Abstract:
The present invention provides an ultra-mini and low cost refractive index measuring device applicable to biochemical measurements of an extremely minute amount of a sample. The refractive index measuring device uses a photonic crystal without any requirement of an external spectrograph or the like. The micro sensor device according to the present invention includes a light source emitting light with a single wavelength, a microcavity in which a resonant wavelength varies depending on a position thereof. A refractive index of a material to be measured is measured based on positional information by detecting a transmitting position of light changing in response to a change of a refractive index of the measured material. The micro sensor device according to the present invention enables measurement of a refractive index of a material to be measured without using a large-scale spectrograph.

Description:
CLAIM OF PRIORITY  
       [0001]     The present application claims priority from Japanese application JP 2005-203967 filed on Jul. 13, 2005, the content of which is hereby incorporated by reference into this application.  
       FIELD OF THE INVENTION  
       [0002]     The present invention relates to a structure of a micro sensor device which is applicable for biochemical measurement or other chemical measurements and is also capable of measurement of a refractive index of a minute amount of liquid, and to a method of manufacturing the micro sensor device and a method of applying the micro sensor device.  
       BACKGROUND OF THE INVENTION  
       [0003]     It is required in the fields of biochemistry and medical measurements to measure low molecular-weight molecules such as glucose, ions, cell communication molecules, and peptides, and high molecular-weight molecules such as hormones, proteins and DNAs. In the biochemical measurements as described above, generally a quantity of samples is small, and a method is required for obtaining as much information as possible with a possibly minimum quantity of samples because minimally invasive checking is required.  
         [0004]     As a means for measurement, a method is utilized in which a pair of molecules specifically binding to each other such as a pair of an antigen and an antibody, a pair of DNS sequences complimentary to each other, and a pair of a ligand and a receptor are used and one of the molecules in each pair is detected. In most of the cases, an analyte is detected by labeling a sample with a fluorescent material or a radioactive material and detecting the luminescence or the radioactivity. However, the method for using a label has the following problems relating to a process of labeling an analyte: (1) a sample is required to be diluted; (2) it takes time; (3) an activity of an analyte changes; and (4) specificity of an analyte changes. Therefore, a method for using a label has been sought. As described above, the biochemical measurement requires a method in which a sample required for measurement is minimal and labeling is not required.  
         [0005]     Examples of the prior art-based technique for biochemical measurement utilizing specific binding of molecules and not requiring labeling include the method utilizing the surface plasmon resonance as disclosed, for instance, in “SPR DETECTION SYSTEM MEDIUM A” (online), Basic Principle of Technology, disclosed on a website of Biacore (searched on Jun. 13, 2005), &lt;http://www.biacore, co.jp/3 — 1 — 3.shtml&gt; searched on Jun. 13, 2006). A principle of this method is illustrated in  FIGS. 1A  to  1 C. In the method cited above, as illustrated in  FIG. 1A , one of a pair of molecules specifically binding to each other is fixed to an Au film on a surface of a sensor chip in advance. When an analyte is allowed to flow into a flow cell, the measuring objective molecules bond with the fixed molecules as illustrated in  FIG. 1A . When such binding occurs, a refractive factor becomes larger locally at a place where the binding occurs. The change of the refractive index is detected through the surface plasmon. When light is directed to a face of the Au thin film opposite to the face to which the one of the molecules is fixed, the surface plasmon is excited under specific conditions. However, under the condition allowing for excitation of the surface plasmon, intensity of reflected light becomes lower. When a refractive index changes, the conditions allowing for excitation of the surface plasmon also change, and an angle at which intensity of the reflected light becomes lower change as shown in  FIG. 1B . (The change is illustrated with the reflection light I and II in  FIG. 1B ).  FIG. 1C  illustrates that a change of the reflection light can be detected as a signal indicating a change of time during which the sample is allowed to flow in a flow cell. Therefore, by measuring angular distributions of intensities of the reflection light, a change of the refractive factor on the surface, namely, binding between one of the pair of the molecules specifically binding with the analyte in the sample can be detected. The principle of this method is based on detection of binding between biological molecules with high sensitivity by detecting a change of a refractive index on a surface of a sample via the surface plasmon phenomenon. However, the method of measuring a change of a refractive index by making use of the surface plasmon phenomenon has some problems in that the optical system inevitably becomes relatively larger with the cost high, in that the size reduction is difficult, and in that there is a limit in reducing a quantity of a sample to be measured.  
         [0006]     A method using a photonic crystal has been studied on a technique enabling measurement of a refractive index with a minute amount of a sample. Examples of a method for measuring a refractive index using a photonic crystal include, for instance, a method described in OPTICS LETTER, Vol. 29, page 1093. A principle of the refractive index measurement using a photonic crystal described in the cited reference is now described below. The photonic crystal is a multi-dimensional periodic structure combining two or more mediums with different refractive indexes at a period of wavelength order. In the photonic crystal as described above, there is a wavelength range where light cannot propagate in the photonic crystal, namely, a frequency band called a photonic band gap. For instance, when light having a wavelength corresponding to the band gap is directed from outside to a photonic crystal, the light is completely reflected on the surface of the crystal because the light cannot be propagated inside of the crystal.  
         [0007]      FIG. 2  illustrates a state in which a two-dimensional photonic crystal with a band gap is configured by piercing round holes in a shape of a triangular lattice on an SOI (silicon on insulator of a SiO 2  substrate), and light is confined when a point defect, namely a non uniformity defect is provided in the periodic structure. Since the periodic structure is disturbed at a point defect, even light having a wavelength in the band gap can be present. However, since there is not defect around the point defect in the photonic crystal, the light can not propagate to outside, and is reflected and confined within the point defect. That is to say, the photonic crystal at and around a point defect forms a microcavity, and light having a specific wavelength is firmly confined therein in the steady state (referred to as resonant mode).  
         [0008]     When light is introduced into the photonic crystal microcavity as illustrated in  FIG. 2 , only light having a wavelength corresponding to the resonant mode passes through the resonator to form a sharp peak as shown in  FIG. 3 . In other words, only the light having a specific wavelength passes through the resonator and the light having other wavelengths is reflected. The wavelength at the resonant peak varies depending on, for instance, a refractive index of a substance forming the photonic crystal at and around the point defect.  
         [0009]      FIG. 4  illustrates a spectrum described in OPTICS LETTER, vol. 29, page 1093.  FIG. 4  shows changes of spectrum, in a case where liquid is injected into a round hole on a two-dimensional photonic crystal with a point defect as shown in  FIG. 2 , when a refractive index n of the liquid is changed to 1.446, 1.448, 1.450, 1.452, and 1.454. As illustrated in  FIG. 4 , a peak of the spectrum changes in correspondence to a very small change of the refractive index of the liquid, and it is understood that the refractive index can be detected by measuring the peak wavelength. In this figure, the two dimensional photonic crystal is shown by way of example. However, the same effect can be obtained also by using a one-dimensional photonic crystal having a structure in which two different layers with different refractive indexes are superimposed alternately, or a three-dimensional photonic crystal having a structure in which a periodic structure is three-dimensional if liquid serving as a sample can be introduced into the photonic crystal structure.  
         [0010]     It is possible to build a resonator without using a photonic crystal. A photonic crystal resonator has the feature in which a size of the resonator is as very small as of wavelength order. Therefore, it is possible to detect a refractive index with a minute quantity of a sample. As described above, the photonic crystal microcavity allows for use of a minimal quantity of a sample for biochemical measurement. In addition, a detector having a micro detection area provides the possibility of integration of sensors and measurement at an atomic size level.  
       SUMMARY OF THE INVENTION  
       [0011]     In the refractive index measuring method using the photonic crystal microcavity as described above, a refractive index is determined by a wavelength in the resonant mode. However, a light source having a broad band and a spectral device such as a diffraction grating are required, which inevitably leads to scaling up of a whole system. Besides, the cost is high since a number of component parts are required.  
         [0012]     In order to solve the problems described above, an object of the present invention is to provide a ultra mini-size and low cost refractive index measuring device capable of measuring an extremely small amount of a sample using a photonic crystal and not requiring any external spectrograph.  
         [0013]     A means for solving the problems in the conventional methods is described below with reference to  FIGS. 5A  to  5 C.  
         [0014]     An example illustrated in  FIG. 5A  is configured of light having a wavelength λ 0 , three units of one-dimensional photonic crystal microcavities  1   A ,  1   B  and  1   C  having different sizes of defects and receiving the light, and a detector array including photo detectors  2   A ,  2   B  and  2   C  detecting light passing through the microcavities  1   A ,  1   B  and  1   C , respectively. The photonic crystal portion of each microcavity, for example, is configured of a plurality of thin plates formed from a Si substrate through semiconductor processes to each have a predetermined thickness and to be spaced apart from each other at a predetermined interval, and a thin plate having intermediate portions with different thicknesses. In addition, a space between the thin plates is filled with liquid of a substance having a refractive index of n.  
         [0015]     A left-hand portion of  FIG. 5B  illustrates characteristics of the photonic crystal portion of each microcavity when a refractive index of the liquid of the measured substance is n 1 . When the refractive index is n 1 , a peak of a transmission spectrum of the photonic crystal of the one-dimensional photonic crystal microcavity  1   A  coincides with the wavelength λ 0 . However, peaks of transmission spectrum of the other one-dimensional photonic crystal microcavities  1   B  and  1   C  do not coincide with the wavelength λ 0 . As a result, as illustrated in a right-hand portion of  FIG. 5B , when light having a wavelength λ 0  is directed from outside with the liquid of the measured substance having a refractive index n 1  being filled therein, the light directed to the one-dimensional photonic crystal microcavity  1   A  passes therethrough, and is detected by the photo detector device  2   A . On the other hand, the light directed to the other one-dimensional photonic crystal microcavities  1   B  and  1   C  are reflected by the photonic crystals, so that it do not reach the photo detector devices  2   B  and  2   C . Therefore, only the photo detector device  2   A  associated with the one-dimensional photonic crystal microcavity  1   A  reacts.  
         [0016]     On the other hand,  FIG. 5C  illustrates characteristics of a portion of a photonic crystal in each microcavity when a refractive index of liquid of measured substance is n 2 . In association with a change of the refractive index of the liquid as a measured substance, the spectrums of the photonic crystals in the one-dimensional photonic crystal microcavities  1   A ,  1   B  and  1   C  also change. In this case, as shown by the transmission spectrums in a left-hand portion of  FIG. 5C , a peak of the transmission spectrum of the photonic crystal of the one-dimensional photonic crystal microcavity  1   B  coincides with the wavelength λ 0 . Therefore, as illustrated in a right-hand portion of  FIG. 5C , only the photo detector device  2   B  associated with the one-dimensional photonic crystal microcavity  1   B  reacts.  
         [0017]     Hence, when liquid having an unknown refractive index is filled and measured in refractive index, it can be determined that, when the photo detector device  2   A  reacts, the unknown refractive index of the liquid is n 1 , and when the photo detector device  2   B  reacts, the unknown refractive index of the liquid is n 2 .  
         [0018]     As described above, in the present invention, information on a refractive index of liquid as a measured substance can be obtained without using a spectrograph, because a change of the refractive index of the liquid is converted to positional information and then detected.  
         [0019]     Although only the concept is illustrated in  FIGS. 5A, 5B  and  5 C, needless to say, necessary frequency bands and resolutions should be obtained by making optimal designs concerning such parameters as a structure of an individual photonic crystal or the number of arrays according to conditions required in each measuring system.  
         [0020]     As described above, the present invention can provide an ultra mini-size and low cost refractive index measuring device capable of measuring an extremely small amount of a sample using a photonic crystal and not requiring any external spectrograph, and of being applicable to biochemical measurement or the like. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0021]      FIGS. 1A  to  1 C are conceptual diagrams illustrating a sensor using a surface plasmon therein;  
         [0022]      FIG. 2  is a conceptual diagram illustrating a state in which light is entrapped in a defect in a photonic crystal, provide a microcavity;  
         [0023]      FIG. 3  is a graph illustrating a light transmission spectrum provided by the photonic crystal having a defect (s);  
         [0024]      FIG. 4  is a graph illustrating the relationship between a peak of the wavelength of light from a two-dimensional photonic crystal microcavity and the refractive indexes of filled liquid;  
         [0025]      FIGS. 5A  to  5 C illustrate a principle of measurement of a refractive index with the micro sensor device according to the present invention;  
         [0026]      FIGS. 6A  to  6 D illustrate a micro sensor device according to a first embodiment of the present invention;  
         [0027]      FIG. 7  is a diagram illustrating a cross-sectional structure of a one-dimensional photonic crystal according to the first embodiment;  
         [0028]      FIG. 8  is a graph illustrating the relationship between ethanol concentration (weight percent) of a water-ethanol mixture liquid and a refractive index of the mixture liquid;  
         [0029]      FIG. 9  is a graph illustrating transmission spectrums provided by the one-dimensional photonic crystal microcavities  31  to  34  in the first embodiment;  
         [0030]      FIG. 10  is a graph illustrating the relationship between the peak wavelengths in transmission spectrums provided by the one-dimensional photonic crystal microcavities  31  to  34  in the first embodiment and a refractive index of liquid filled therein;  
         [0031]      FIG. 11  is a graph illustrating the relationship between concentration of a mixture liquid and outputs of four photodiodes in the first embodiment;  
         [0032]      FIGS. 12A and 12B  illustrate a second embodiment of the present invention in which a micro sensor device is built with a two-dimensional photonic crystal;  
         [0033]      FIG. 13  illustrates a third embodiment of the present invention in which a liquid refractive index sensor is built with the micro sensor device according to the present invention; and  
         [0034]      FIG. 14  illustrates a fourth embodiment of the present invention in which the micro sensor device according to the present invention is built in a microchemical chip. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
     First Embodiment  
       [0035]      FIGS. 6A, 6B ,  6 C and  6 D illustrate a structure of a refractive index sensor according to a first embodiment of the present invention.  FIG. 6A  is a plane view of the sensor,  FIG. 6B  is a cross-sectional view taken along the direction of arrows A-A in  FIG. 6A ,  FIG. 6C  is a cross-sectional view taken along the direction of arrows B-B in  FIG. 6A , and  FIG. 6D  is a cross-sectional view taken along the direction of arrows C-C in  FIG. 6A .  
         [0036]     In  FIG. 6A , designated at reference numeral  1  is a substrate. Reference numeral  2  denotes a sample cell formed from a Si substrate through semiconductor processes to have a one-dimensional photonic crystal section  100  and a sample introductory section  200 . The sample cell  2  can be fixed on a top surface of the substrate  1  keeping a predetermined positional relationship with the substrate  1  by means of stoppers  3  provided on an external circumferential surface of the substrate  1 . After completion of measurement, the sample cell  2  can be unfixed and discarded. In the sample cell  2 , the one-dimensional photonic crystal section  100  and the sample introductory section  200  are connected to each other at their bottoms on the Si substrate of the sample cell  2 . The one-dimensional photonic crystal section  100  is formed with thin plates  101  and  102  as illustrated in  FIG. 5A  to have inside intervals therebetween different from each other from place to place. In other words, four different defective structures are provided in this case. The one-dimensional photonic crystal microcavities  31 ,  32 ,  33  and  34  are configured to have different characteristics according to their defective structures, respectively. The sample cell  2  has opening sections  300  and  400 . The opening section  300  includes, on the substrate  1 , a semiconductor laser  10  having an oscillation wavelength 1400 nm and a waveguide  20  dividing the outgoing light from the semiconductor laser  10  into four portions and guiding the divided light into a corresponding one of the four one-dimensional photonic crystal microcavities  31 ,  32 ,  33  and  34 . The opening section  400  includes photo diodes  41 ,  42 ,  43  and  44  formed on the substrate  1  and being equivalent to the photo detector devices  2   A ,  2   B  and  2   C  shown in  FIG. 5A . The photo diodes  41 ,  42 ,  43  and  44  correspond to the one-dimensional photo crystal microcavities  31 ,  32 ,  33  and  34 , respectively.  
         [0037]     Since  FIG. 6B  is a cross-sectional view taken along line A-A in  FIG. 6A , only an end face of the sample introductory section  200  and those of the two thin plates  101  are shown. It is understood from  FIG. 6B  that the sample cell  2  is placed on a top surface of the substrate  1  and relative positions of the sample cell  2  and the substrate  1  are kept with the stoppers  3 .  
         [0038]     Since  FIG. 6C  is a cross-sectional view taken along line B-B in  FIG. 6A , an end face of the sample introductory section  200  is not shown. A portion of a cross section of the waveguides  20  are shown in the opening section  300 , and also cross sections of the thin plates  101  and  102  of the one-dimensional photonic crystal section  100  are shown. Side faces of other thin plates  101  located farther than the thin plates  101  described above are shown between the thin plates  101 . In addition, a cross section of the photo diode  44  is shown in the opening section  400 . It is understood from  FIG. 6C  that the opening sections  300  and  400  of the sample cell  2  are through-holes and the waveguide  20  and the photo diode  44  are placed in the opening section  300  and in the opening section  400  on the upper surface of the substrate  1  respectively. An end face of the stopper  3  is also shown.  
         [0039]     Since  FIG. 6D  is a cross-sectional view taken along line C-C in  FIG. 6A , an end face of the sample introductory section  200  is not shown. A portion of a cross section of the semiconductor laser  10  and that of the waveguide  20  are shown in the opening section  300 , and also cross sections of the thin plates  101  and  102  of the one-dimensional photonic crystal section  100  are shown. Side faces of other thin plates  101  located at farther positions are shown between the thin plates  101  described above. In addition, an end face of the photo diode  43  is shown in the opening section  400 . It is understood from  FIG. 6D  that the opening sections  300  and  400  of the sample cell  20  are through-holes, the semiconductor laser  10  and the waveguide  20  are provided at the opening  300  and the photodiode  42  is provided at the opening  400  on the upper surface of the substrate  1 . In addition, end faces of the stoppers  3  are shown at this position.  
         [0040]     When the refractive index sensor according to the first embodiment of the present invention described with reference to  FIGS. 6A, 6B ,  6 C and  6 D is used, a sample to be measured is dropped in the sample sensor  200 . The dropped sample flows toward the one-dimensional photonic crystal section  100 , and then flows into between the thin plates  101  and  102  because of the capillary phenomenon. As a result, as described with reference to  FIG. 5 , light directed to the one-dimensional photonic crystal section  100  via the semiconductor laser  10  and the waveguide  20  is detected by any one of the one-dimensional photonic crystal microcavities  31 ,  32 ,  33  and  34  corresponding to a refractive index of the sample to be measured as well as by a corresponding one of the photo diodes  41 ,  42 ,  43  and  44 . The sample to be measured is dropped into the sample introductory section  200 , because the size of the one-dimensional photonic crystal section  100  is small, so that when directly dropped into the microcavities due, the sample liquid may overflows from the one-dimensional photonic crystal section  100  to contaminate the peripheral areas. Although a capacity of the sample introductory section  200  is as small as possible to enable measurement with an extremely minute amount of a sample, it is necessary to take into consideration a structure of a dropper for dropping a sample and a mechanism for dropping.  
         [0041]     As understood by referring to  FIGS. 6A, 6B ,  6 C and  6 D, in the first embodiment of the present invention, a sample to be measured is only introduced into the sample introductory section  200  and one-dimensional photonic crystal section  100  of the sample cell  2 . Therefore, after measurement for one sample to be measured is completed, a secondary sample to be measured can be measured immediately by taking off the sample cell  2  from the substrate  1  and then a new sample cell  2  is mounted onto the substrate  1 .  
         [0042]      FIG. 7  illustrates a detailed configurational example of a defect structure portion, i.e., a microcavity of the one-dimensional photonic crystal in order to detail its detecting operation. A thickness of each of the thin plates  101  and  102  is denoted by sign H, which is common to the whole one-dimensional photonic crystal section  100  (the microcavities  31  to  34 ), that is, H is 300 nm. A distance between the thin plates  101  and  102  is denoted by sign L, which is also common to the whole one-dimensional photonic crystal section  100  (the microcavities  31  to  34 ), that is, L is 777.8 nm. A distance between the thin plates  101  is denoted by sign D, which represents a width of a defective portion of the one-dimensional photonic crystal section  100 . Each width varies depending on the one-dimensional photonic crystal microcavities. The microcavities  31 ,  32 ,  33  and  34  have widths of 1540 nm, 1555 nm, 1570 nm and 1585 nm, respectively. A height of the one-dimensional photonic crystal section  100  is denoted by sign X, which is 10 μm.  
         [0043]     A process for producing a structure of the one-dimensional photonic crystal microcavities illustrated in  FIG. 6  is described before explanation of a detecting operation by the microcavities. At first, a SiO 2  film having a thickness of 500 nm is formed by sputtering on a Si substrate. Then, a positive resist (ZEP-520) film is formed on the SiO 2  film, and the opening sections  300  and  400  are patterned by electron beam drawing. Next, the SiO 2  film is etched with Ar and C 4 F 8 . After the resists are incinerated with thermal UVO 3  for exfoliation, a through-hole is formed by dry etching the Si substrate using SF 6  and O 2 . The openings  300  and  400  are formed as described above. Next, negative resist (SAL601-SR7) film is provided on the SiO 2  film and the sample cell  2  is patterned by electron beam drawing. Then, the SiO 2  substrate is etched with Ar and C 4 F 8 . After the resists are incinerated with thermal UVO 3  for exfoliation, high aspect ratio ICP dry etching is performed on the Si substrate using SF 6  and O 2 . In this step, a bottom electrode is cooled down to −100° C. or below with liquid nitrogen. The one-dimensional photonic crystal microcavities are produced as described above.  
         [0044]     On the other hand, a Si substrate is prepared for the substrate  1 , and then a film for the waveguide  20  is produced by using polymer at a position corresponding to the opening section  300  of the sample cell  2 . Specifically, a polyimide film is prepared by spin-coating polyimide. A thickness of the polyimide film is 5 μm. Then, the waveguides  20  is formed by photolithography and etched using the dry-etching technique. Also the stopper  3  is formed along with the above processes. In succession, the semiconductor laser  10  corresponding to the shape of the waveguides is mounted at a position corresponding to the opening section  300 . Finally, at a position corresponding to the opening  400 , a photo diode array including the photo diodes  31 ,  32 ,  33  and  34  associated with the defective portions is mounted on the substrate.  
         [0045]     In an operating demonstration, as illustrated in  FIG. 7 , liquid as a material to be measured was filled into spacing of the Si structure and measured. This time, the material used for the measurement is a mixture of water and ethanol.  
         [0046]      FIG. 8  is a graph illustrating the relationship between a refractive index and ethanol concentration (weight percent) of a water-ethanol mixture at a temperature of 15° C. The data used herein is described in A Manual for Chemistry (Basic) (Handbook for Chemistry (Basic version)); 3rd edition; page 2; Chemical Society in Japan. In this document, it is described that the refractive index of the mixture varies within a range of 1333 to 1367 depending on the ethanol concentration (weight ratio).  
         [0047]      FIG. 9  shows that widths of the defect portions D of the one-dimensional photonic crystal microcavities are 1540 nm, 1555 nm, 1570 nm and 1585 nm when the refractive index of the mixed liquid is 1,335, that is, shows the transmission spectrums of the one-dimensional photonic crystal microcavities  31 ,  32 ,  33  and  34 . The wavelengths of the transmission spectrums are shifted with each other depending on the difference of the defective portion D. A distance between peaks is designed to be about a half value width.  
         [0048]      FIG. 10  illustrates the relationship between peak wavelengths of the transmission spectrums of the one-dimensional photonic crystal microcavities  31 ,  32 ,  33  and  34  and the refractive index of the mixture. It indicates that the peak wavelengths substantially linearly increase with an increase in refractive index.  
         [0049]     Operations in the first embodiment are described with reference to  FIGS. 8, 9 , and  10 . Light emitted from the semiconductor laser  10  is equally divided into four pieces of light through the waveguides  20 . The divided pieces of light are each directed to a corresponding one of the one-dimensional photonic crystal microcavities  31 ,  32 ,  33  and  34 . Spaces in the microcavities are filled with the water-ethanol mixture.  FIG. 8  shows that when a concentration of the ethanol is 10%, a refractive index of the mixture is 1.34. In  FIG. 10 , a wavelength 1400 nm of incident light is indicated by a dashed line, and the light passes through at an intersection point of the dashed line and solid lines. It is understood from  FIG. 10  that, when the refractive index of the mixture is 1.34, the light passes through the one-dimensional photonic crystal microcavity  33 . Therefore, only the photo diode  43  can detect signals, that is, the photo diodes  41 ,  42  and  44  do not detect the light.  
         [0050]      FIG. 11  illustrates outputs from the photo diodes  41 ,  42 ,  43  and  44  when a concentration of ethanol is changed on a 10%-basis in the range from 10% to 50%. A horizontal axis in  FIG. 11  indicates ethanol concentration and a vertical axis indicates detection outputs of the photo diodes  41 ,  42 ,  43  and  44 . It is confirmed that the detection outputs of the photo diodes  41 ,  42 ,  43  and  44  change in response to a change of a refractive index caused by a change of ethanol concentration, whereby changes of the refractive index can be detected. It is also confirmed that, even when any one of the peaks of the photonic crystal does not coincide exactly with 1400 nm for e.g. 30% or 40% of the concentration, since a certain amount of light passes through the microcavity because of extension of a line width of transmission spectrum peaks, a refractive index can be measured by comparing intensities of transmitted light with each other. This is probably because a distance between peaks of the transmission spectrums is about a half value width.  
       Second Embodiment  
       [0051]     In a second embodiment of the present invention, a two-dimensional photonic crystal, instead of the one-dimensional photonic crystal, is used as the photonic crystal section  100 .  
         [0052]     A two-dimensional photonic crystal  25  in the second embodiment is mainly composed of a Si layer with a thickness of 200 nm and a SIO substrate configured of a SiO 2  layer with a thickness of 1 μm.  FIG. 12A  is a plan view illustrating the two-dimensional photonic crystal  25 , and  FIG. 12B  is a cross-sectional view illustrating the two-dimensional photonic crystal  25  taken along line A-A in  FIG. 12A . Reference  250  denotes the SiO 2  layer, and side walls  201  of a sample flow path are formed on both side faces of the Si layer on the SiO 2  layer. Columns  202  each having a diameter of 250 nm are provided in triangular form between the side walls  201  to form a photonic crystal. A distance between centers of adjacent columns  202  (a lattice constant) is 400 nm. Point defects are introduced by making the diameters of the columns  202   a ,  202   b ,  202   c , and  202   d  smaller. The diameters of the columns  202   a ,  202   b , and  202   c  are 150 nm, 100 nm, and 50 nm, respectively, and the column  202   d  is lacked. A thickness of the two-dimensional photonic crystal  25  is as substantially small as 200 nm, and also a coupler  21  is made of Si. The size of a waveguide of the coupler is 200 nm×200 nm. In  FIG. 12 , the semiconductor layer  10  and the waveguide  20 , photonic microcavities  31 ,  32 ,  33  and  34 , and the photodiodes  41 ,  42 ,  43 , and  44  are shown as in  FIG. 6 . The configuration shown in  FIG. 12  is substantially the same as that described in the first embodiment excluding the point that the two-dimensional photonic crystal is used in place of the one-dimensional photonic crystal.  
       Third Embodiment  
       [0053]     A configuration of a refractive index sensor according to a third embodiment of the present invention is shown in  FIGS. 13A  to  13 C.  FIG. 13A  is a plan view of the refractive index sensor,  FIG. 13B  is a cross-sectional view illustrating the refractive index sensor taken along line A-A in  FIG. 13A , and  FIG. 13C  is a cross-sectional view illustrating the refractive index sensor taken along line B-B in  FIG. 13A . Also in the third embodiment, as in the first embodiment, the sample cell  2  is removably held on the substrate  1  via the stoppers  3  as guides. Provided in the sample cell  2  are a sample introductory section  200 , a one-dimensional photonic crystal section  100  contiguous to the section  200 , and opening sections  300  and  400 . In the third embodiment, the one-dimensional photonic crystal section  100  provided in the sample cell  2  is formed with linear thin plates  101 ,  102 , and  103 . The thin plates  101 ,  102 , and  103  are equally spaced apart from each other as in the second embodiment. However, a space between the opposite thin plates  103  varies as they go in the longitudinal direction. In the third embodiment, an LED array  301  composed of a plurality of LEDs  302  arranged at predetermined intervals is provided in the opening section  300  in place of the semiconductor laser  10  and the waveguide  20  used in the first embodiment. Furthermore, provided in the opening section  400  are a lens array  401  in which a plurality of lenses  402  are arrayed at predetermined intervals and a photodiode array in which a plurality of photodiodes are arrayed at predetermined intervals are used in place of the photodiodes  41 ,  42 ,  43 , and  44  used in the first embodiment. Needless to say, the interval between the adjacent LEDs  302 , the interval between the adjacent lenses  402 , the interval between the adjacent LEDs  302 , and the interval between the adjacent photodiodes are equal to one another.  
         [0054]     In the first and second embodiments, the semiconductor laser  10  and the waveguide  20  are used to split light from one light source and supply the split light to photonic crystal microcavities. In the third embodiment, the LEDs  302  each emitting light with the same wavelength are arranged in array and used as a light source. Action of the one-dimensional photonic crystal is the same as that described in the first embodiment. However, in the configuration according to the first embodiment, elements each having a different defect width are coupled to each other in the first embodiment, whereas a width of a defect section continuously varies in a direction perpendicular to a light-passing direction.  
         [0055]     Also in the third embodiment, a sample to be measured is dropped into the sample introductory section  200  of the sample cell  2 . The sample flows into the one-dimensional photonic crystal section  100  because of the capillary phenomenon, and the refractive index is detected by the method detailed in the first embodiment.  
       Fourth Embodiment  
       [0056]     An example in which the micro sensor device according to the present invention is mounted on a microchemical chip is described in a fourth embodiment of the present invention. The microchemical chip is used in a technique for realizing various operations in chemical reactions such as mixing, transport, heating, and extracting of a sample on a chip by the MEMS technique. By realizing the operations on a chip, not only size reduction and availability of a minute amount of a sample, but also higher efficiency in chemical reactions provided by size reduction can be expected.  
         [0057]     As shown in  FIG. 14 , provided on a top surface of a microchemical chip  450  are a micro sensor device  456  of the present invention and a drain  457  in addition to a sample cell  451 , reagent cells  452 ,  453 , micro flow path  454 , and a heating section  455  for promoting chemical reactions.  
         [0058]     A sample introduced into the sample cell  451  is mixed with reagents supplied from the reagent cells  452 ,  453  in the heating section  455 , in which the mixture is heated to promote chemical reactions. A refractive index of the reaction product is measured by the micro sensor device  456 . As easily understood by referring to  FIG. 6A ,  FIG. 12A , and  FIG. 13A , it may be regarded that, in the fourth embodiment, the sample introductory section  200  shown in each of the embodiments above is replaced with the sample cell  451 , the reagent cells  452 ,  453 , the micro flow path  454 , and the heating section  455  for promoting reactions in the microchemical chip  450 . Therefore, it is necessary only to prepare a micro sensor device  456  in which the sample introductory section  200  and an end portion of the one-dimensional photonic crystal section  100  are cut off and to provide the micro sensor device  456  on the downstream side of the heating section  455  for promoting reactions in the microchemical chip  450 . In the first to third embodiments, the sample cell in which a measure sample flows, and the light source and the sensor portion are mounted on the respective different substrates. In this case, as with the first to third embodiments, the microchemical chip  450 , and a light source for the microchemical chip  450  and the sensor portion are mounted on respective different substrates. With this configuration, the microchemical chip  450  may be disposable.  
         [0059]     In the embodiments, while descriptions are mainly made of application to biochemical measurement, applications of the micro sensor device according to the present invention are not limited to those described above. That is, the micro sensor device according to the present invention may be applied also to chemical synthesis and analysis of environmental pollutants such as endocrine disturbing chemicals or dioxin. In any case, the present invention is applicable on the condition that a sample to be measured is provided as a liquid and changes of a refractive index of the sample can be detected as information.