JP2007071548A - Prism/liquid reservoir integrated type chip for measuring surface plasmon resonance spectrum, its manufacturing method and surface plasmon resonance measuring instrument using prism/liquid reservoir integrated type chip - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a prism/liquid reservoir integrated type chip dispensing with the highly precise positioning with respect to a surface plasmon resonance measuring instrument and the surface plasmon resonance measuring instrument using the chip. <P>SOLUTION: The prism/liquid reservoir integrated type chip is equipped with a flange 10 having a seat 12, the liquid reservoir part 4 having a cup structure formed in the bottom part of the liquid reservoir part having the cup structure, the metal thin film 9 formed in the bottom part of the liquid reservoir part having the cup structure and the semispherical prism 5 formed in the seat. The surface plasmon resonance measuring instrument is equipped with the detachable prism/liquid reservoir integrated type chip, the holder 15 for holding the chip and having an opening part larger than the diameter of the semispherical prism and a foot longer than the radius of the semispherical prism and an optical system constituted of a light source, a mirror 2a for reflecting the light from the light source to input the reflected light to the semispherical prism, a polarizer 6 for transmitting the light reflected from the plane of the semispherical prism to output the same and a mirror 2b fore reflecting the light transmitted through the polarizer to input the same to an analyzing part 3. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to surface plasmon resonance measurement, and more particularly to a prism / liquid reservoir integrated chip for surface plasmon resonance spectrum measurement, a manufacturing method thereof, and a surface plasmon resonance measurement apparatus using the same.

  In surface plasmon resonance measurement, light is incident on a prism on which gold, silver, or the same thin film is formed so as to satisfy the total reflection condition, the angle spectrum of the reflected light is obtained, and the absorption peak appearing in the spectrum is applied to the metal thin film. This is a technique for measuring the refractive index of a substance in contact with it or its change.

  For example, if a substance that causes a molecule-specific reaction, such as an ionophore, an antibody, an enzyme, or a molecularly imprinted polymer, is immobilized on a metal thin film, it is selective between the object to be measured and the substance having a fixed molecular specificity. Since the reaction causes a change in refractive index, the concentration of ions, antigens, enzyme substrates, or other substances can be measured using a surface plasmon resonance sensor.

  A conventional surface plasmon resonance measurement device uses a prism that is expensive and accurately polished, and the prism is fixed on a stationary or operable table, and a light source and a detector such as a camera are properly arranged. Have In order to provide a sensing function, it is necessary to form a substance having molecular specificity on a metal thin film, but if it is directly modified on a prism, inexpensive measurement cannot be performed. Therefore, a method is generally employed in which a substrate made of the same material as the prism is prepared, a metal thin film and a modification layer are formed on the substrate, and the substrate is bonded to the prism via an oil or film. On the other hand, since the thickness of the adhesive layer and the degree of adhesion due to this oil and film affect the surface plasmon resonance spectrum, it is necessary to accurately control the oil and film thickness when mounting the substrate on the prism during measurement. It is.

  On the other hand, a chip (hereinafter also referred to as a prism / liquid reservoir integrated chip) integrated with a prism and a cup-structured liquid holding portion that enables liquid storage on the prism, and a surface plasmon resonance measuring apparatus using the chip Has been proposed (see, for example, Non-Patent Reference 1). Since this prism / liquid reservoir integrated chip is a disposable part and the prism itself is also replaced at the same time, the measurement error due to the adhesive layer between the prism and the substrate, which has been a problem in the past, is eliminated. The previously proposed prism / reservoir integrated chip has a shape in which the apex of a square pyramid is cut off, and light is incident / exited on the flat portion of the quadrangular pyramid.

JP 2004-117955 A Masayuki Naya, 4 others, “High-sensitivity SPR sensor”, Optical Design Research Group 31st Research Group, Japan Society of Applied Physics, Japan Optical Society, December 2004, p. 21-25

  However, the conventional surface plasmon resonance measuring device using the prism / liquid reservoir integrated chip is replaced with the surface plasmon resonance measuring apparatus every time the measurement is performed, so that the light incident surface is flat. There is a problem that the optical path of the incident light is deviated from the normal line of the plane, and the reflection component and the scattering component of the incident light are increased. In addition, there is a problem that a measurement error occurs between the replaced prism / liquid reservoir integrated chip.

  The present invention has been made in view of such a problem, and its object is to provide a prism / liquid reservoir integrated chip that does not require high-precision positioning when it is replaced with a surface plasmon resonance measuring apparatus. It is to provide. Another object is to provide an inexpensive prism / liquid reservoir integrated chip.

  In order to achieve the above object, the invention according to claim 1 is a prism / reservoir-integrated chip provided on a flange facing a seat and a surface facing the seat. And a metal thin film formed on the bottom of the liquid reservoir, and a hemispherical prism formed on the seat.

  The invention described in claim 2 is characterized in that the liquid reservoir according to claim 1 has a cup structure.

  According to a third aspect of the present invention, the liquid reservoir according to the first aspect has a flow cell structure including an inlet and an outlet.

  The invention according to claim 4 is the resin whose main component is the hemispherical prism according to claim 1, 2, or 3, comprising 1,4-cyclohexanedimethanol divinyl ether and vinylcyclohexanedioxide. The refractive index is 1.46 to 1.67.

  According to a fifth aspect of the present invention, the hemispherical prism according to the first, second, or third aspect is an acrylic resin mainly composed of maleic anhydride, propylene glycol, and methacrylate, and has a refractive index of 1. .46 to 1.67.

  The invention according to claim 6 is a surface plasmon resonance measuring device, which is detachable from the prism / liquid reservoir integrated chip according to any one of claims 1 to 5 and the diameter of the hemispherical prism. The light source includes a holder having a large opening smaller than the diameter of the flange, housing the hemispherical prism in the opening and holding the prism / liquid reservoir integrated chip, a light source, and a light detecting unit. And an optical system adjusted so as to be totally reflected at the interface between the flange and the metal thin film.

  The invention according to claim 7 is a method of manufacturing a prism / liquid reservoir integrated chip, wherein a flange having a counterbore and a liquid reservoir part of a cup structure provided on a surface of the flange facing the counterbore A step of dripping a resin onto the seat using a dispenser or an inkjet, a step of curing the dripped resin, and a step of forming a metal thin film on the bottom of the liquid reservoir of the cup structure, It is characterized by including.

  The invention according to claim 8 is a method of manufacturing a prism / liquid reservoir integrated chip, the step of producing a flange having a seat face, and the step of dripping a resin onto the seat face using a dispenser or an inkjet. A step of curing the dripped resin, a step of forming a metal thin film on the bottom of the reservoir of the cup structure, and a reservoir of the flow cell structure provided on the surface of the flange facing the seating And a manufacturing step.

  In the invention according to claim 9, the resin according to claim 7 or 8 is mainly composed of 1,4-cyclohexanedimethanol divinyl ether and vinylcyclohexanedioxide, and the composition of the resin has a refractive index after curing. Is adjusted to be 1.46 to 1.67.

  According to a tenth aspect of the present invention, the resin according to the seventh or eighth aspect is an acrylic resin mainly composed of maleic anhydride, propylene glycol, and methacrylate, and the composition of the resin is a refractive index after curing. The ratio is adjusted to be 1.46 to 1.67.

  As described above, according to the present invention, it is possible to provide a prism / liquid reservoir integrated chip that does not require high-precision positioning when the surface plasmon resonance measuring apparatus is replaced. In addition, an inexpensive prism / liquid reservoir integrated chip can be provided.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the drawings described below, components having the same function are denoted by the same reference numerals, and repeated description thereof is omitted.

  A prism / reservoir integrated chip according to the present invention includes a flange having a seat face, a liquid reservoir portion provided on a surface facing the seat face, a metal thin film formed on a bottom portion of the liquid reservoir portion, a seat And a hemispherical prism formed in a bow.

  Further, the surface plasmon resonance measuring apparatus using the prism / liquid reservoir integrated chip according to the present invention includes a detachable prism / liquid reservoir integrated chip, and a hemisphere holding the prism / liquid reservoir integrated chip. A holder with an opening larger than the diameter of the prism and a leg longer than the radius of the hemispherical prism, a light source, a mirror that reflects light from the light source, and enters the hemispherical prism, and is reflected by the hemispherical prism plane A polarizer that transmits the output light, and an optical system that includes a mirror that reflects the light transmitted through the polarizer and inputs the light to the light detection unit.

[First Embodiment]
With reference to FIG. 3, a first embodiment of the prism / liquid reservoir integrated chip according to the present invention will be described. 3A, 3B, and 3C are a top view, a vertical sectional view, and a bottom view, respectively, of the prism / liquid reservoir integrated chip of this embodiment.

  The prism / reservoir integrated chip is formed at a flange 10 having a counterbore 12, a cup structure liquid reservoir 4 provided on the surface of the flange facing the counterbore, and a bottom of the cup structure liquid reservoir. A metal thin film 9 and a hemispherical prism 5 formed on the face.

  The flange 10 is provided with notches 11a, 11b, and 11c so that the prism / liquid reservoir integrated chip can be stably placed on the holder of the surface plasmon resonance measuring apparatus described below.

  The flange 10 also has a function of preventing contamination of the hemispherical prism by the solution, which may occur when a solution or the like is poured into the liquid reservoir 4 having a cup structure.

  When surface plasmon resonance measurement is performed using a prism / liquid reservoir integrated chip, a modification layer is formed so as to adhere to the metal thin film 9, and ions, antigens, and enzyme substrates are formed in the liquid reservoir portion 4 of the cup structure. A solution containing a substance such as is injected.

  The metal thin film 9 is a thin film such as gold, silver, or copper, and is formed by a vapor deposition method, a sputtering method, or a wet method. The thickness of the metal thin film is produced with an optimum thickness obtained from optical calculation.

  The hemispherical prism 5 is made of plastic that is inexpensive and suitable for disposable use. A method for manufacturing the plastic semispherical prism will be described below.

  In this embodiment, the flange 10 has three notches (11a, 11b, 11a, 11b, so that the prism / liquid reservoir integrated chip can be easily installed in the holder of the surface plasmon resonance measuring apparatus described below. 11c) Although the example of being provided is shown, the number of notches is not limited to this, or an orientation flat may be provided instead of the notches as shown in FIG.

(Production method of prism / liquid reservoir integrated chip of this embodiment)
With reference to FIG. 2, the manufacturing method of the prism / liquid reservoir integrated chip of this embodiment will be described.
(1) First, using a mold, the flange 10 having the counterbore 12 and the liquid reservoir 4 having a cup structure provided on the surface facing the counterbore are produced.
(2) Next, a resin (polymer solution) that is a material of the hemispherical prism 5 is filled in a dispenser and dropped onto a seat.
(3) The resin dropped on the seat is cured.
(4) Next, a metal thin film is formed.

  The material of the flange 10 and the liquid reservoir 4 having a cup structure is a post-curing refraction mainly composed of a vinyl ether resin (1,4-cyclohexanedimethanol divinyl ether) and an alicyclic epoxy resin (vinyl cyclohexane dioxide). A resin having a rate of 1.513 can be used.

  The material of the semispherical prism 5 is preferably a material that is transparent to the wavelength used and has a low curing shrinkage rate. For example, it is appropriate to use an epoxy resin or an acrylic resin. In particular, an epoxy resin is suitable for curing by ring-opening polymerization, so that no by-product is produced and the curing shrinkage is as small as 1 to 5%. Based on bisphenol A based epoxy resin, the viscosity should be suitable for molding by mixing reactive cyclohexane vinylcyclohexane, 3,4-epoxycyclohexylmethyl-3,4 epoxycyclohexanecarboxylate, etc. Can do. Since these resin materials do not contain a solvent and are 100% composed of a curing component, there is little shape change after curing, and a smooth surface can be obtained. In the present embodiment used as a prism, the surface roughness greatly affects the light condensing characteristics of the prism, and thus using these resin materials is a particularly great advantage.

  Usually, these resin materials are often used by thermosetting with a curing agent such as polyamine, but can be easily UV-cured by adding an appropriate photopolymerization initiator. Moreover, a refractive index can be adjusted by containing a fluorine atom or a sulfur atom. By mixing the fluorine atom content from 0 to 30%, the refractive index can be lowered to about 1.46, and conversely, by mixing sulfur atoms, the refractive index can be raised to about 1.67. it can. Since the refractive index is proportional to their atomic content, it can be accurately adjusted with a refractive index accuracy of 0.01 or less.

  It is necessary to prepare the material so that the refractive index of the hemispherical prism becomes an optimum value calculated from the wavelength of light used for the surface plasmon resonance measurement and the configuration of the optical system.

  Examples of the epoxy resin used for the material of the hemispherical prism 5 include a vinyl ether resin (1,4-cyclohexanedimethanol divinyl ether), an alicyclic epoxy resin (vinyl cyclohexane dioxide), and a sulfonium salt photopolymerization initiator. UV curable resin (viscosity is about 6 cps). Since the dispenser can also discharge a high viscosity material, the bisphenol A-based resin can be dropped as it is.

  In addition, a resin that is a material of a hemispherical prism can be dropped on a seat using an inkjet instead of a dispenser (see, for example, Patent Reference 1). When an ink jet is used when producing a semispherical prism, the resin viscosity that can be ejected is low. Therefore, in addition to the low viscosity resin using the reactive diluent, a vinyl ether resin (1, 4 It is also effective to use (cyclohexanedimethanol divinyl ether).

  The resin used for the material of the hemispherical prism 5 can be an acrylic resin mainly composed of maleic anhydride, propylene glycol and methacrylate instead of the epoxy resin. Similarly to the above, the refractive index can be accurately adjusted with a refractive index accuracy of 0.01 or less in the range of 1.46 to 1.67.

  As described above, thermosetting ultraviolet curing can be performed by adding an additive to the material composition of the hemispherical prism.

  A prism / liquid reservoir integrated chip manufactured according to the above (1) to (4) will be exemplified. The liquid storage part 4 of the manufactured prism / liquid storage integrated chip has a cup structure that has a circular bottom and can hold a solution of about 300 μL with a depth of about 8 mm. The flange 10 has a diameter of 7 mm, and has a circular counterbore 12 corresponding to the thickness of the flange at the center of the bottom.

  For the material of the hemispherical prism, an ultraviolet curable resin comprising a vinyl ether resin (1,4-cyclohexanedimethanol divinyl ether), an alicyclic epoxy resin (vinyl cyclohexane dioxide), and a sulfonium salt photopolymerization initiator is used. This was filled in a dispenser, and 2.25 μL was dropped from the nozzle onto the center part of the flange seat.

Furthermore, when the UV curable resin dropped was irradiated with 100 mW cm ⁻² of UV light and cured, a prism / liquid having a hemispherical prism (refractive index after curing of 1.513) with a diameter of 3 mm at the seating portion of the flange 10. A reservoir-integrated chip could be produced.

  It was confirmed that a good spherical surface having a surface roughness of 0.1 μm or less and a shape accuracy of 1 μm or less was formed for the prepared semicircular prism of the prism / liquid reservoir integrated chip.

  In addition, by making the shape of the seating provided on the flange circular, the resin dropped on the center part of the seating naturally forms a hemisphere at the center of the flange, and the eccentricity of the hemispherical prism is reduced. It becomes easy to keep it small. Thereby, the dispersion | variation in the condensing position of the input light becomes small, and even a very small amount of sample can be measured efficiently.

[Second Embodiment]
Next, referring to FIG. 4, a second embodiment of the prism / liquid reservoir integrated chip according to the present invention will be described. 4A, 4B, and 4C are a top view, a vertical cross-sectional view, and a bottom view, respectively, of the prism / liquid reservoir integrated chip of this embodiment.

  The prism / reservoir-integrated chip is formed at the flange 10 having the counterbore 12, the flow cell structure liquid reservoir 16 provided on the surface of the flange facing the counterbore, and the bottom of the flow cell structure liquid reservoir. A metal thin film 9 and a hemispherical prism 5 formed on the face.

  The liquid reservoir 16 of the flow cell structure forms a cavity 13 on the surface of the flange, and the metal thin film 9 is formed in the cavity. The liquid reservoir 16 having the flow cell structure is provided with inlets / outlets 14 a and 14 b connected to the cavity 13. A liquid feed pump or syringe is connected to one of the inlets / outlets 14a and 14b via a tube, and a solution containing substances such as ions, antigens, and enzyme substrates is continuously sent to the cavity 13, and the solution is replaced. Can do.

  The flange 10 is provided with notches 11a, 11b, and 11c so that the prism / liquid reservoir integrated chip can be stably placed on the holder of the surface plasmon resonance measuring apparatus described below.

(Production method of prism / liquid reservoir integrated chip of this embodiment)
With reference to FIG. 5, a method for manufacturing the prism / liquid reservoir integrated chip of this embodiment will be described.
(1) First, the flange 10 having the counterbore 12 is produced using a mold.
(2) Next, a resin (polymer solution) that is a material of the hemispherical prism 5 is filled in a dispenser and dropped onto a seat.
(3) The resin dropped on the seat is cured.
(4) Next, a metal thin film is formed.
(5) Next, the liquid reservoir 16 having the flow cell structure is coupled to the flange 10.

  The liquid reservoir 16 having a flow cell structure can be made of a polymer material such as polydimethylsiloxane or acrylic.

[Third Embodiment]
With reference to FIGS. 1 and 6, an embodiment of a surface plasmon resonance measuring apparatus using a prism / liquid reservoir integrated chip according to the present invention will be described. FIGS. 1A and 1B are a top view and a vertical sectional view, respectively, of the surface plasmon resonance measuring apparatus of the present embodiment. The surface plasmon resonance measuring apparatus of this embodiment is a surface plasmon resonance measuring apparatus using the prism / liquid reservoir integrated chip (FIG. 3) described in the first embodiment.

  The surface plasmon resonance measuring apparatus using the prism / liquid reservoir integrated chip of this embodiment includes a detachable prism / liquid reservoir integrated chip, and a hemispherical prism 5 that holds the prism / liquid reservoir integrated chip. A holder 15 having an opening larger than the diameter and smaller than the diameter of the flange 10 and a leg longer than the radius of the hemispherical prism, a light source 1, and a mirror 2a that reflects light from the light source and inputs it to the hemispherical prism. A polarizer 6 that is input to the hemispherical prism and is reflected by the interface between the flange and the metal thin film (also referred to herein as a semispherical prism plane) and transmits light output from the hemispherical prism; And an optical system including a mirror 2b that reflects the light transmitted through the polarizer and inputs the light to the light detection unit 3. A personal computer (PC) is connected to the light detector 3.

  FIGS. 6A and 6B are views showing a part of FIG. 1B and a view of the holder 15 from below. The holder 15 accommodates a hemispherical prism in the opening, and holds the prism / liquid reservoir integrated chip vertically. Further, the holder 15 is provided with convex portions 8a, 8b, and 8c that fit into the notches on the flange 10 of the prism / liquid reservoir integrated chip.

  The optical system is adjusted so that light from the light source 1 enters the hemispherical prism 5 and total reflection of light occurs at the interface between the flange 10 and the metal thin film 9.

  In the prism / liquid reservoir integrated chip according to the present invention, the light 7 from the light source 1 halves the half-sphere with respect to the half-sphere prism 5 (the range indicated by the arrow A in FIG. 6A). Regardless of where it is illuminated, the light will always be coupled to the center point. Therefore, the increase in scattered light and reflected light does not occur due to the deviation of the optical axis that may occur when the prism / liquid reservoir integrated chip is replaced. This means that the light is always coupled to the center point of the prism plane of the prism / liquid reservoir integrated chip. As a result, the light utilization efficiency is improved, and the sensitivity in the surface plasmon resonance measurement can be improved.

  In another embodiment of the surface plasmon resonance measuring apparatus using the prism / liquid reservoir integrated chip, a prism / liquid reservoir integrated chip in which an orientation flat is provided on the flange 10 shown in FIG. 7 can be used. In this case, as shown in FIG. 8A, the holder 15 is provided with a rectangular strip that contacts the orientation flat of the flange 10 of the prism / liquid reservoir integrated chip. 7A, 7B, and 7C are a top view, a vertical sectional view, and a bottom view, respectively, of a prism / liquid reservoir integrated chip in which an orientation flat is provided on the flange 10. FIG. It is. FIGS. 8A and 8B are a top view and a vertical cross-sectional view, respectively, of a surface plasmon resonance measuring apparatus using a prism / liquid reservoir integrated chip in which an orientation flat is provided on the flange 10. .

(Operation of surface plasmon resonance measuring device)
Next, the operation of the surface plasmon resonance measuring apparatus will be described with reference to FIG. The light 7 output from the light source 1 is reflected by the mirror 2a, enters the hemispherical prism 5, and is reflected by the hemispherical prism plane. The light output from the hemispherical prism passes through the polarizer 6, is reflected by the mirror 2b, and is input to the light detector 3 and received.

  Data relating to the light received by the light detection unit 3 such as a camera is transmitted to the PC and is subjected to data processing for calibration to obtain an SPR signal.

(SPR data)
FIG. 9 shows a surface plasmon resonance spectrum obtained by injecting water into the liquid reservoir 4 of the cup structure of the prism / liquid reservoir integrated chip using the surface plasmon resonance measuring apparatus of this embodiment.

  For example, when the light detection unit 3 is mounted with a camera using a plurality of light receiving elements such as CCD elements, each data obtained by the PC corresponds to the light intensity in each light receiving element. By obtaining the relationship between the light receiving element of the camera and the angle of light incident on the interface between the flange and the metal thin film in advance, the surface whose vertical axis is the light intensity and whose horizontal axis is the angle as shown in FIG. A plasmon resonance spectrum can be obtained.

(A) is the figure which looked at the surface plasmon resonance measuring apparatus of embodiment of this invention from the top, (b) is sectional drawing of a perpendicular direction. It is a figure for demonstrating the manufacturing method of the prism and the liquid reservoir integrated chip | tip of embodiment of this invention. (A) is the figure which looked at the prism / liquid reservoir integrated chip | tip of embodiment of this invention from the top, (b) is sectional drawing of a perpendicular direction, (c) is the figure seen from the bottom. (A) is the figure which looked at the prism / liquid reservoir integrated chip | tip of embodiment of this invention from the top, (b) is sectional drawing of a perpendicular direction, (c) is the figure seen from the bottom. It is a figure for demonstrating the manufacturing method of the prism and the liquid reservoir integrated chip | tip of embodiment of this invention. (A) is a figure which shows a part of FIG.1 (b), (b) is the figure which looked at the holder of FIG.1 (b) from the bottom. (A) is the figure which looked at the prism / liquid reservoir integrated chip | tip which provided the orientation flat in the flange of embodiment of this invention from the top, (b) is sectional drawing of a perpendicular direction, (c) is the figure seen from the bottom. is there. (A) is the figure which looked at the surface plasmon resonance measuring apparatus using the prism and liquid reservoir integrated type chip which provided flange 10 orientation flat of an embodiment of the present invention from the top, and (b) is a sectional view of the perpendicular direction. It is the surface plasmon resonance spectrum obtained using the surface plasmon resonance measuring apparatus of embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Light source 2a, 2b Mirror 3 Analyzing part 4 Liquid reservoir part of cup structure 5 Semispherical prism 6 Polarizer 7 Light 8, 8a, 8b, 8c Convex part 9 Metal thin film 10 Flange 11a, 11b, 11c Notch 12 Seat Swell 13 Cavity 14a, 14b Inlet / Outlet 15 Holder 16 Liquid cell reservoir

Claims (10)

A flange with a seat;
A liquid reservoir provided on the surface facing the seat;
A metal thin film formed on the bottom of the liquid reservoir,
A prism / liquid reservoir integrated chip comprising: a hemispherical prism formed on a sitting surface.   The prism / liquid reservoir integrated chip according to claim 1, wherein the liquid reservoir has a cup structure.   The prism / reservoir integrated chip according to claim 1, wherein the liquid reservoir has a flow cell structure including an inlet and an outlet.   The hemispherical prism is a resin mainly composed of 1,4-cyclohexanedimethanol divinyl ether and vinylcyclohexanedioxide, and has a refractive index of 1.46 to 1.67. The prism / liquid reservoir integrated type chip according to 1, 2, or 3.   The hemispherical prism is an acrylic resin mainly composed of maleic anhydride, propylene glycol, and methacrylate, and has a refractive index of 1.46 to 1.67. Alternatively, the prism / liquid reservoir integrated chip according to 3. A prism / liquid reservoir integrated chip according to any one of claims 1 to 5, which is detachable,
A holder that has an opening that is larger than the diameter of the hemispherical prism and smaller than the diameter of the flange, and that holds the hemispherical prism in the opening and holds the prism / liquid reservoir integrated chip;
An optical system that includes a light source and an analyzer, and is adjusted so that light from the light source is input to the hemispherical prism and totally reflected at an interface between the flange and the metal thin film. Surface plasmon resonance measuring device. Producing a flange having a countersink, and a liquid reservoir of a cup structure provided on a surface of the flange facing the countersink;
Dropping a resin on the seat using a dispenser or an inkjet; curing the dropped resin;
Forming a metal thin film on the bottom of the liquid reservoir of the cup structure. A method for manufacturing a prism / liquid reservoir integrated chip. Creating a flange with a seat;
Dropping a resin on the seat using a dispenser or an inkjet; curing the dropped resin;
Forming a metal thin film on the bottom of the liquid reservoir of the cup structure;
And a step of producing a flow reservoir structured liquid reservoir provided on a surface of the flange facing the seating. A method for manufacturing a prism / liquid reservoir integrated chip.   The resin is mainly composed of 1,4-cyclohexanedimethanol divinyl ether and vinylcyclohexanedioxide, and the composition of the resin is prepared so that the refractive index after curing is 1.46 to 1.67. 9. The method for manufacturing a prism / liquid reservoir integrated chip according to claim 7 or 8, wherein: The resin is an acrylic resin mainly composed of maleic anhydride, propylene glycol and methacrylate, and the composition of the resin is adjusted so that the refractive index after curing is 1.46 to 1.67. The method for producing a prism / liquid reservoir integrated chip according to claim 7 or 8, wherein

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