Patent Publication Number: US-2013242298-A1

Title: Prism part of analysis chip, analysis chip including the prism part, and method for producing prism part of analysis chip

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This is the U.S. national stage of application No. PCT/JP2011/005126, filed on 12 Sep. 2011. Priority under 35 U.S.C. §119(a) and 35 U.S.C. §365(b) is claimed from Japanese Application No. 2010-263856, filed 26 Nov. 2010, the disclosure of which is also incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present invention relates to a prism part of an analysis chip for use in a surface plasmon resonance analysis device for analyzing a specimen based on a change in the resonance angle of surface plasmon resonance (SPR), or for use in a surface plasmon resonance fluorescence analysis device for analyzing a specimen by causing the specimen or a fluorescent material labeled to the specimen to emit fluorescence with use of an evanescent wave generated by surface plasmon resonance, and by measuring the fluorescence, as well as an analysis chip including the prism part, and a method for producing the prism part of the analysis chip. 
     BACKGROUND ART 
     Conventionally, there have been developed various analysis methods utilizing surface plasmon resonance, as a method for quantitatively analyzing a trace amount of a specimen contained in a sample solution for use in biomeasurement for detecting proteins or DNAs. In most of these analysis methods, an analysis chip using a Kretschmann configuration, in which a gold film is formed on a prism, is used. A change in the resonance angle of surface plasmon resonance, or an enhanced electric field in the vicinity of a gold film based on surface plasmon resonance in the analysis chip is utilized, and analysis of a trace amount of a specimen contained in a sample solution is carried out with high sensitivity and with high precision (see patent literature 1). 
     Specifically, as shown in  FIG. 12 , an analysis chip is provided with a prism part  111 , and a channel member  117  which is cooperative with the prism part  111  to form channel  116  for flowing a sample solution. The prism part  111  has a prism main body  112  made of glass or a resin, and a gold film  113  formed on a predetermined surface  112   b  of the prism main body  112 . 
     Incidence of excitation light into the prism main body  112  of the analysis chip  110  causes reflection of the excitation light on the gold film  113  formed on the predetermined surface  112   b.  Then, an electric filed near the surface of the gold film  113  is greatly enhanced by the excitation light incident at a predetermined incident angle. This is because incidence of excitation light into the gold film  113  at a predetermined incident angle (resonance angle) generates surface plasmon resonance on the gold film  113 , whereby the electric filed near the surface of the gold film  113  is greatly enhanced. This phenomenon is highly sensitive and responsive to a change in the refractive index on the surface of the gold film  113 . Thus, utilizing the above phenomenon enables to detect a trace amount of a material residing in a sample solution flowing over the gold film  113 . 
     However, due to weak adhesion of the gold film  113  to glass or to a resin and softness of the gold film  113 , the gold film  113  is easily peeled off from the prism main body  112  or easily damaged. As a result, a part of the gold film  113  may be peeled off from the prism main body  112  or may be damaged in assembling into an analysis chip  110 , or in washing the channel  116  of the analysis chip  110  each time a specimen is analyzed. 
     Specifically, peeling off or damage may be generated in the gold film  113 , in the case where a portion of the prism part  111  at which the gold film  113  is formed is nipped with, e.g., a pair of tweezers for joining the prism part  111  and the channel member  117 , after the gold film  113  is formed on the predetermined surface  112   b  of the prism main body  112 . Further, in the case where the prism part  111  and the channel member  117  are temporarily detached from each other for washing, e.g., the channel  116 , the gold film  113  may be peeled off from the prism main body  112  or may be damaged at a portion in contact with the channel member  117 . As described above, in the case where peeling off or damage is generated in the gold film  113 , detection of a specimen may not be carried out with precision in analyzing the specimen with use of the analysis chip  110  incorporated with the prism part  111 . 
     CITATION LIST 
     Patent Literature 
     Patent literature 1: Japanese Patent No. 4,370,383 
     SUMMARY OF INVENTION 
     An object of the invention is to provide a prism part of an analysis chip in which peeling off of a gold film is suppressed, an analysis chip including the prism part, and a method for producing the prism part of the analysis chip. 
     A prism part of an analysis chip, an analysis chip including the prism part, and a method for producing the prism part of the analysis chip of the invention have a feature that a prism main body has a mixed layer in which gold and a material constituting the prism main body coexist along a specified surface on which a gold film is formed and on an inner side of the specified surface. The invention having the above configuration provides a prism part of an analysis chip in which peeling off of a gold film is suppressed, an analysis chip including the prism part, and a method for producing the prism part of the analysis chip. 
     These and other objects, features and advantages of the present invention will become more apparent upon reading the following detailed description along with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  is a perspective view of an analysis chip embodying the invention; 
         FIG. 2  is an end view taken along the line II-II in  FIG. 1 ; 
         FIG. 3  is an exploded perspective view of the analysis chip; 
         FIG. 4  is a cross-sectional view illustrating a structure of a prism part of an analysis chip as a modification; 
         FIG. 5  is an enlarged sectional view illustrating a mixed layer portion; 
         FIG. 6  is an exploded perspective view of an analysis chip, illustrating a seal member in a modification; 
         FIG. 7  is a flowchart of a method for producing an analysis chip embodying the invention; 
         FIG. 8  is a diagram illustrating a configuration of a vacuum film forming apparatus by a plasma support sputtering process; 
         FIG. 9  is a diagram illustrating a tape peeling test (a grid tape peeling test according to JIS D0202-1988); 
         FIG. 10  is a diagram illustrating a configuration of a vacuum film forming apparatus by an electron beam heating vacuum deposition process; 
         FIG. 11  is a diagram illustrating a configuration of a vacuum film forming apparatus by an ion plating process; and 
         FIG. 12  is a schematic longitudinal sectional view of a conventional analysis element chip. 
     
    
    
     EMBODIMENTS FOR CARRYING OUT THE INVENTION 
     In the following, an embodiment of the invention is described referring to the accompanying drawings. 
     An analysis chip according to the embodiment is used in an analysis device for analyzing a specimen based on a change in the resonance angle of surface plasmon resonance, or is used in an analysis device for measuring fluorescence emitted by excitation of a specimen or a fluorescent material labeled to a specimen by an evanescent wave based on surface plasmon resonance. The analysis chip is a sensor chip using a Kretschmann configuration. 
     Specifically, as shown in  FIGS. 1 through 3 , the analysis chip is provided with a prism part  20  having a gold film  25  formed thereon, and a channel member  12  which is cooperative with the prism part  20  to form a channel  13  for flowing a sample solution containing a specimen. 
     The prism part  20  generates surface plasmon resonance on the gold film  25  by reflecting excitation light incident into the prism part  20  on the gold film  25 . Specifically, the prism part  20  includes a prism main body  21  into which excitation light for generating surface plasmon is incident, and the gold film  25  formed on a specified surface  23  of the prism main body  21 . 
     The prism main body  21  includes, as the surfaces thereof, an incident surface  22 , the reflection surface (specified surface)  23 , and an exit surface  24 ; and is made of transparent glass or a transparent resin. 
     The incident surface  22  is used for incidence of excitation light to be outputted from a light source (not shown) of a surface plasmon resonance fluorescence analysis device into the prism main body  21 , in the case where the analysis chip  10  is placed in the surface plasmon resonance fluorescence analysis device for analyzing a specimen. Further, the reflection surface  23  is used for reflecting excitation light incident from the incident surface  22  into the prism main body  21  on the gold film  25  formed on the specified surface  23 , in the case where the analysis chip  10  is placed in the surface plasmon resonance fluorescence analysis device for analyzing a specimen. Further, the exit surface  24  is used for outputting excitation light reflected on the reflection surface  23  (specifically, on the gold film  25  formed on the reflection surface  23 ) to the outside of the prism main body  21 , in the case where the analysis chip  10  is placed in the surface plasmon resonance fluorescence analysis device for analyzing a specimen. 
     The prism main body  21  in the embodiment includes only a prism. However, the invention is not limited to the above. For instance, as shown in  FIG. 4 , a prism main body  21 A may include a prism  211 , and a substrate  212  having a gold film  25  formed thereon. In the above modification, the gold film  25  is not formed on the prism  211 , but is formed on the substrate  212 . Specifically, the substrate  212  has the same refractive index as the prism  211 , and has the gold film  25  formed on a surface (one surface of the substrate  212  in the thickness direction thereof)  23 . The substrate  212  has a back surface (the other surface of the substrate  212  in the thickness direction thereof)  212   b  facing the prism  211 , and is disposed on a specified surface  211   a  of the prism  211  via a matching oil  213 . Specifically, the substrate  212  is disposed in such a manner that the surface  23  faces the gold film  25  and that the back surface  212   b  faces the specified surface  211   a  of the prism  211  via the matching oil  213 . Thus, with use of the prism main body  21 A provided with the prism  211 , and the substrate  212  having the gold film  25  formed thereon, it is possible to keep using the prism  211  by replacing only the substrate  212 , in the case where it is necessary to replace the gold film  25  due to peeling off, smear, or damage of the gold film  25 . This is advantageous in reducing the cost. 
     As also shown in  FIG. 5 , the prism main body  21  is provided with a mixed layer portion (a mixed layer)  28  having a predetermined thickness from the reflection surface  23  toward the inner side of the prism main body  21 , in a direction orthogonal to the reflection surface  23 . 
     The mixed layer portion  28  is formed by ions of gold for the gold film  25  entering into the prism main body  21  from the reflection surface  23 . Specifically, in the mixed layer portion  28 , a material (the aforementioned glass or resin) constituting the other portion (a portion other than the mixed layer portion  28 ) of the prism main body  21 , and gold atoms constituting the gold film  25  coexist. 
     The mixed layer portion  28  has a thickness of 10 nm or smaller. As far as the mixed layer portion  28  has the aforementioned thickness, it is easy to determine the thickness of the gold film  25  suitable for surface plasmon resonance in the prism part  20 . Specifically, the refractive index of the mixed layer portion  28  is different from the refractive index of the other portion of the prism main body  21 . Accordingly, in the case where the thickness of the mixed layer portion  28  is larger than 10 nm, it is required to consider the refractive index or the thickness of the mixed layer portion  28  in deriving the thickness of the gold film  25  suitable for surface plasmon resonance. This makes it difficult to derive the thickness of the gold film  25  suitable for surface plasmon resonance in the prism part  20 . On the other hand, in the case where the thickness of the mixed layer portion  28  is not larger than 10 nm, it is possible to derive the thickness of the gold film  25  suitable for surface plasmon resonance only from the refractive index of the other portion of the prism main body  21 , without considering the refractive index or the thickness of the mixed layer portion  28 . In the embodiment, the thickness of the mixed layer portion  28  is a thickness of a region in which gold is present in the prism main body  21 . 
     The prism main body  21  may have a shape other than a trapezoidal shape (see  FIG. 2 ) in section as described in the embodiment. The prism main body  21  may have such a configuration that the prism main body  21  includes, as the surfaces thereof, the incident surface  22 , the reflection surface  23 , and the exit surface  24 ; excitation light incident from the incident surface  22  into the prism main body  21  is reflected on the reflection surface  23  (specifically, on the gold film  25  formed on the reflection surface  23 ); and the reflected excitation light is outputted to the outside from the exit surface  24  without diffuse reflection within the prism main body  21 . 
     The gold film  25  is a thin film made of gold and is formed on the reflection surface  23  of the prism main body  21 . The gold film  25  forms the mixed layer portion  28  by causing a part of a large amount of gold atoms constituting the gold film  25  to enter into the prism main body  21  from the reflection surface  23 . The gold film  25  amplifies an evanescent wave to be generated by reflection of excitation light on the gold film  25  in the prism part  20 . Specifically, as compared with a configuration, in which an evanescent wave is generated by causing total reflection of excitation light on a reflection surface  23  without forming a gold film  25 , the configuration of forming a gold film  25  on a reflection surface  23 , and generating surface plasmon resonance on the gold film  25  is advantageous in enhancing an electric field to be formed near the reflection surface  23 . The film thickness of the gold film  25  is 100 nm or smaller for generating surface plasmon resonance. Preferably, the gold film  25  is formed on the reflection surface  23  with a film thickness of not smaller than 30 nm but not larger than 70 nm. 
     Further, biologically active substances  26  for capturing a specimen (e.g. a specific antigen) contained in a sample solution are immobilized on a surface (a surface of the gold film  25  opposite to the prism main body  21 )  25   a  of the gold film  25 . The biologically active substances  26  in the embodiment are antibodies. The biologically active substances  26  are immobilized on the surface  25   a  of the gold film  25  by surface treatment. Specifically, the biologically active substances  26  are immobilized in a region, on the surface  25   a  of the gold film  25 , in contact with a sample solution that flows through the channel  13 , in the case where the channel member  12  forms the channel  13  in cooperation with the prism main body  21 . It should be noted that the biologically active substances  26  shown in  FIG. 2  and in  FIG. 4  are schematic examples, and the exemplified shapes of the biologically active substances  26  are different from the actual shape. 
     The thus-configured gold film  25  is formed on the reflection surface  23  by a vacuum film forming process such as an electron beam heating vacuum deposition process, a resistance heating vacuum deposition process, a magnetron sputtering process, a plasma support sputtering process, an ion assist vapor deposition process, or an ion plating process. 
     The channel member  12  is formed on the reflection surface  23  (specifically, on the gold film  25 ) of the prism main body  21 , and forms the channel  13  in cooperation with the prism main body  21 . The channel member  12  is made of a transparent resin. The channel member  12  in the embodiment is a plate-shaped member extending in a horizontal direction. 
     The channel  13  has a detecting portion  13   a  in which antigen-antibody reaction is performed, and guiding portions  13   b  for guiding a sample solution from the outside of the analysis chip  10  to the detecting portion  13   a  or guiding a sample solution from the detecting portion  13   a  to the outside of the analysis chip  10 . The detecting portion  13   a  is surrounded by a groove formed in a back surface (the lower surface in  FIG. 2 )  12   b  of the channel member  12 , and the gold film  25  formed on the prism main body  21 . Specifically, in the detecting portion  13   a,  a sample solution flows over the surface (a surface where the biologically active substances  26  are immobilized)  25   a  of the gold film  25  in contact with the surface  25   a.  One end of each of the guiding portions  13   b  is opened toward a surface (the upper surface in  FIG. 1 )  12   a  of the channel member  12 , and the other end (the end opposite to the one end) thereof is connected to the detecting portion  13   a.  Communicating one of the guiding portions  13   b,  the detecting portion  13   a,  and the other of the guiding portions  13   b  in this order forms the one channel  13 . 
     Further, the channel member  12  has a seal member  15  in the groove of the back surface  12   b  constituting the channel  13 . The seal member  15  surrounds the detecting portion  13   a  in a horizontal direction, and is adhesively attached to an inner surface of the groove in the back surface  12   b  of the channel member  12  and to the gold film  25  of the prism part  20 , in the case where the channel member  12  is joined to the prism main body  21  from the gold film  25  side. This configuration prevents leakage of a sample solution from a joined portion between the channel member  12  and the prism part  20 . The seal member  15  in the embodiment is a so-called O-ring. The seal member  15  is not limited to an O-ring. For instance, as shown in  FIG. 6 , the seal member may be a both-side adhesive sheet  15 A having such a shape that a through portion corresponding to the detecting portion  13   a  of the channel  13  is formed. In the modification, the seal member is disposed between the channel member  12  and the prism part  20 . 
     The channel member  12  is joined to the prism part  20  by a fixing member such as a clamp or a screw so that the back surface  12   b  is pressingly mounted on the reflection surface  23  (specifically, on the gold film  25 ) of the prism part  20 . The above configuration makes it easy to detach the channel member  12  and the prism part  20  from each other, and is advantageous in replacing the prism part  20  due to smear or damage of the gold film  25 . 
     The channel member  12  may not be detachably joined to the prism part  20 . Specifically, the channel member  12  may be adhesively joined to the prism part  20 , or may be joined to the prism part  20  by laser welding or ultrasonic welding. Further, as far as the channel member  12  and the prism part  20  are liquid-tightly joined, the seal member  15  for surrounding the detecting portion  13   a  may be omitted. 
     The thus-configured analysis chip  10  is produced as follows. 
     &lt;Production of Prism Part&gt; 
     A prism main body (a prism in the embodiment)  21  of a predetermined shape is prepared (Step S 1 ). The prism main body  21  is placed in a film forming position of, e.g., a vacuum film forming apparatus. Then, a gold film  25  is formed on a reflection surface  23  by the vacuum film forming apparatus. Specifically, the prism main body  21  is placed in a vacuum atmosphere, and gold (gold ions) in an ionized state is supplied onto the reflection surface  23 . By the supply, the gold film  25  is formed substantially on the entirety of the reflection surface  23 . In the embodiment, the gold film  25  is formed on the reflection surface  23  by a vacuum film forming process such as an electron beam heating vacuum deposition process, a magnetron sputtering process, a plasma support sputtering process, an ion assist vapor deposition process, or an ion plating process. 
     Specifically, the prism main body  21  is placed in a vacuum chamber of a vacuum film forming apparatus, and the air in the vacuum chamber is exhausted. By the exhaustion, the inside of the chamber is brought to a vacuum atmosphere. The vacuum film forming apparatus generates gold ions to be supplied onto the reflection surface  23  in the chamber of a vacuum atmosphere, and supplies the gold ions onto the reflection surface  23 . In the supply, the gold to be supplied onto the reflection surface  23  may not be in a completely ionized state. 
     A part of a large amount of gold ions that reached the reflection surface  23  (namely, gold ions having an energy higher than a predetermined energy) enters into the prism main body  21  from the reflection surface  23 , whereby a mixed layer portion  28  is formed on the prism main body  21  (Step S 2 ). As gold ions are continued to be supplied onto the reflection surface  23 , the gold is deposited on the outer side of the reflection surface  23  in such a manner as to continue from a layer of gold that has entered into the prism main body  21  (into a mixed layer). Then, when the gold is deposited up to a predetermined thickness, formation of the gold film  25  is completed (Step S 3 ). In the thus-formed gold film  25 , the gold atoms entered into the prism main body  21  from the reflection surface  23  act as an anchor. As a result, the reflection surface  23  of the prism main body  21  made of a resin or glass, and the gold film  25  are firmly adhesively attached to each other. In the adhesion, as the amount of gold ions to be supplied onto the reflection surface  23  increases, the amount of gold that enters from the reflection surface  23  per unit area increases. Further, as the energy of gold ions that have reached (collided) the reflection surface  23  increases, the distance by which the gold ions enter into the prism main body  21  from the reflection surface  23  increases. In other words, the thickness of the mixed layer portion  28  increases. 
     As described above, a prism part  20  provided with a prism main body  21  having a mixed layer portion  28  formed thereon, and a gold film  25  is produced. 
     &lt;Production of Analysis Chip&gt; 
     Biologically active substances  26  are immobilized in a predetermined region on a surface  25   a  of the gold film  25  by surface treatment (Step S 4 ). The predetermined region is a portion (region) corresponding to a detecting portion  13   a  of a channel  13  in the case where a channel member  12  is joined to the prism part  20 . 
     The channel member  12  of a predetermined shape is prepared (Step S 5 ). The channel member  12  is abutted against the prism part  20  from the gold film  25  side. In this state, the channel member  12  is fixedly mounted to the prism part  20  by, e.g., screws (Step S 6 ), whereby an analysis chip  10  is fabricated. 
     In the thus-configured analysis chip  10 , a part of the gold film  25  is entered into the prism main body  21  (into the mixed layer portion  28 ). This is advantageous in enhancing adhesion of the gold film  25  to the prism main body  21 . The adhesion suppresses the gold film  25  from peeling off from the prism main body  21 . Specifically, a part of a large amount of gold atoms constituting the gold film  25  is entered into the prism main body  21  and forms the mixed layer portion  28  to thereby firmly join the prism main body  21  and the gold film  25 . By the joining, the adhesion strength of the gold film  25  to the prism main body  21  is enhanced, as compared with a gold film which is formed on a specified surface without formation of a mixed layer portion  28  on a prism main body  21 . 
     The prism part  20 , the analysis chip  10  including the prism part  20 , and the method for producing the prism part  20  of the analysis chip  10  according to the invention are not limited to the embodiment. It should be appreciated that various modifications are applicable, as far as such modifications do not depart from the scope of the present invention. 
     In the embodiment, in forming a gold film  25  on a reflection surface  23 , a step of forming a mixed layer portion  28  by implanting gold ions into the reflection surface  23 , and a step of forming a portion of the gold film  25  on the outer side of the reflection surface  23  are sequentially carried out by a vacuum film forming process. The invention is not limited to the above. For instance, a mixed layer portion  28  may be formed in advance by implanting gold ions from a reflection surface  23  by an ion implantation process, and thereafter, a portion of a gold film  25  on the outer side of the reflection surface  23  may be formed by a vacuum film forming process. 
     EXAMPLE 1 
     In this section, in order to evaluate the performance of suppressing peeling off of a gold film  25  from a prism part  20  of an analysis chip  10  according to the embodiment, comparison is made between a prism part  20  having a mixed layer portion  28 , and a prism part having substantially the same configuration as the embodiment except that a mixed layer is not formed. 
     A prism part  20  as Example 1 was fabricated (produced) as follows. 
     A gold film  25  of 50 nm-thickness was formed on a reflection surface  23  of a prism main body  21  made of LaF71 (crown-based glass containing lanthanum) by a plasma support sputtering process. 
     In the following, the plasma support sputtering process is described. 
     Film formation by the plasma support sputtering process is performed by, e.g., an apparatus  30  as shown in  FIG. 8 . The apparatus  30  is provided with a vacuum chamber  31 , a holder  32  for holding a prism main body  21 , a target holder  33  constituting a cathode and for holding a gold target G for generating gold ions, a shutter  34  disposed at an appropriate position on a path of gold ions flowing from the gold target G toward the prism main body  21  held on the holder  32 , a support coil  35  disposed at an appropriate position on the path of gold ions, a first RF power source  36  for applying RF energy to the cathode, and a second RF power source  37  for applying RF energy to the support coil  35 . 
     In the thus-configured apparatus  30 , the prism main body  21  (or a substrate  212 ) is held on the holder  32  in a state that the reflection surface  23  faces the gold target G, and the air is exhausted to thereby bring the inside of the vacuum chamber  31  into a predetermined vacuum atmosphere. Then, argon gas is fed into the vacuum chamber  31 , and electric discharge is generated by applying RF energy to the cathode by the first RF power source  33 , whereby gold is sputtered from the gold target G by the reaction as represented by the following reaction formula. 
       Au+Ar + →Au + +e − +Ar + 
 
     When the shutter  34  is opened, the gold ions and the gold (gold which has not been ionized) sputtered out of the gold target G are energized by high energy electrons while passing through the support coil  35  to which RF energy is applied by the second RF power source  37 . Then, the gold ions having high energy collide with the reflection surface  23 . By the collision, the gold ions enter into the prism main body  21  from the reflection surface  23 , and a mixed layer portion  28  is formed. By continuing sputtering, the gold is deposited on the reflection surface  23 , and a gold film  25  is formed. In the film formation, the high frequency electric power to be applied is 100 W on the cathode side, and 50 w on the support coil side. 
     A cross section of the prism main body  21  having the gold film  25  formed thereon by the aforementioned plasma support sputtering process was observed by FIB-TEM, and element analysis was performed by EDS. As a result of the observation, it was confirmed that a region containing gold atoms (i.e. the mixed layer portion  28 ) was formed in the range of about 9 nm from the reflection surface  23 , on the reflection surface  23  side of the prism main body  21 . 
     On the other hand, as a comparative example, a gold film of 50 nm-thickness was formed on a reflection surface  23  of a prism main body  21  by a resistance heating vacuum deposition process without a step of ionizing gold. Similarly to the above, a cross section of the prism main body  21  was observed by FIB-TEM, and element analysis was performed by EDS. As a result of the observation, it was confirmed that no region containing gold atoms was found near the reflection surface  23  of the prism main body  21 . In other words, a mixed layer portion was not formed. 
     A tape peeling test (a grid tape peeling test according to JIS D0202-1988) was performed, and the adhesion strengths of the gold films were evaluated. 
     In the test, as shown in  FIG. 9 , grid-like cuts  17  at an interval of 1 mm were formed in each reflection surface  23  having the gold film  25  thereon in a direction from above the gold film  25 . Then, after an adhesive tape  18  was attached to each of the gold films  25 , the adhesive tape  18  was peeled off by tearing or pulling the adhesive tape  18  in an obliquely upward direction at an angle of 45° with respect to the reflection surface  23 . The adhesion strengths (adhesiveness) of the gold films  25  to the reflection surfaces  23  were evaluated by the number of square segments of the gold films  25  that did not peel off from the reflection surfaces  23  by the tearing operation. 
     The result is shown in the following table 1. 
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 1 
               
               
                   
                   
               
               
                   
                 0-th time 
                 1st time 
                 2nd time 
                 10th time 
               
               
                   
                 tearing 
                 tearing 
                 tearing 
                 tearing 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Example 1 
                 100/100 
                 100/100 
                 100/100 
                 100/100 
               
               
                 Comparative 
                 100/100 
                  38/100 
                  16/100 
                  0/100 
               
               
                 Example 
               
               
                   
               
            
           
         
       
     
     As a result of the test, it was confirmed that a prism part  20  provided with a mixed layer portion  28  is advantageous in firmly adhering a gold film  25  to a reflection surface  23 . 
     EXAMPLE 2  
     In this example, a prism part  20  provided with a mixed layer portion  28  was produced by forming a gold film  25  of 45 nm-thickness on a reflection surface  23  of a prism main body  21  made of E48R (cycloolefin polymer resin) by an electron beam heating vacuum deposition process. 
     In the following, the electron beam heating vacuum deposition process is described. 
     Film formation by the electron beam heating vacuum deposition process is performed by, e.g., an apparatus  40  as shown in  FIG. 10 . The apparatus  40  is provided with a vacuum chamber  41 , a holder  42  for holding a prism main body  21 , an electron gun  44  for discharging electrons from a filament  43  and loaded with a gold ingot G, and a shutter  45  disposed at an appropriate position on a path of gold or gold ions flowing from the gold ingot G toward the prism main body  21  held on the holder  42 . 
     In the thus-configured apparatus  40 , the prism main body  21  (or a substrate  212 ) is held on the holder  42  in such a state that a reflection surface  23  faces the gold ingot G, and the air is exhausted to thereby bring the inside of the vacuum chamber  41  into a predetermined vacuum atmosphere. Then, a predetermined acceleration voltage and an emission current are applied to the electron gun  44  for discharging electrons from the filament  43 , and a magnetic field formed near the electron gun  44  guides the electrons to the gold ingot G. When the discharged electrons are irradiated onto the gold ingot G (collide with the gold ingot G), the gold evaporates. Then, when the shutter  45  is opened, the evaporated gold passes through the flow of electrons that are irradiated onto the gold ingot G while being supplied onto the reflection surface  23 . During this operation, collision ionization as represented by the following formula occurs, whereby the gold is ionized. 
       Au+e − →Au + +e −+e   − 
 
     By the collision of ionized gold with the reflection surface  23 , the gold ions enter into the prism main body  21  from the reflection surface  23 , and form a mixed layer portion  28 . By continuing discharge of electrons by the electron gun  44 , the gold is deposited on the reflection surface  23 , and a gold film  25  is formed. In the film formation, the acceleration voltage to be applied to electron beams is 6 kV, and an emission current is 120 mA. 
     A cross section of the prism main body  21  having the gold film  25  formed thereon by the aforementioned electron beam heating vacuum deposition process was observed by FIB-TEM, and element analysis was performed by EDS. As a result of the observation, it was confirmed that a region (i.e. the mixed layer portion  28 ) containing gold atoms was formed in the range of about 3 nm from the reflection surface  23 , on the reflection surface  23  side of the prism main body  21 . 
     On the other hand, as a comparative example, a gold film of 45 nm-thickness was formed on a reflection surface  23  of a prism main body  21  by a resistance heating vacuum deposition process without a step of ionizing gold. Similarly to the above, a cross section of the prism main body  21  was observed by FIB-TEM, and element analysis was performed by EDS. As a result of the observation, it was confirmed that no region containing gold atoms was found near the reflection surface  23  of the prism main body  21 . 
     A tape peeling test (a grid tape peeling test according to JIS D0202-1988) was performed with respect to the two prism parts, and the adhesion strengths of the gold films were evaluated in the same manner as Example 1. 
     The result is shown in the following table 2. 
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 0-th time 
                 1st time 
                 2nd time 
                 10th time 
               
               
                   
                 tearing 
                 tearing 
                 tearing 
                 tearing 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Example 2 
                 100/100 
                 100/100 
                 100/100 
                 100/100 
               
               
                 Comparative 
                 100/100 
                  48/100 
                  26/100 
                  12/100 
               
               
                 Example 
               
               
                   
               
            
           
         
       
     
     As a result of the test, it was confirmed that a prism part  20  provided with a mixed layer portion  28  is advantageous in firmly adhering a gold film  25  to a reflection surface  23 , as well as Example 1. 
     EXAMPLE 3  
     In this example, a prism part  20  provided with a mixed layer portion  28  was produced by forming a gold film  25  of 40 nm-thickness on a reflection surface  23  of a prism main body  21  made of BK7 (white sheet glass) by an ion plating process. 
     In the following, the ion plating process is described. 
     Film formation by the ion plating process is performed by, e.g., an apparatus  50  as shown in  FIG. 11 . The apparatus  50  is provided with a vacuum chamber  51 , a holder  52  for holding a prism main body  21 , a Faraday cup  53  for detecting an ion current near the holder  52 , a thoria tungsten filament  54  for discharging electrons, a mesh anode  55  for accelerating the discharged electrons, a tungsten board  56  for heating a gold ingot G, and a shutter  57  disposed at an appropriate position on a path of gold or gold ions flowing from the gold ingot G toward the prism main body  21  held on the holder  52 . 
     In the thus-configured apparatus  50 , the prism main body  21  (or a substrate  212 ) is held on the holder  52  in such a state that a reflection surface  23  faces the gold ingot G, and the air is exhausted to thereby bring the inside of the vacuum chamber  51  into a predetermined vacuum atmosphere. Then, in response to application of an alternate-current voltage to the thoria tungsten filament  54  for discharging electrons, the electrons travel toward the mesh anode  55 . In this state, the shutter  57  is opened, and the gold ingot G placed on the tungsten board  56  is heated to evaporate. By the above operation, the evaporated gold passes through the flow of electrons from the thoria tungsten filament  54  toward the mesh anode  55  while being supplied onto the reflection surface  23 . During this operation, collision ionization as represented by the following formula occurs, whereby the gold is ionized. 
       Au+e − →Au + +e − +e − 
 
     By the collision of ionized gold with the reflection surface  23 , the gold ions enter into the prism main body  21  from the reflection surface  23 , and form a mixed layer portion  28 . By continuing discharge of electrons by the thoria tungsten filament  54 , the gold is deposited on the reflection surface  23 , and a gold film  25  is formed. In the film formation, the electric power of an evaporation source is 500 W, the voltage to be applied for ionization is 0.5 kV, and an emission current is 500 mA. 
     A cross section of the prism main body  21  having the gold film  25  formed thereon by the aforementioned ion plating process was observed by FIB-TEM, and element analysis was performed by EDS. As a result of the observation, it was confirmed that a region (i.e. the mixed layer portion  28 ) containing gold atoms was formed in the range of about 6 nm from the reflection surface  23 , on the reflection surface  23  side of the prism main body  21 . 
     On the other hand, as a comparative example, a gold film of 40 nm-thickness was formed on a reflection surface  23  of a prism main body  21  by a resistance heating vacuum deposition process without a step of ionizing gold. Similarly to the above, a cross section of the prism main body  21  was observed by FIB-TEM, and element analysis was performed by EDS. As a result of the observation, it was confirmed that no region containing gold atoms was found near the reflection surface  23  of the prism main body  21 . 
     A tape peeling test (a grid tape peeling test according to JIS D0202-1988) was performed with respect to the two prism parts, and the adhesion strengths of the gold films were evaluated in the same manner as Example 1 and Example 2. 
     The result is shown in the following table 3. 
     
       
         
           
               
               
               
               
               
             
               
                   
                 TABLE 3 
               
               
                   
                   
               
               
                   
                 0-th time 
                 1st time 
                 2nd time 
                 10th time 
               
               
                   
                 tearing 
                 tearing 
                 tearing 
                 tearing 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Example 3 
                 100/100 
                 100/100 
                 100/100 
                 100/100 
               
               
                 Comparative 
                 100/100 
                  32/100 
                  8/100 
                  0/100 
               
               
                 Example 
               
               
                   
               
            
           
         
       
     
     As a result of the test, it was confirmed that a prism part  20  provided with a mixed layer portion  28  is advantageous in firmly adhering a gold film  25  to a reflection surface  23 , as well as Example 1 and Example 2. 
     SUMMARY OF THE EMBODIMENT 
     The following is a summary of the embodiment 
     A prism part of an analysis chip according to an embodiment is a prism part to be included in an analysis chip for use in an analysis device for analyzing a specimen utilizing surface plasmon resonance, the analysis chip being operative to generate the surface plasmon resonance, the prism part being cooperative with a channel member to form a channel for flowing a sample solution containing the specimen. The prism part is provided with a prism main body into which excitation light for generating the surface plasmon resonance is incident, and a gold film formed on a specified surface of the prism main body. The prism main body has a mixed layer in which gold and a material constituting the prism main body coexist along the specified surface on which the gold film is formed, and on an inner side of the specified surface. 
     In the above configuration, forming a mixed layer in which gold constituting a gold film and a material constituting a prism main body coexist is advantageous in increasing the adhesion strength of the gold film to the prism main body, as compared with a prism part, in which a gold film is formed on a specified surface of a prism main body, without a mixed layer. In other words, the adhesion strength of a gold film to a prism main body is enhanced by interaction between the gold atoms residing in a mixed layer, and the gold atoms residing on the outer side of a specified surface. 
     In the prism part having the above configuration, for instance, the mixed layer may be formed by ions of gold for the gold film entering into the prism part from the specified surface in the formation of the gold film on the specified surface. 
     As described above, causing a part of a gold film to enter into a prism main body (into a mixed layer) is advantageous in obtaining high adhesion of the gold film to the prism main body. This suppresses peeling off of the gold film from the prism main body. Specifically, forming a mixed layer by causing a part of a large amount of gold atoms constituting a gold film to enter into a prism main body firmly joins the prism main body and the gold film. This is advantageous in enhancing the adhesion strength of the gold film to the prism main body. 
     In the above configuration, preferably, the mixed layer may have a thickness of  10  nm or smaller. 
     A mixed layer having the above thickness is advantageous in easily determining the thickness of a gold film suitable for surface plasmon resonance in the prism part. Specifically, the refractive index of a mixed layer is different from the refractive index of the other portion (a portion other than the mixed layer) of a prism main body. Accordingly, if the thickness of a mixed layer exceeds 10 nm, it is required to take into consideration of the refractive index or the thickness of a mixed layer in deriving the thickness of a gold film suitable for surface plasmon resonance. This makes it difficult to derive the thickness of a gold film suitable for surface plasmon resonance in a prism part  20 . On other hand, a mixed layer having a thickness of 10 nm or smaller is advantageous in deriving the thickness of a gold film suitable for surface plasmon resonance only from the refractive index of the other portion of a prism main body, without considering the refractive index or the thickness of the mixed layer. 
     Forming the gold film having a thickness of not smaller than 30 nm but not larger than 70 nm in the prism part having the above configuration is advantageous in generating an enhanced electric field of an intensity sufficient for detecting a specimen in the vicinity of the gold film, in the case where surface plasmon resonance is generated in the gold film of the analysis chip incorporated with the prism part. 
     Further, an analysis chip according to the embodiment is an analysis chip for use in an analysis device for analyzing a specimen utilizing surface plasmon resonance, the analysis chip being operative to generate the surface plasmon resonance. The analysis chip is provided with a prism part, and a channel member which is cooperative with the prism part to form a channel for flowing a sample solution containing the specimen. The prism part has a prism main body into which excitation light for generating the surface plasmon resonance is incident, and a gold film formed on a specified surface of the prism main body. The prism main body has a mixed layer in which gold and a material constituting the prism main body coexist along the specified surface on which the gold film is formed, and on an inner side of the specified surface. 
     In the above configuration, forming a mixed layer in which gold constituting a gold film and a material constituting a prism main body coexist is advantageous in obtaining high adhesiveness of a gold film with respect to the prism main body. This suppresses peeling off of the gold film from the prism main body. Specifically, the adhesion strength of a gold film to a prism main body is enhanced by interaction between the gold atoms residing in a mixed layer, and the gold atoms residing on the outer side of a specified surface. 
     Further, a method for producing a prism part according to the embodiment is a method for producing a prism part to be included in an analysis chip for use in an analysis device for analyzing a specimen utilizing surface plasmon resonance, the analysis chip being operative to generate the surface plasmon resonance, the prism part being cooperative with a channel member to form a channel for flowing a sample solution containing the specimen. The method is provided with a film forming step of forming a gold film on a specified surface of a prism main body, the prism main body being prepared in advance for allowing incidence of excitation light for generating the surface plasmon resonance. In the film forming step, gold in an ionized state is supplied onto the specified surface in such a manner that the gold in an ionized state enters into the prism main body from the specified surface. 
     The above configuration is advantageous in producing a prism part in which peeling off of a gold film from a prism main body is suppressed. Specifically, in the step of forming a gold film, a part of a large amount of gold atoms constituting the gold film is entered into the prism main body to thereby obtain a prism part in which the adhesion strength between the prism main body and the gold film is large. 
     Specifically, in the film forming step, the gold film is formed by one of film forming processes including an electron beam heating vacuum deposition process, a magnetron sputtering process, a plasma support sputtering process, an ion assist deposition process, and an ion plating process. This configuration is advantageous in supplying gold ions onto a specified surface in forming a gold film in such a manner that gold in an ionized state enters into a prism main body. 
     INDUSTRIAL APPLICABILITY 
     As described above, a prism part of an analysis chip, an analysis chip including the prism part, and a method for producing the prism part of the analysis chip of the invention are useful in easily handling an analysis chip to be used in a surface plasmon resonance analysis device or a surface plasmon resonance fluorescence analysis device, and is suitable for suppressing peeling off of a gold film from a prism main body.