entire inclined side surfaces 6104a and 6104b, respectively.

  The support 6004 has a shape that does not contact the prism 6066 when the analysis chip 6002 is supported. This makes it difficult for stress to be applied to the prism 6066, and makes it difficult for birefringence to occur in the prism 6066, improving the sensitivity and accuracy of measurement. In addition, the support 6004 has a shape that does not block the excitation light EL and the reflected light RL when the analysis chip 6002 is supported.

  According to the support structure 6100 of the sixth embodiment, the movement of the flow path forming body 6070 in the direction parallel to the joining region is restricted, the position of the flow path forming body 6070 is determined, and the prism 6066 is disposed at an appropriate position. Is done. This is because the supported regions 6110a and 6110b are set on the inclined side surfaces 6104a and 6104b.

{Seventh embodiment}
The seventh embodiment relates to a support structure that is employed instead of the support structure of the first embodiment.

  The schematic diagrams of FIGS. 29 and 30 show the support structure of the seventh embodiment. 29 is a perspective view, and FIG. 30 is a cross-sectional view. The schematic diagram of FIG. 31 is a perspective view of the analysis chip of 7th Embodiment. The schematic diagram of FIG. 32 is a perspective view of the support body of 7th Embodiment.

  As shown in FIGS. 29 and 30, the support structure 7100 of the seventh embodiment includes an analysis chip 7002, a support 7004, and a pressing mechanism 7006. The pressing mechanism 7006 of the seventh embodiment is the same as the pressing mechanism 1006 of the first embodiment.

  As shown in FIG. 31, the analysis chip 7002 of the seventh embodiment includes a gold film 7064, a prism 7066, a capturing body 7068, and a flow path forming body 7070. The gold film 7064, the prism 7066, and the capturing body 7068 of the seventh embodiment are the same as the gold film 1064, the prism 1066, and the capturing body 1068 of the first embodiment, respectively. In the flow path forming body 7070 of the seventh embodiment, the outer shape is changed from a rectangular parallelepiped to an isosceles trapezoidal column, and the place where the supported regions 7110a, 7110b, 7110c and 7110d are set is changed from the lower surface to the inclined side surfaces 7104a and 7104b. It differs from the flow path forming body 1070 of the first embodiment in that it is changed.

  As shown in FIG. 32, the support body 7004 of the seventh embodiment includes a base 7102 and support legs 7104a, 7104b, 7104c, and 7104b. The base 7102 of the seventh embodiment is the same as the base 1102 of the first embodiment. The support 7002 of the seventh embodiment is changed to support legs 7104a, 7104b, 7104c and 7104d in which the support legs 1104a and 1104b have inclined side surfaces 7250a, 7250b, 7250c and 7250d, and the support regions 7200a, 7200b, 7200c and 7200d are changed. It differs from the flow path forming body 1070 of the first embodiment in that the place to be set is changed from the upper surface to the inclined side surfaces 7250a, 7250b, 7250c and 7250d.

  The support body 7004 is a four-forked body in which support legs 7104 a, 7104 b, 7104 c, and 7104 d having a bar shape are branched from the base 7102. A part of the inclined side surface 7250a of the support leg 7104a, a part of the inclined side surface 7250b of the support leg 7104b, a part of the inclined side surface 7250c of the support leg 7104c, and a part of the inclined side surface 7250d of the support leg 7104d are respectively supported regions 7200a. 7200b, 7200c, and 7200d. The support regions 7200a, 7200b, 7200c, and 7200d may occupy the entire inclined side surfaces 7250a, 7250b, 7250c, and 7250d, respectively. When the support 7004 supports the analysis chip 7002, the support regions 7200a, 7200b, 7200c, and 7200d are in contact with the supported regions 7110a, 7110b, 7110c, and 7110d, respectively.

  The surface 7101 of the flow path forming body 7070 has flat inclined side surfaces 7104 a and 7104 b and a lower surface 7106. The inclined side surfaces 7104 a and 7104 b are inclined from a direction perpendicular to the lower surface 7106. The distance between one inclined side surface 7104a and the other inclined side surface 7104b becomes narrower as the lower surface 7106 is approached. The supported regions 7110a and 7110b occupy a part of the inclined side surface 7104a, and the supported regions 7110c and 7110d occupy a part of the inclined side surface 7104b.

  The support 7004 has a shape that does not contact the prism 7066 when the analysis chip 7002 is supported. This makes it difficult for stress to be applied to the prism 7066 and makes it difficult for birefringence to occur in the prism 7066, improving the sensitivity and accuracy of measurement. The support 7004 has a shape that does not block the excitation light EL and the reflected light RL when the analysis chip 7002 is supported.

  According to the support structure 7100 of the seventh embodiment, the movement of the flow path forming body 7070 in the direction parallel to the joining region is restricted, the position of the flow path forming body 7070 is determined, and the prism 7066 is disposed at an appropriate position. Is done. This is because the supported regions 7110a, 7110b, 7110c, and 7110d are set on the inclined side surfaces 7104a and 7104b.

  Although the present invention has been described in detail, the above description is illustrative in all aspects, and the present invention is not limited to the above description. Innumerable modifications not illustrated can be envisaged without departing from the scope of the present invention.

1000 Measuring device 1004, 2004, 3004, 4004, 5004, 6004, 7004 Support 1066, 2066, 3066, 4066, 5066, 6066, 7066 Prism 1064, 2064, 3064, 4064, 5064, 6064, 7064 Gold film 1070, 2070 , 3070, 4070, 5070, 6070, 7070 flow path forming body

Claims (7)

A support structure in a measurement device that performs measurement by surface plasmon excitation fluorescence spectroscopy,
A structure having a first surface, wherein the first surface has a bonding region and a supported region, a sample storage space is formed, and the sample storage space has an opening in the bonding region;
The second surface has an incident area, a reflection area, and an emission area, and the excitation light incident on the incident area is totally reflected by the reflection area and emitted from the emission area. A dielectric medium in which the incident region, the reflective region, and the emitting region are disposed;
A conductor film having a first main surface and a second main surface, wherein the first main surface is bonded to the bonding region, and the second main surface is in close contact with the reflection region;
A support body that contacts the supported area, and a support body that has a shape that separates from the dielectric medium when the support area contacts the supported area; and
A support structure comprising: The support structure of claim 1,
A support structure in which the first surface has a flat surface, and the supported region and the bonding region are provided on the flat surface. The support structure of claim 2,
A support structure having a positioning structure in which the support body restricts movement of the structure in a direction parallel to the joining region. The support structure according to claim 3, wherein
The positioning structure is
A positioning pin protruding from the support region and extending perpendicular to the support region;
A support structure in which a positioning hole into which the positioning pin is inserted is formed in the structure when the support region is in contact with the supported region. The support structure according to claim 3, wherein
A support structure in which the positioning structure is a positioning groove for accommodating the structure. The support structure of claim 1,
The first surface has a first flat surface, a second flat surface, and a third flat surface;
The second flat surface and the third flat surface are inclined from a direction perpendicular to the first flat surface, and a distance between the second flat surface and the third flat surface is the first flat surface. It gets narrower as you get closer to the surface,
The supported region is a first supported region, the first surface has a second supported region;
The joining region is on the first flat surface;
The first supported region is on the second flat surface;
The second supported region is on the third flat surface;
A support structure having a second support region in which the support region is a first support region and the support is in contact with the second supported region. A measurement device that performs measurement by surface plasmon excitation fluorescence spectroscopy,
A structure having a first surface, wherein the first surface has a bonding region and a supported region, a sample storage space is formed, and the sample storage space has an opening in the bonding region;
The second surface has an incident area, a reflection area, and an emission area, and the excitation light incident on the incident area is totally reflected by the reflection area and emitted from the emission area. A dielectric medium in which the incident region, the reflective region, and the emitting region are disposed;
A conductor film having a first main surface and a second main surface, wherein the first main surface is bonded to the bonding region, and the second main surface is in close contact with the reflection region;
A support body that contacts the supported area, and a support body that has a shape that separates from the dielectric medium when the support area contacts the supported area; and
A measurement mechanism for making excitation light incident on the incident surface and performing measurement by surface plasmon excitation fluorescence spectroscopy;
A measuring device comprising:

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