Patent Publication Number: US-9903861-B2

Title: Device and method for detecting an analyte

Description:
REFERENCE TO SEQUENCE LISTING SUBMITTED VIA EFS-WEB 
     This application includes an electronically submitted sequence listing in .txt format. The .txt file contains a sequence listing entitled “2017-07-21 0033-1565PUS1 ST25.txt” created on Jul. 21, 2017 and is 1,608 bytes in size. The sequence listing contained in this .txt file is part of the specification and is hereby incorporated by reference herein in its entirety. 
     TECHNICAL FIELD 
     The present invention relates to a device and method for detecting an analyte. 
     BACKGROUND ART 
     In recent years, as an in-vitro diagnostic method, there has been proposed a diagnostic method utilizing presentation of color by localized surface plasmon resonance of colloidal gold. For example, in immunochromatography, there is proposed a method using colloidal gold having an antibody fixed thereto, as a tag-labeled particle. According to this method, when an antigen that is an analyte is contained in a specimen, the antigen and the tag-labeled particle are conjugated together to form a composite. The composite develops a moving bed and is captured by an antibody of a determination site. This causes the determination site to exhibit a red color. Whether the antigen is present or absent can be confirmed by confirming whether the determination site exhibits color. 
     For example, Japanese Patent Laying-Open No. 2009-210505 (PTD 1) discloses an immunological measurement kit aiming at application to immunochromatography. For example, Japanese National Patent Publication No. 2005-533246 (PTD 2) discloses a surface enhanced resonance Raman scattering (SERRS) active bead employed for identifying a target molecule. This bead includes aggregated metallic colloid and at least one SERRS active dye that are encapsulated in a polymer shell. 
     CITATION LIST 
     Patent Documents 
     PTD 1: Japanese Patent Laying-Open No. 2009-210505 
     PTD 2: Japanese National Patent Publication No. 2005-533246 
     SUMMARY OF INVENTION 
     Technical Problem 
     There constantly exists a need for a technique allowing an analyte to be detected with enhanced sensitivity, in other words, a technique allowing a trace amount of the analyte to be detected. According to the method disclosed in Japanese Patent Laying-Open No. 2009-210505 (PTD 1), whether a determination site exhibits color can be confirmed to conveniently confirm whether an antigen is present or absent. It is believed, however, that visually confirming whether color is exhibited requires that a specimen should contain an analyte of a concentration of some high extent, and requires the analyte in a large amount. 
     An object of the present invention is to provide a device and method allowing a trace amount of an analyte to be rapidly detected to contribute to overcoming the above issue. 
     Solution to Problem 
     The present invention in one aspect provides a detection device for detecting an analyte that may be contained in a specimen. The detection device comprises a plurality of metallic nanoparticles, a first light source, an objective lens, a photoreceiver, and a detector. The plurality of metallic nanoparticles are each modified with a host molecule allowing the analyte to specifically adhere thereto. The first light source emits polarized light for assembling the plurality of metallic nanoparticles together. The objective lens focuses and introduces the polarized light into a liquid containing a specimen and the plurality of metallic nanoparticles. The photoreceiver receives light from the liquid. The detector detects an analyte based on a signal received from the photoreceiver. 
     Preferably, the detection device further comprises an adjustment mechanism. The adjustment mechanism adjusts a distance between the objective lens and a gas-liquid interface of the liquid and a gas surrounding the liquid so that the objective lens has a focal point in the liquid in a vicinity of the gas-liquid interface. 
     Preferably, the detection device further comprises an optically transparent substrate holding the liquid. 
     Preferably, the plurality of metallic nanoparticles are each modified with a first host molecule. The detection device further comprises a substrate having a plurality of spots each having a second host molecule fixed thereto. 
     Preferably, the plurality of metallic nanoparticles include: a plurality of first metallic nanoparticles each modified with the first host molecule; and a plurality of second metallic nanoparticles each modified with the second host molecule. 
     Preferably, the analyte is a target DNA. The first and second host molecules are each a probe DNA hybridizing with the target DNA. 
     Preferably, the host molecule is a single type of host molecule. 
     Preferably, the analyte is an antigen. The host molecule is an antibody causing an antigen-antibody reaction with the antigen. 
     Preferably, the photoreceiver includes an image pick-up device for obtaining an image of the liquid. The detector detects the analyte based on the image obtained by the pickup device. 
     Preferably, the detection device further comprises a second light source emitting light for measuring the liquid&#39;s spectrum. The photoreceiver includes a spectroscope for measuring the liquid&#39;s spectrum. The detector detects the analyte based on a spectrum measured with the spectroscope. 
     Preferably, the second light source emits white light. 
     Preferably, the second light source emits substantially monochromatic light associated with one or more ranges corresponding to twice a full width at half maximum of a peak of localized surface plasmon resonance of the first metallic nanoparticle. 
     Preferably, the spectrum measured with the spectroscope is an adsorption spectrum of localized surface plasmon resonance. 
     Preferably, the spectrum measured with the spectroscope is a surface enhanced Raman scattering (SERS) spectrum. 
     Preferably, the target DNA is one of a first target DNA having a base sequence complementary to the probe DNA and a second target DNA having a base sequence partially different from the first target DNA. The photoreceiver includes a spectroscope for measuring a spectrum of the liquid. The detector determines whether the analyte is the first target DNA or the second target DNA, based on how the spectrum measured with the spectroscope varies with time. 
     Preferably, the first and second host molecules are first and second probe DNAs, respectively. The plurality of metallic nanoparticles are each modified with the first probe DNA. The detection device further comprises a substrate having a plurality of spots each having the second probe DNA fixed thereto. The analyte is one of a first target DNA having a base sequence complementary to the first and second probe DNAs and a second target DNA having a base sequence partially different from the first target DNA. The photoreceiver includes a spectroscope for measuring a spectrum of the liquid. The detector determines whether the analyte is the first target DNA or the second target DNA, based on how the spectrum measured with the spectroscope varies with time. 
     Preferably, the detection device further comprises a substrate having a micro channel passing the liquid. The light focused by the objective lens is introduced into the micro channel. 
     Preferably, a region of the substrate at least holding the liquid is super-hydrophilic. 
     Preferably, the plurality of metallic nanoparticles are dispersed in the liquid such that the plurality of metallic nanoparticles have a surface-to-surface distance larger than a sum of a size of the analyte and a size of the host molecule. 
     The present invention in another aspect provides a method for detecting an analyte that may be contained in a specimen. The method comprises the steps of: introducing into a liquid the specimen and a plurality of metallic nanoparticles each modified with a host molecule allowing the analyte to specifically adhere thereto; focusing via an objective lens polarized light output from a first light source, and irradiating the liquid with the polarized light focused, the polarized light being provided for assembling the plurality of metallic nanoparticles together; receiving light from the liquid by a photoreceiver; and detecting the analyte by a detector, based on the light received from the liquid. 
     Preferably, the analyte is an antigen. The host molecule is an antibody causing an antigen-antibody reaction with the antigen. 
     Preferably, the plurality of metallic nanoparticles are each modified with a first host molecule. The method further comprises the step of preparing a substrate having a plurality of spots each having a second host molecule fixed thereto. The step of introducing the specimen and the plurality of metallic nanoparticles into the liquid includes the step of introducing the specimen and the plurality of metallic nanoparticles into the liquid to be dropped on each of the plurality of spots. 
     Preferably, the plurality of metallic nanoparticles include: a plurality of first metallic nanoparticles each modified with a first host molecule; and a plurality of second metallic nanoparticles each modified with a second host molecule. 
     Preferably, the analyte is a target DNA. The first and second host molecules are each a probe DNA hybridizing with the target DNA. 
     Preferably, the step of receiving light includes the step of obtaining an image of the liquid by an image pick-up device. The step of detecting includes the step of detecting the analyte based on the image of the liquid. 
     Preferably, the method further comprises the step of irradiating the liquid with light output from a second light source for measuring a spectrum of the liquid. The step of receiving light includes the step of measuring the spectrum with a spectroscope. The step of detecting includes the step of detecting the analyte based on the spectrum. 
     Preferably, the step of irradiating includes the step of irradiating the liquid with substantially monochromatic light associated with one or more ranges corresponding to twice a full width at half maximum of a peak of localized surface plasmon resonance of the plurality of first metallic nanoparticles. 
     Preferably, the spectrum is an absorption spectrum of localized surface plasmon resonance. 
     Preferably, the spectrum is a surface enhanced Raman scattering (SERS) spectrum. 
     Preferably, the target DNA is one of a first target DNA having a base sequence complementary to the probe DNA and a second target DNA having a base sequence partially different from the first target DNA. The method further comprises the step of irradiating the liquid with light output from a second light source for measuring a spectrum of the liquid. The step of receiving light includes the step of measuring the spectrum with a spectroscope. The step of detecting includes the step of determining whether the analyte is the first target DNA or the second target DNA, based on how the spectrum varies with time. 
     Advantageous Effects of Invention 
     The present invention can thus provide a device and method allowing a trace amount of an analyte to be rapidly detected. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG. 1  is a schematic diagram for illustrating a mechanism of arranging a plurality of gold nanoparticles. 
         FIG. 2  is a figure for illustrating a 2-particle model of gold nanoparticles. 
         FIG. 3  (SEQ ID NOS: 1, 2, and 3) is a conceptual diagram for illustrating how gold nanoparticles are aggregated by DNA hybridization. 
         FIG. 4  schematically shows a configuration of a detection device according to a first embodiment of the present invention. 
         FIG. 5  is an enlarged view of a configuration in a vicinity of a kit of the detection device shown in  FIG. 4 . 
         FIG. 6  is a schematic diagram for illustrating how gold nanoparticles aggregate in a vicinity of a beam waist of a laser light shown in  FIG. 5 . 
         FIG. 7  is a flowchart for illustrating a method for detecting an analyte according to the first embodiment of the present invention. 
         FIG. 8  shows (A) an optical transmission image of a sample of a liquid mixture naturally dried on a substrate without undergoing light irradiation, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with a first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with a second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a complementary DNA (concentration: 10 nM, and volume: 5 μL), and (B) an optical transmission image of a sample of a liquid mixture naturally dried on a substrate without undergoing light irradiation, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a mismatched DNA (concentration: 1 μM, and volume: 5 μL). 
         FIG. 9  shows (A) an optical transmission image of a liquid mixture before light irradiation, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a complementary DNA (concentration: 10 nM, and volume: 5 μL), and (B) an optical transmission image of a liquid mixture before light irradiation, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a mismatched DNA (concentration: 1 μM, and volume: 5 μL). 
         FIG. 10  shows (A) an optical transmission image of a liquid mixture after light irradiation, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a complementary DNA (concentration: 10 nM, and volume: 5 μL), and (B) an optical transmission image of a liquid mixture after light irradiation, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a mismatched DNA (concentration: 1 μM, and volume: 5 μL). 
         FIG. 11  shows (A) an optical transmission image of a liquid mixture before light irradiation in a vicinity of a portion to exposed to a beam waist having a different position, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a complementary DNA (concentration: 10 nM, and volume: 5 μL), and (B) an optical transmission image of a liquid mixture before light irradiation in a vicinity of a portion to exposed to a beam waist having a different position, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a mismatched DNA (concentration: 1 μM, and volume: 5 μL). 
         FIG. 12  shows (A) an optical transmission image of a liquid mixture after light irradiation in a vicinity of a beam waist having a different position, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a complementary DNA (concentration: 10 nM, and volume: 5 μL), and (B) an optical transmission image of a liquid mixture after light irradiation in a vicinity of a beam waist having a different position, the liquid mixture being a mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a mismatched DNA (concentration: 1 μM, and volume: 5 μL). 
         FIG. 13  is an optical transmission image of a diluted dispersion liquid of a complementary DNA that has a different concentration (of 100 pM) on a substrate after light irradiation. 
         FIG. 14  presents successive photographic images (or optical transmission images) of a gas-liquid interface (in a vicinity of a beam waist) showing how a diluted dispersion liquid of a mismatched DNA (concentration: 1 μM) after light irradiation starts varies with time. 
         FIG. 15  presents successive photographic images (or optical transmission images) of a gas-liquid interface (in a vicinity of a beam waist) showing how a diluted dispersion liquid of a complementary DNA (concentration: 10 nM) after light irradiation starts varies with time. 
         FIG. 16  presents successive photographic images (or optical transmission images) of a gas-liquid interface of a diluted dispersion liquid of a complementary DNA (concentration: 100 pM) (in a vicinity of a beam waist). 
         FIG. 17  presents successive photographic images (or optical transmission images) of a gas-liquid interface of a diluted dispersion liquid of a complementary DNA (concentration: 1 pM) (in a vicinity of a beam waist). 
         FIG. 18  represents a result of calculating how a scattering spectrum varies with the number of adjacent gold nanoparticles. 
         FIG. 19  represents how an absorption spectrum of gold nanoparticles varies between before and after their aggregation. 
         FIG. 20  schematically shows a configuration of a detection device according to a second embodiment of the present invention. 
         FIG. 21  is a perspective view of an appearance of the detection device shown in  FIG. 20 . 
         FIG. 22  is a block diagram for specifically illustrating a configuration of the detection device shown in  FIG. 20 . 
         FIG. 23  is a flowchart for illustrating a method for detecting an analyte according to the second embodiment of the present invention. 
         FIG. 24  schematically shows a configuration of a detection device according to a fourth embodiment of the present invention. 
         FIG. 25  is a diagram for illustrating how a process in the detection device shown in  FIG. 24  proceeds. 
         FIG. 26  is a diagram for illustrating how a detection process using a DNA chip different from a DNA chip shown in  FIG. 25  proceeds. 
         FIG. 27  (SEQ ID NOS: 1-6) is a diagram for illustrating a probe DNA and four types of DNAs that can serve as an analyte and have mutually different base sequences. 
         FIG. 28  schematically shows a configuration of a detection device according to a fifth embodiment of the present invention. 
         FIG. 29  shows (A) successive photographic images (or optical transmission images) of a gas-liquid interface of a liquid mixture (in a vicinity of a beam waist) after light irradiation starts, the liquid mixture being a liquid mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a complementary DNA (concentration: 100 pM, and volume: 5 μL), and (B) how an absorption spectrum that the gas-liquid interface presents varies with time (0 second, 30 seconds, 60 seconds, 90 seconds, 120 seconds, 150 seconds, and 180 seconds after light irradiation starts). 
         FIG. 30  shows (A) successive photographic images (or optical transmission images) of a gas-liquid interface of a liquid mixture (in a vicinity of a beam waist) after light irradiation starts, the liquid mixture being a liquid mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a completely mismatched DNA (concentration: 100 pM, and volume: 5 μL), and (B) how an absorption spectrum that the gas-liquid interface presents varies with time (0 second, 30 seconds, 60 seconds, 90 seconds, 120 seconds, 150 seconds, and 180 seconds after light irradiation starts). 
         FIG. 31  shows (A) successive photographic images (or optical transmission images) of a gas-liquid interface of a liquid mixture (in a vicinity of a beam waist) after light irradiation starts, the liquid mixture being a liquid mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of a half mismatched DNA (concentration: 100 pM, and volume: 5 μL), and (B) how an absorption spectrum that the gas-liquid interface presents varies with time (0 second, 30 seconds, 60 seconds, 90 seconds, 120 seconds, 150 seconds, and 180 seconds after light irradiation starts). 
         FIG. 32  shows (A) successive photographic images (or optical transmission images) of a gas-liquid interface of a liquid mixture (in a vicinity of a beam waist) after light irradiation starts, the liquid mixture being a liquid mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM, and volume: 5 μL), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM, and volume: 5 μL), and a diluted dispersion liquid of an alternately mismatched DNA (concentration: 100 pM, and volume: 5 μL), and (B) how an absorption spectrum that the gas-liquid interface presents varies with time (0 second, 30 seconds, 60 seconds, 90 seconds, 120 seconds, 150 seconds, and 180 seconds after light irradiation starts). 
         FIG. 33  is a diagram for illustrating how the absorption spectra shown in  FIG. 29(B) ,  FIG. 30(B) ,  FIG. 31(B) , and  FIG. 32(B)  have peaks shifted. 
         FIG. 34  is a schematic diagram for illustrating a micro channel chip in a state before injection is started. 
         FIG. 35  is a schematic diagram for illustrating a micro channel chip in a state after injection is started. 
         FIG. 36  is a cross section of a micro channel chip  600  taken along a line XXXVI-XXXVI shown in  FIG. 35 . 
         FIG. 37  is an optical transmission image of a vicinity of a gas-liquid interface formed in the micro channel before light irradiation starts, as obtained via an objective lens having a magnification of 10 times. 
         FIG. 38  shows successive photographic images (or optical transmission images) of a gas-liquid interface formed in a micro channel having a liquid mixture (volume: 1 μL) introduced therein, that are obtained after light irradiation is started, as obtained in a vicinity of a beam waist via an objective lens having a magnification of 40 times, the liquid mixture being a liquid mixture of a dispersion liquid of gold nanoparticles modified with the first probe DNA (concentration: 5.0 nM), a dispersion liquid of gold nanoparticles modified with the second probe DNA (concentration: 5.0 nM), and a diluted dispersion liquid of a complementary DNA (concentration: 100 pM). 
         FIG. 39  is an enlarged view of a configuration in a vicinity of a kit using a hydrophobic substrate. 
         FIG. 40  is an optical transmission image of a diluted dispersion liquid of a complementary DNA on a hydrophobic substrate in a vicinity of a beam waist after light irradiation. 
         FIG. 41  is an enlarged view of a configuration in a vicinity of a kit super-hydrophilic substrate. 
         FIG. 42  is an optical transmission image of a diluted dispersion liquid of a complementary DNA on a super-hydrophilic substrate in a vicinity of a beam waist after light irradiation. 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     Hereinafter, an embodiment of the present invention will specifically be described with reference to the drawings. In the figures, identical or corresponding components are identically denoted and will not be described repeatedly. 
     In the present invention and its embodiment(s), a “metallic nanoparticle” is a metallic particle having a size on an order of nanometers. An “order of nanometers” includes a range of one to several hundreds nanometers and typically it ranges from 1 to 100 nm. The metallic nanoparticle is not limited in shape and may be a sphere or a rod as long as such metallic nanoparticles can be assembled by light irradiation. 
     In the present invention and its embodiment(s), a “metallic nanoparticle assembly” is an assembly formed by a plurality of aggregating metallic nanoparticles. 
     Furthermore in the present invention and its embodiment(s) an “analyte” may be a biomolecule and may be an organic molecule that is not limited to the biomolecule. Furthermore, the “analyte” may be a heavy metal ion. 
     In the present invention and its embodiment(s), a “host molecule” is a molecule allowing an analyte to specifically adhere thereto. Combinations of the host molecule allowing an analyte to specifically adhere thereto and the analyte include for example: antigen and antibody; sugar chain and protein; lipid and protein; a low molecule compound (ligand) and protein; protein and protein; single stranded DNA and single stranded DNA; and the like. When one component of such a specifically affinitive combination is an analyte, the other component of the combination can be used as a host molecule. In other words, if an antigen is an analyte, an antibody can be used as a host molecule. On the contrary, if an antibody is an analyte, an antigen can be used as a host molecule. Furthermore, in DNA hybridization, an analyte is a target DNA, and a host molecule is a probe DNA. Furthermore, an “antigen” can include allergen and virus. Furthermore, the present invention and its embodiment(s) also allow an antibody to be changed in type to change a type of allergen or virus detectable. The present invention and its embodiment(s) thus do not limit detectable allergen or virus in type. Furthermore, if the “analyte” is heavy metal, a molecule capable of capturing a heavy metal ion can be utilized as a host molecule. 
     In the present invention and its embodiment(s), a “first host molecule” and a “second host molecule” are host molecules that can specifically adhere to an analyte at different sites. For example, if a target DNA is an analyte, the first host molecule is a probe DNA hybridized from the 5′ end of the target DNA. The second host molecule is a probe DNA hybridized from the 3′ end of the target DNA. 
     For example, if an antigen is an analyte, the first host molecule is a primary antibody and the second host molecule is a secondary antibody. Note, however, that for example when an antigen is an analyte, a metallic nanoparticle having a surface modified with the primary antibody (or the first host molecule) may alone be used. 
     In the present invention and its embodiment(s), a “specimen” means a substance that may include a substance including an analyte or the analyte. The specimen may be biological specimens obtained for example from animals (e.g., human, cow, horse, pig, goat, chicken, rat, mouse, and the like). The biological specimen may include blood, tissues, cells, bodily secretions, bodily fluids, and the like, for example. Note that the “specimen” may also include their dilutions. 
     In the present invention and its embodiment(s) the term “white light” means continuous or pulsed light having a range in wavelength of a visible range-including, ultraviolet to near-infrared range (e.g., a range in wavelength of 200 nm to 1100 nm). 
     In the present invention and its embodiment(s) the term “monochromatic light” is light having a wavelength in a range corresponding to twice a full width at half maximum of a peak of localized surface plasmon resonance of a metallic nanoparticle assembly. The number of ranges corresponding to twice a full width at half maximum of a peak of localized surface plasmon resonance may be one or plural. 
     In the present invention and its embodiment(s) the term “polarization” means an electric field vector perpendicular to a direction in which an optical electromagnetic wave propagates. 
     In the present invention and its embodiment(s) the term “super-hydrophilicity” means that a tangent of a droplet held on a substrate and the substrate&#39;s surface form a contact angle of 10 degrees or smaller. 
     In the present invention and its embodiment(s) the term “dispersion” means that a host molecule or an analyte floats in a liquid, and the term includes a case in which the host molecule or the analyte is dissolved in the liquid. That is, a dispersion liquid can include a solution a dispersion medium can include a solvent. 
     First Embodiment 
     Arrangement of Gold Nanoparticles 
     In the following embodiment(s), a metallic nanoparticle is presented as a gold nanoparticle by way of example in form. The metallic nanoparticle is not limited to the gold nanoparticle, and may for example be a silver nanoparticle, a copper nanoparticle or the like. 
     The gold nanoparticle has an average diameter on a subnanometer order to a nanometer order (approximately 2 nm to 1000 nm), and it can for example be 2 nm to 500 nm, preferably 2 nm to 100 nm, more preferably 5 nm to 50 nm. 
     As will be described more specifically hereafter, a plurality of gold nanoparticles are captured by light-induced force and also arranged. In the present invention and its embodiment(s) “light-induced force” is used to correctively represent dissipative force, gradient force, and inter-object light-induced force. Dissipative force is a force generated in a dissipative process such as light scattering or light absorption as a momentum of light is imparted to a substance. Gradient force is a force moving an object with light-induced polarization to a stable point of an electromagnetic potential when the object is located in a nonuniform electromagnetic field. Inter-object light-induced force is a sum of a force attributed to a longitudinal electric field and a force attributed to a transverse electric field (or radiation field) that are generated from induced polarization caused in optically-excited plural objects. 
       FIG. 1  is a schematic diagram for illustrating a mechanism of capturing and arranging a plurality of gold nanoparticles.  FIG. 2  is a figure for illustrating a 2-particle model of gold nanoparticles. With reference to  FIG. 1  and  FIG. 2 , the plurality of gold nanoparticles  11  are dispersed in a liquid, e.g., in water. 
     Each of the plurality of gold nanoparticles  11  receives laser light  5 . Laser light  5  has a direction of polarization in the y-direction. In other words, laser light  5  is polarized in a direction substantially parallel to axis Ax passing through gold nanoparticles  11  through their respective centers. In that case, gold nanoparticles  11  are each electrically polarized in a direction parallel to the direction of polarization of laser light  5 . Thus, each gold nanoparticle  11  is captured at a vicinity of a stable point in electromagnetic potential of laser light  5 , i.e., in a vicinity of a beam waist of laser light  5 . Furthermore, gold nanoparticles  11  all have electric polarization in the same direction. This causes attractive force between adjacent gold nanoparticles  11 , as shown in  FIG. 2 . 
     It is assumed that the metallic nanoparticle is a spherical cell. In that case a response optical electric field can be described with an integral form of a Maxwell equation. A response electric field E i  is represented according to the following equation (1): 
     
       
         
           
             
               
                 
                   
                     
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     where i and j represent particle numbers of spherical cells, and M and L represent amounts associated with self-interaction. Susceptibility and electric field distributions in individual gold nanoparticles are assumed to be flat. An induced polarization P i  is represented according to the following equation (2):
 
 P   i =χ i (ω) E   i   (2).
 
     Note that a Drude model is applied to susceptibility χ. Susceptibility χ is represented according to the following equation (3): 
     
       
         
           
             
               
                 
                   
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     where χ b  represents background susceptibility, ω p  represents plasma energy, γ represents a nonradiative relaxation constant, and V f  represents electron velocity on the Fermi surface. Nonradiative relaxation constant γ is a value indicative of relaxation from light to other than light (e.g., heat). 
     In contrast, light-induced force is generally represented by the following equation (4) (T. Iida and H. Ishihara, Phys. Rev. B77, 245319 (2008)): 
     
       
         
           
             
               
                 
                   
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     G represents Green&#39;s function. In equation (5) at the right hand side the first term represents a gradient force attributed to incident light and the second term represents inter-object light-induced force. Gradient force attributed to incident light is proportional to light intensity gradient. In contrast, inter-object light-induced force is proportional to light intensity. Thus, light intensity gradient and light intensity of incident light can be controlled to adjust gradient force and inter-object light-induced force. 
     Again, with reference to  FIG. 1 , gold nanoparticles  11  dispersed in water each have a surface covered with a protecting group added when gold nanoparticles  11  are produced, and as the protecting group is ionized, the surface has a surface charge. The surface of each gold nanoparticle  11  has a single type of electric charge distributed thereon. This causes repulsive force between a plurality of gold nanoparticles  11 . When the trapping force caused via the radiation of the laser light (i.e., dissipative force and gradient force), the attractive force caused between the gold nanoparticles via electric polarization (i.e., inter-object light-induced force), and the repulsive force caused via the surface charge are in balance, the plurality of gold nanoparticles  11  can be arranged in a direction parallel to that in which laser light  5  is polarized. 
     &lt;Formation of Gold Nanoparticle Assembly&gt; 
     The gold nanoparticles are each modified with a host molecule. The host molecule has a site that can interact with a gold nanoparticle. The host molecule is fixed to a surface of the gold nanoparticle via the above site. The “interaction” refers to chemical bonding, Van der Waals force, electrostatic interaction, hydrophobic interaction, adsorption power, and the like. A site (or group) that can interact with gold is, but not limited to, a thiol group, for example. 
     In the present embodiment the analyte is a target DNA. In the presence of the target DNA, gold nanoparticles modified with a probe DNA are aggregated by DNA hybridization and form a gold nanoparticle assembly. In contrast, probe DNAs do not hybridize with each other. “Hybridization” means a reassociation reaction between two types of single stranded nucleic acids. In the present embodiment, a double strand is formed between two single strands of DNA that have complementary base sequences, as will be described hereinafter. However, hybridization is not limited thereto and includes formation of a double strand between one single strand of DNA and one RNA or between two RNAs. 
       FIG. 3  is a conceptual diagram for illustrating how gold nanoparticles are aggregated by DNA hybridization.  FIG. 3(A)  is a diagram showing one example of a base sequence of a probe DNA.  FIG. 3(B)  is a schematic diagram showing states before and after gold nanoparticles aggregate. 
     With reference to  FIG. 3(A) , the present embodiment employs a target DNA  18  as an analyte. Target DNA  18  is a single strand of DNA having a base sequence of 24 adenines for example. Probe DNAs  13  and  14  allowing target DNA  18  to specifically adhere thereto, are prepared. 
     Probe DNA  13  is a single strand of DNA having a  3 ′ end for example with a thiol group (represented as “SH”). Probe DNA  13  has between the thiol group and a 5′ end thereof a base sequence complementary to a base sequence of the target DNA closer to a 3′ end thereof. In the present embodiment the complementary base sequence is 12 thymines (represented as “T”). 
     Probe DNA  14  is a single strand of DNA having a 5′ end for example with a thiol group. Probe DNA  14  has between a 3′ end thereof and the thiol group a base sequence complementary to a base sequence of the target DNA closer to a 5′ end thereof. In the present embodiment the complementary base sequence is 12 thymines. 
     Then, with reference to  FIG. 3(B) , in the present embodiment, some gold nanoparticles  11  each have a surface modified with probe DNA  13  via the thiol group. The remaining gold nanoparticles  12  each have a surface modified with probe DNA  14  via the thiol group. A gold nanoparticle can be modified with a probe DNA for example in the following method: 
     Initially, 3.61 μM of thiolated DNA is added to a liquid having gold nanoparticles dispersed therein, and the liquid is then allowed to stand for example for 16 hours. Subsequently, sodium chloride and a phosphate buffer (pH: 7.0) are added to the above dispersion liquid to be 0.1 M and 10 mM and the liquid is then allowed to stand for example for 40 hours. Centrifugation is performed to settle nanoparticles and cleaning is performed. Note that the gold nanoparticle dispersion liquid may be a commercially available product or may be produced by using a gold ion (or gold complex ion) containing dispersion liquid and a reducing agent and thereby conducting a reductive reaction in the dispersion liquid. For example, a chlorauric acid dispersion liquid with citric acid added thereto may be used. 
     When gold nanoparticles  11  and  12  are introduced into a liquid containing target DNA  18 , probe DNA  13  and target DNA  18  hybridize together and so do probe DNA  14  and target DNA  18 . This causes gold nanoparticles  11 ,  12  to aggregate and thus form a gold nanoparticle assembly  10 . 
     &lt;Detection Device and Method&gt; 
       FIG. 4  schematically shows a configuration of a detection device according to the first embodiment of the present invention. With reference to  FIG. 4 , a detection device  100  includes an optical trapping light source  101  (a first light source), an illumination light source  102 , an optical component  104 , an objective lens  103 , a kit  20 , an image pick-up device  108  (a photoreceiver), a computation unit  106  (a detector), and an adjustment mechanism  112 . The x direction and the y direction each represent a horizontal direction. The x direction and the y direction are orthogonal to each other. The z direction represents a vertical direction. Gravity has a direction in the z direction downward. 
     Optical trapping light source  101  emits laser light  5  as polarized light for assembling gold nanoparticles  11  and  12 . Laser light  5  in kit  20  has a direction of polarization in the y-direction. Laser light  5  is radiated in the z direction upward to irradiate kit  20  (see  FIG. 5 ). 
     Optical trapping light source  101  is not specifically limited in configuration and may be any known light source used to operate nano-objects. Optical trapping light source  101  generates continuous near-infrared light (e.g., a wavelength of 1064 nm). Note that the polarization is not limited in type to linear polarization, and it may for example be circular polarization or elliptical polarization, and furthermore, it may be axially symmetric polarization. Axially symmetric polarization includes radial polarization and azimuthal polarization. 
     Illumination light source  102  emits light for illuminating a sample  30  (see  FIG. 5 ) within kit  20 . Illumination light source  102  is a light source emitting white light  6  for example. As one embodiment, a halogen lamp can be used as illumination light source  102 . Note that illumination light source  102  may be implemented as a monochromatic light source such as a laser light source. Note, however, that using a white light source as illumination light source  102  allows detection device  100  to be implemented at a low cost. 
     Optical component  104  includes a mirror, a prism, an optical fiber and/or the like for example. Optical component  104  is used to guide laser light  5  and white light  6  from optical trapping light source  101  and illumination light source  102 , respectively, to kit  20 . 
     Objective lens  103  receives laser light  5  from optical trapping light source  101  and focuses laser light  5  received. The light focused by objective lens  103  is radiated to irradiate sample  30 . Sample  30  is a liquid for example having introduced therein target DNA  18  and gold nanoparticles  11  and  12  having surfaces modified with probe DNAs  13  and  14 , respectively. Note that in the present embodiment laser light  5  having passed through objective lens  103  has an intensity for example of about 10% of that of laser light  5  output from optical trapping light source  101 . Note that objective lens  103  and optical component  104  are for example incorporated in the body of a microscope (not shown). 
     Furthermore, objective lens  103  is also used in order to collect light received from sample  30 . To efficiently collect light received from sample  30 , objective lens  103  preferably has a high numerical aperture (NA). Note that kit  20  may be irradiated with white light  6  output from illumination light source  102  via objective lens  103 . 
     Image pick-up device  108  obtains an image of a vicinity of a beam waist of laser light  5 . Image pick-up device  108  receives white light  6  radiated from illumination light source  102  to irradiate the liquid and having passed through the liquid, and accordingly, image pick-up device  108  corresponds to a “photoreceiver” according to the present invention. Image pick-up device  108  is implemented for example as a video camera equipped with a charge coupled device (CCD) image sensor. Note that image pick-up device  108  may pick up a moving image or a static image. 
     The  FIG. 4  configuration provides objective lens  103  positionally fixed. Adjustment mechanism  112  adjusts an xyz-axis stage  114  (see  FIG. 5 ) positionally in the x, y and z directions with kit  20  mounted thereon. Adjustment mechanism  112  can be implemented for example as a focusing handle attached to a microscope. The position of kit  20  relative to objective lens  103  is thus adjusted. Note that adjustment mechanism  112  is not limited to any particular configuration. Furthermore, adjustment mechanism  112  may adjust the position of objective lens  103  relative to kit  20  fixed. 
     A laser displacement meter  109  can be used to adjust the position of the beam waist of laser light  5 . Furthermore, laser displacement meter  109  can also be used in measuring the dispersion liquid of sample  30  in thickness and determining the position of the gas-liquid interface. Laser displacement meter  109  for example measures a vertical distance between laser displacement meter  109  and kit  20  and also measures horizontal displacement of kit  20 . Adjustment mechanism  112  may refer to a resultant measurement that is provided by laser displacement meter  109  to adjust the position of the xyz-axis stage. Note that laser displacement meter  109  is not an essential component. 
     Computation unit  106  is implemented as a microcomputer or a personal computer or the like, for example. Computation unit  106  receives a signal from image pick-up device  108  (e.g., a signal indicating a moving image obtained through image pick-up device  108 ). Computation unit  106  detects target DNA  18  based on the signal received from image pick-up device  108 . 
       FIG. 5  is an enlarged view of a configuration in a vicinity of kit  20  of detection device  100  shown in  FIG. 4 .  FIG. 5(A)  is a diagram showing a configuration of a vicinity of a kit  20 .  FIG. 5(B)  is a diagram showing an optical system of objective lens  103  more specifically. With reference to  FIG. 5(A) , kit  20  includes a substrate  21 . Kit  20  may include a liquid level guide  24  provided on substrate  21 . 
     Substrate  21  receives sample  30  dropped thereon having a specimen and gold nanoparticles  11 ,  12  introduced therein. Substrate  21  can be made of a material transparent to white light. Preferably, substrate  21  is for example made of glass, quartz or a similar material that does not present anisotropy to polarized light. 
     Liquid level guide  24  indicates where sample  30  should be dropped. Liquid level guide  24  is determined in geometry, as appropriate, depending on the volume of sample  30  dropped, the level of the gas-liquid interface to be formed, as measured from substrate  21  (i.e., a distance in the z direction from the substrate to the gas-liquid interface), and the like. Liquid level guide  24  can be made for example of a water-repellent material such as polymer film. Kit  20  may for example be a commercially available glass bottomed dish. Thus, kit  20  is not limited to the configuration shown in  FIG. 5(A) . 
     In this embodiment, the distance between objective lens  103  and sample  30  is determined so that laser light  5  has a beam waist in the liquid. Laser light  5  has the beam waist formed at the position of a focal point of objective lens  103 . That is, objective lens  103  and sample  30  have their relative positions adjusted so that objective lens  103  has its focal point positioned in the liquid. 
     D 2  represents a distance between an upper surface  21   a  of substrate  21  and the focal point of objective lens  103 . Distance D 2  is adjusted to position the focal point of objective lens  103  in the liquid. Distance D 2  can be adjusted from a focal length F of objective lens  103 , a thickness T of substrate  21 , and a distance D 1  between a major surface  103   a  of objective lens  103  and an upper surface  114   a  of xyz-axis stage  114  (or a lower surface  21   b  of substrate  21 ), for example as follows: 
     Focal length F is known from a value of a specification of objective lens  103 . Furthermore, thickness T of substrate  21  is known from a value of a specification of substrate  21  (e.g., a glass bottomed dish). 
     Adjustment mechanism  112  includes a control unit (not shown), which has a function to move xyz-axis stage  114  to a prescribed reference position for example in response to an initialization operation done by the user. When xyz-axis stage  114  is in the reference position, distance D 1  has a reference value previously stored by the control unit. When the control unit operates in response to the user&#39;s operation to adjust the position of xyz-axis stage  114  in the z direction, it calculates distance D 1 , as adjusted, from a displacement of xyz-axis stage  114  from the reference position of xyz-axis stage  114  in the z direction. 
     Objective lens  103  has focal length F equal to the sum of distance D 1 , thickness T of substrate  21 , and distance D 2  (F=D 1 +T+D 2 ). Distance D 2  is represented as D 2 =F−D 1 −T, in other words. As has been set forth above, focal length F and thickness T of substrate  21  have known values. Furthermore, distance D 1  is calculated by the control unit of adjustment mechanism  112 . The adjustment mechanism  112  control unit can thus calculate distance D 2 . 
     With reference to  FIG. 5(B) , how distance D 2  is calculated will more specifically be described by indicating a specific example. Objective lens  103  can for example be Nikon CFI Plan Fluor 100XH oil (observation magnification: 100×, working distance: 0.16 mm, and focal length: 2 mm) 
     When objective lens  103  and substrate  21  have an upper surface  103   b  and lower surface  21   b , respectively, with a distance therebetween set to 160 μm, objective lens  103  has a focal point matched to the substrate  21  upper surface  21   a . This distance is referred to as a working distance (WD). Immersion oil  115  is introduced to fill a gap between upper surface  103   b  of objective lens  103  and lower surface  21   b  of substrate  21 . 
     Objective lens  103  is movable from this state along the z axis to a position immediately before it has upper surface  103   b  in contact with lower surface  21   b  of substrate  21 . That is, objective lens  103  can move a distance of 160 μm or smaller in the z direction. Accordingly, objective lens  103  has a focal point in the z direction in a range (i.e., distance D 2  has a range) of 0 mm to 160 μm as measured from upper surface  21   a  of substrate  21 . Note that sample  30  has an index of refraction different from that of air (an index of refraction of 1.33 for a dispersion medium of water or phosphate buffer), and accordingly, it is desirable to adjust focus while considering the index of refraction of sample  30 . 
     Furthermore, the observation system&#39;s magnification is calculated from a value of a specification of a focal length of an imaging lens (not shown) incorporated into the body of a microscope (not shown), as follows: magnification=the imaging lens&#39;s focal length/the objective lens&#39;s focal length=200 mm/2 mm=100 times. 
     When distance D 3  from gas-liquid interface  31  to upper surface  21   a  of substrate  21  has larger values, the observation system&#39;s focus position is more offset from the position of the focal point of objective lens  103 . A focused image can be obtained by setting objective lens  103  to have a focal point positioned in the horizontal direction (or the y direction) for example at an end of gas-liquid interface  31 , i.e., at gas-liquid interface  31  in a vicinity of liquid level guide  24 . As an example, when sample  30  has a volume of 15 μL, objective lens  103  desirably has a focal point in the horizontal direction at a position for example of 50 μm or smaller in the y direction with reference to liquid level guide  24 . 
     Furthermore, it is preferable that distance D 2  is set for example to 20 μm or smaller. Focal length F is for example 2 mm and thickness T is for example 0.17 mm. Accordingly, when distance D 1  has a reference value D 1 α and distance D 1  is displaced from reference value D 1 α by an amount of D 1 β, then, distance D 2 =F−T−(D 1 α+D 1 β)=2,000−170−(D 1 α+D 1 β). In other words, distance D 2  of 20 μm or smaller can be provided by setting D 1 =(D 1 α+D 1 β) to be 1810 μm or larger. 
     Note that in the configuration shown in  FIG. 4  and  FIG. 5 , sample  30  is dropped on substrate  21  placed in a horizontal plane (i.e., the xy plane). Furthermore, objective lens  103  is arranged vertically under substrate  21  (or in the z direction thereunder). However, the surface in which the substrate is placed is not limited to a precisely horizontal plane, and may have inclination relative to the horizontal plane. Furthermore, the objective lens may be arranged vertically over or under the substrate. For example, the objective lens may be arranged vertically over the substrate that is placed in a horizontal plane. Thus, the laser light is radiated vertically downward (i.e., from the same side as the gas-liquid interface with respect to the substrate). 
       FIG. 6  is a schematic diagram for illustrating how gold nanoparticles  11 ,  12  aggregate in a vicinity of a beam waist of laser light  5  shown in  FIG. 5 .  FIG. 6(A)  shows gold nanoparticles  11  and  12  before they aggregate.  FIG. 6(B)  shows gold nanoparticles  11  and  12  after they aggregate. 
     With reference to  FIG. 6(A) , when the gas-liquid interface is irradiated with laser light  5 , gold nanoparticles  11  and  12  gather at the gas-liquid interface. This allows gold nanoparticles  11  and  12  to have an increased density locally larger in a vicinity of the beam waist than at the other locations. The beam waist has a beam diameter for example of approximately several μm. 
     Then, with reference to  FIG. 6(B) , when target DNA  18  is present around gold nanoparticles  11  and  12 , probe DNA  13  and target DNA  18  hybridize together and so do probe DNA  14  and target DNA  18 . Target DNA  18  has a length for example on an order of nanometers (e.g., from several nanometers to several tens nanometers). Note that, as has been set forth above, laser light  5  has a wavelength for example of 1064 nm. Accordingly, gold nanoparticles  11 ,  12  have therebetween a distance fixed on a scale equal to or smaller than the wavelength of laser light  5  and equal to or smaller than visible light&#39;s wavelength. 
     Probe DNAs  13 ,  14  present on the surfaces of gold nanoparticles  11 ,  12  having a fixed interparticle distance further hybridize with other neighboring target DNA  18 . DNA hybridization increases the assembly of gold nanoparticles  11 ,  12  in size, which in turn provides an increased probability of target DNA  18  being present in a vicinity of the assembly and hence further helps DNA hybridization to arise. The assembly of gold nanoparticles  11 ,  12  increased in size thus allows DNA hybridization to arise more frequently. In other words, the present embodiment allows light irradiation to accelerate forming a gold nanoparticle assembly. As a result, a gold nanoparticle assembly of gold nanoparticles  11 ,  12  densely aggregated together is formed in a short period of time. 
       FIG. 7  is a flowchart for illustrating a method for detecting target DNA  18  according to the first embodiment of the present invention. With reference to  FIG. 4 ,  FIG. 5  and  FIG. 7 , in step S 1 , gold nanoparticles  11  and  12  modified with probe DNAs  13  and  14 , respectively, are introduced into sample  30  containing a specimen. 
     In step S 2 , adjustment mechanism  112  adjusts the position of sample  30  relative to the focal point of objective lens  103 . As has been set forth above, objective lens  103  preferably has a focal point in the liquid in a vicinity of gas-liquid interface  31 . As in this embodiment, when sample  30  has a minute volume (for example on the order of microliters), objective lens  103  has a focal point adjusted to have a position closer to gas-liquid interface  31  than a midpoint M between the upper surface of substrate  21  and gas-liquid interface  31  on an optical axis L of laser light  5 . The distance between the focal point of objective lens  103  and gas-liquid interface  31  can be adjusted for example as follows. 
     The control unit of adjustment mechanism  112  obtains an image of a droplet of sample  30  with a camera (not shown), and obtains from the image a level D 3  of gas-liquid interface  31  as measured from substrate  21 . The region surrounded by liquid level guide  24  has a fixed area, and accordingly, there is a correlation between the volume (or amount dropped) of sample  30  and level D 3  of gas-liquid interface  31 . The control unit stores this correlation previously for example as a table. Level D 3  of gas-liquid interface  31  can be obtained from this table and an amount of sample  30  actually dropped. Alternatively, the control unit may obtain an image of sample  30  for each measurement and obtain level D 3  of gas-liquid interface  31  therefrom. 
     As has been described with reference to  FIG. 5 , distance D 2  from upper surface  21   a  of substrate  21  to the focal point can be obtained based on focal length F of objective lens  103 , thickness T of substrate  21 , and distance D 1  between major surface  103   a  of objective lens  103  and lower surface  21   b  of substrate  21 . Accordingly, level D 3  of gas-liquid interface  31  obtained as described above allows distance D 4  between gas-liquid interface  31  and the focal point to be calculated. 
     Note that when the region surrounded by liquid level guide  24  is for example a circle of a radius R, it is not necessary to obtain an image of sample  30 . In that case, sample  30  dropped can be geometrically approximated to a semi-spheroid. Accordingly, when sample  30  has a volume V and a maximum height H (i.e., a distance at the center of the above region between the upper surface of substrate  21  and gas-liquid interface  31  along the optical axis of laser light  5 ), a relationship of V=2πR 2 H/3 is established. That is, maximum height H is equal to (3/2)×V/(πR 2 ). Accordingly, the maximum height of the gas-liquid interface at the center of the region can be calculated from the amount of the sample dropped. For example, when V=15 μL, and a droplet on the substrate has a radius of 2.5 mm, maximum height H can be estimated to be equal to 1.15 mm. The estimation allows the droplet&#39;s geometry and size to be modeled and thus referenced in determining where the laser light should be radiated. 
     In step S 3 , kit  20  is irradiated with laser light  5  output from optical trapping light source  101 . When sample  30  includes target DNA  18 , and light irradiation starts and then a period of time has elapsed, gold nanoparticle assembly  10  is formed. 
     In step S 4 , image pick-up device  108  obtains an image of sample  30 . Note that when image pick-up device  108  provides a moving image, image pick-up device  108  may start obtaining the image in step S 3  before light irradiation starts. 
     In step S 5 , computation unit  106  processes the image provided from image pick-up device  108  and, from a result of the processing, determines whether target DNA  18  is present or absent. The image can be processed by a variety of known signal processing techniques. 
     For example, pattern recognition technology can be employed when what feature in geometry the gold nanoparticle assembly has with target DNA  18  present is previously known. As will be indicated hereinafter, a gold nanoparticle assembly under some measurement condition(s) is formed in a network. Computation unit  106  employs pattern recognition technology to extract a feature of a pattern of the network. Once the feature of the pattern has been extracted, it is determined that target DNA  18  is present. Alternatively, for example, whether target DNA  18  is present or absent can be determined based on the area of a portion of the image that has a deeper color resulting from transmitted light reduced as a gold nanoparticle assembly is formed. 
     One example of a result of having detected target DNA  18  will now be described with reference to an image obtained by image pick-up device  108 . Sample  30  was prepared in the following method: 
     Initially, a dispersion liquid containing gold nanoparticle  11  modified with probe DNA  13  (hereinafter referred to as a dispersion liquid A) and a dispersion liquid containing gold nanoparticle  12  modified with probe DNA  14  (hereinafter referred to as a dispersion liquid B) were prepared independently. Dispersion liquids A and B contain gold nanoparticles at a concentration of 5.0 nM. 
     Gold nanoparticle  11  in dispersion liquid A of the concentration of 5.0 nM and gold nanoparticle  12  in dispersion liquid B of the concentration of 5.0 nM both have an average interparticle distance (or center-to-center distance) calculated to be 0.693 μm. 
     Furthermore, mixed liquid of equal amounts of dispersion liquid A, dispersion liquid B, and dispersion liquid containing an analyte will contain gold nanoparticles  11  and  12  each at a concentration of 5.0/3=1.66 nM. Accordingly, the mixed liquid of equal amounts of dispersion liquids contains gold nanoparticles  11  with an average interparticle distance calculated to be 0.999 μm and gold nanoparticles  12  with an average interparticle distance calculated to be 0.999 μm. 
     Furthermore, if the mixed liquid of equal amounts of dispersion liquids has gold nanoparticles  11  and gold nanoparticles  12  uniformly mixed together, and gold nanoparticles  11  and  12  are not distinguished from each other, then the gold nanoparticles will have a concentration of 1.66+1.66=3.33 nM. Accordingly the mixed liquid of equal amounts of dispersion liquids contains the gold nanoparticles with an average interparticle distance calculated to be 0.793 μm. 
     Note that it is known that DNA has adjacent bases with a distance of 0.34 nm therebetween. The present embodiment employs probe DNAs  13  and  14  each having 12 bases, and accordingly, probe DNAs  13  and  14  have a size (or length) calculated to be about 0.34×12=4.08 nm. Furthermore, target DNA  18  has 24 bases, and accordingly, target DNA  18  has a size calculated to be about 0.34×24=8.16 nm. Accordingly, preferably, before probe DNAs  13  and  14  and target DNA  18  hybridize together, the gold nanoparticles are dispersed in the liquid such that the gold nanoparticles have an averaged surface-to-surface distance larger than the sum of the lengths of probe DNA  13 , probe DNA  14  and target DNA  18 . 
     The gold nanoparticles&#39; averaged surface-to-surface distance is calculated as the gold nanoparticles&#39; average interparticle distance (or center-to-center distance) minus the gold nanoparticle&#39;s diameter. The above average interparticle distance of 0.793 μm minus the gold nanoparticle&#39;s diameter of 30 nm will be 0.790 μm. Thus the gold nanoparticles have an averaged surface-to-surface distance larger than the sum of the lengths of probe DNA  13 , probe DNA  14  and target DNA  18 , i.e., 4.08+4.08+8.16=16.32 nm, and thus satisfying the condition set forth above. 
     Then, 100 μM of an undiluted solution of target DNA and 100 μM of an undiluted solution of a mismatched DNA were prepared as an undiluted solution of sample  30 . Target DNA  18  is a complementary DNA having a base sequence complementary to probe DNAs  13  and  14 , as has been described with reference to  FIG. 3 . A mismatched DNA is a DNA which has a mismatched base and accordingly does not hybridize with probe DNA  13  or  14 . The undiluted solution of the complementary DNA was diluted with a phosphate buffer 10,000-fold to provide a 10 nM diluted dispersion liquid. On the other hand, the undiluted solution of the mismatched DNA was diluted with a phosphate buffer 100-fold to provide a 1 μM diluted dispersion liquid. That is, the diluted dispersion liquid of the mismatched DNA has a concentration 100 times that of the diluted dispersion liquid of the complementary DNA. 
     The above dispersion liquids were used to prepare two samples for comparison. One sample contains 5 μL of dispersion liquid A, 5 μL of dispersion liquid B, and 5 μL of the diluted dispersion liquid of the complementary DNA. The other sample contains 5 μL of dispersion liquid A, 5 μL of dispersion liquid B, and 5 μL of the diluted dispersion liquid of the mismatched DNA. In other words, each sample has a volume of 15 μL. These samples were dropped on substrate  21 . 
       FIG. 8  to  FIG. 17  show images of the samples in the horizontal direction (i.e., the x and y directions shown in  FIG. 4 ). Note that these images do not show liquid level guide  24  (See  FIG. 5 ). 
       FIG. 8(A)  shows an image of the sample containing the diluted dispersion liquid of the complementary DNA (concentration: 10 nM) naturally dried for 1 hour without undergoing light irradiation. With reference to  FIG. 8(A) , the complementary DNA and the probe DNAs hybridize together to form a network-like aggregate of gold nanoparticles. 
     In contrast,  FIG. 8(B)  shows an image of the sample containing the diluted dispersion liquid of the mismatched DNA (concentration: 1 μM) naturally dried for 1 hour without undergoing light irradiation, as observed on the substrate. With reference to  FIG. 8(B) , when the mismatched DNA and the probe DNAs do not hybridize together, a ball-like aggregate of approximately several μm was observed. As can be seen from  FIG. 8(A)  and  FIG. 8(B) , presence/absence of DNA hybridization presents a clear difference in geometry between aggregates observed after the samples are naturally dried. 
       FIG. 9(A)  is an image of the diluted dispersion liquid of the complementary DNA (concentration: 10 nM) before light irradiation in a vicinity of a portion to be exposed to a beam waist.  FIG. 9(B)  is an image of the diluted dispersion liquid of the mismatched DNA (concentration: 1 μM) before light irradiation in a vicinity of a portion to be exposed to a beam waist. 
     With reference to  FIG. 9(A)  and  FIG. 9(B) , image pick-up device  108  obtains images of a region having a size of 69 μm×52 μm. Each image has a lower portion having a dark color, which is denoted as L, which corresponds to a liquid. Each image has an upper portion having a light color, which is denoted as A, which corresponds to a gas. A white portion between the liquid and the gas, which is denoted as I, is a gas-liquid interface. Before laser light  5  is radiated, gold nanoparticle assembly  10  is not observed in any of the diluted dispersion liquid of the complementary DNA or the diluted dispersion liquid of the mismatched DNA. 
     The above diluted dispersion liquids each had a vicinity of its gas-liquid interface irradiated with laser light  5  for a period of 2 minutes and 40 seconds. Optical trapping light source  101  outputs laser light  5  having an intensity set to 0.2 W. 
       FIG. 10(A)  is an image of the diluted dispersion liquid of the complementary DNA (concentration: 10 nM) on the substrate after light irradiation, and  FIG. 10(B)  is an image of the diluted dispersion liquid of the mismatched DNA (concentration: 1 μM) on the substrate after light irradiation.  FIG. 10(A)  and  FIG. 10(B)  are compared with  FIG. 9(A)  and  FIG. 9(B) , respectively. Each image presents at the center a circle, which schematically represents the position of the beam waist of laser light  5 . The beam waist, as seen in the vertical direction (or the z direction), is positioned 20 μm above substrate  21 . 
     Initially, with reference to  FIG. 10(A) , in the diluted dispersion liquid of the complementary DNA, gold nanoparticle assembly  10  is formed in a vicinity of the beam waist. 
     On the other hand, with reference to  FIG. 10(B) , in the diluted dispersion liquid of the mismatched DNA, there is no gold nanoparticle assembly  10  clearly observed. Thus, while the diluted dispersion liquid of the mismatched DNA has a concentration 100 times that of the diluted dispersion liquid of the complementary DNA, gold nanoparticle assembly  10  is formed only when the complementary DNA is introduced. 
     The same samples were used and the beam waist&#39;s position is changed, and their images were obtained in a vicinity of the beam waist. The beam waist, as seen in the vertical direction (or the z direction), is positioned 15 μm above substrate  21 . 
       FIG. 11(A)  is an image of the diluted dispersion liquid of the complementary DNA (concentration: 10 nM) before light irradiation in a vicinity of a portion to be exposed to the differently positioned beam waist.  FIG. 11(B)  is an image of the diluted dispersion liquid of the mismatched DNA (concentration: 1 μM) in a vicinity of the differently positioned beam waist.  FIG. 11(A)  and  FIG. 11(B)  are compared with  FIG. 9(A)  and  FIG. 9(B) , respectively. With reference to  FIG. 11(A)  and  FIG. 11(B) , in  FIG. 11 , as well as  FIG. 9 , before light irradiation there is no gold nanoparticle assembly  10  clearly observed. 
       FIG. 12(A)  is an image of the diluted dispersion liquid of the complementary DNA (concentration: 10 nM) on the substrate after light irradiation for the differently positioned beam waist.  FIG. 12(B)  is an image of the diluted dispersion liquid of the mismatched DNA (concentration: 1 μM) on the substrate.  FIG. 12(A)  and  FIG. 12(B)  are compared with  FIG. 10(A)  and  FIG. 10(B) , respectively. 
     With reference to  FIG. 12(A) , after light irradiation, gold nanoparticle assembly  10  is formed in a large region of 100 μm×100 μm or larger. When  FIG. 12(A)  is compared with  FIG. 10(A) , the former, which is the same sample as the latter, nonetheless presents gold nanoparticle assembly  10  larger in size. This may be because the sample&#39;s dispersion medium has evaporated as time elapses, and gold nanoparticles  11  and  12  and the complementary DNA accordingly have an increased concentration. Note that it is believed that gold nanoparticle assembly  10  in a vicinity of the beam waist was blown away by the pressure of laser light  5 . 
     On the other hand, in  FIG. 12(B) , as well as  FIG. 10(B) , the diluted dispersion liquid of the mismatched DNA does not have any gold nanoparticle assembly  10  clearly observed. 
     In the above detected results, sample  30  dropped on substrate  21  contains the complementary DNA in an amount of substance of 10 nM×5 μL=50 fmol (1 fmol=10 −15  mol). Thus according to the present embodiment it can be seen that target DNA  18  of a trace amount of about 50 fmol is detectable. 
     The above amount of substance is an amount of substance of the complementary DNA that is contained in the entirety the sample  30  dropped. Accordingly, image pick-up device  108  obtains an image in a region containing the complementary DNA in an amount of substance smaller than 50 fmol. Thus it can be estimated that target DNA  18  of a trace amount smaller than 50 fmol is detectable. 
     Furthermore, according to  FIG. 10(A)  or  FIG. 12(A) , after the light irradiation in two minutes and 40 seconds at the latest, it is clearly confirmed that gold nanoparticle assembly  10  is present. However, if simply confirming whether gold nanoparticle assembly  10  has been formed is the purpose, a period of time for which radiation of laser light  5  is required may be shorter than two minutes and 40 seconds. For example, an experiment done by the present inventors for verification has indicated that even one minute or shorter of light irradiation allows a gold nanoparticle assembly to be confirmed. Thus it can be estimated that target DNA  18  of a trace amount smaller than 50 fmol is detectable in a short period of time within one minute. 
     Note that laser light  5  has an intensity of 0.2 W, which is one example of a measurement condition in the present embodiment, and laser light  5  is not limited to that intensity. For laser light intensity, there is an appropriate range depending on the metallic nanoparticle&#39;s type and concentration, the analyte&#39;s type and concentration and the host molecule&#39;s type and concentration, and the like. That is, a light intensity lower than the appropriate range&#39;s lower limit value cannot assemble the metallic nanoparticles in a vicinity of the beam waist. In contrast, a light intensity higher than the appropriate range&#39;s upper limit value may affect the analyte (e.g., heat it and thus have an effect to break a DNA bond). Accordingly, the laser light&#39;s optimal intensity is determined based on an experiment, as appropriate. 
     Then the diluted dispersion liquid of the complementary DNA is changed in concentration and an image thereof was obtained in a vicinity of the beam waist. The above-mentioned undiluted solution of the complementary DNA was diluted with a phosphate buffer 1,000,000-fold to provide a 10 pM diluted dispersion liquid. In other words, this diluted dispersion liquid contains the complementary DNA in a concentration of 1/100 of that of the diluted dispersion liquid used in connection with  FIG. 9  to  FIG. 12 . The samples are all equal in volume (i.e., 15 μL). Thus, the sample indicating a result of detection therefrom below contains the complementary DNA in an amount of substance of 50 fmol× 1/100=500 amol (1 amol=10 −18  mol). 
       FIG. 13  is an image of the diluted dispersion liquid of the complementary DNA that has a different concentration on a substrate after light irradiation. With reference to  FIG. 13  the beam waist has the same position as that of the beam waist shown in  FIG. 12(A)  (i.e., 15 μm above substrate  21  as seen in the z direction). Light irradiation is also provided for the same period of time as that for  FIG. 12(A) . 
     The  FIG. 13  gold nanoparticle assembly is smaller in size than the  FIG. 12(A)  gold nanoparticle assembly. This result shows that the gold nanoparticle assembly varies in size with in how much amount of substance a sample contains the complementary DNA. 
       FIG. 14  presents successive photographic images of how a gas-liquid interface of the diluted dispersion liquid of the mismatched DNA (in a vicinity of the beam waist) after light irradiation starts varies with time.  FIG. 15  presents successive photographic images of how a gas-liquid interface of the diluted dispersion liquid of the complementary DNA (in a vicinity of the beam waist) after light irradiation starts varies with time.  FIG. 16  presents successive photographic images of a gas-liquid interface of the diluted dispersion liquid of the complementary DNA (in a vicinity of the beam waist) with a concentration of 100 pM.  FIG. 17  presents successive photographic images of a gas-liquid interface of the diluted dispersion liquid of the complementary DNA (in a vicinity of the beam waist) with a concentration of 1 pM. The  FIGS. 14-17  images are obtained for every 6 seconds with radiation of laser light  5  started at a time of 0 second. Furthermore, the positions respectively of liquid (L), gas (A), and gas-liquid interface (I) are not shown as they are equivalent to those shown in  FIG. 9  to  FIG. 13 . Each sample has a volume of 15 μL. 
     Initially, with reference to  FIG. 14 , the aforementioned undiluted solution of the mismatched DNA was diluted with a phosphate buffer 100-fold to prepare a 1 μM diluted dispersion liquid. As the diluted dispersion liquid is dropped in a volume of 5 μL, sample  30  contains the mismatched DNA in an amount of substance of 1 μM×5 μL=5 pmol (1 pmol=10 −12  mol) 
     The sample containing the diluted dispersion liquid of the mismatched DNA does not present gold nanoparticle assembly  10  even after light irradiation. Note that an image obtained after 60 seconds shows a gas-liquid interface with bubble. 
     Then, with reference to  FIG. 15 , the undiluted solution of the complementary DNA was diluted with a phosphate buffer 10,000-fold to prepare a 10 nM diluted dispersion liquid. The sample contains the complementary DNA in an amount of substance of 10 nM×5 μL=50 fmol. That is, the complementary DNA has an amount of substance of 1/100 of that of the mismatched DNA contained in the sample shown in  FIG. 14 . Furthermore, the complementary DNA has a concentration of 50 fmol/15 μL=3.3 nM. 
     A sample containing the complementary DNA in an amount of substance equal to that of the mismatched DNA contained in the  FIG. 14  sample (i.e., a sample prepared by diluting the undiluted solution of the complementary DNA 100-fold) presents a gold nanoparticle assembly spontaneously formed with or without light irradiation. On the other hand, when the  FIG. 15  sample diluted 10,000-fold is not irradiated with light, the gold nanoparticle assembly is less spontaneously formed. However, light irradiation and an elapse of at least a period of 6 seconds allow a gold nanoparticle assembly to be observed in a vicinity of the gas-liquid interface. It can be seen that thereafter the gold nanoparticle assembly rapidly grows as time elapses. 
     With reference to  FIG. 16 , the undiluted solution of the complementary DNA was diluted with a phosphate buffer 1,000,000-fold to prepare a 100 pM diluted dispersion liquid. The sample contains the complementary DNA in an amount of substance of 100 pM×5 μL=500 amol. That is, the complementary DNA has an amount of substance of 1/10,000 of that of the mismatched DNA contained in the sample shown in  FIG. 14 . Furthermore, the complementary DNA has a concentration of 500 amol/15 μL=33 pM. The beam waist is positioned in the liquid horizontally (or in the x direction) inner than the gas-liquid interface by 13 μm and vertically (or in the z direction) above substrate  21  by 15 μm. 
     This diluted dispersion liquid of the complementary DNA also allows a gold nanoparticle assembly to be observed in a vicinity of the gas-liquid interface after at least a period of 6 seconds elapses. However, the gold nanoparticle assembly grows at a rate slower than that in  FIG. 15 . 
     With reference to  FIG. 17 , the undiluted solution of the complementary DNA was diluted with a phosphate buffer 100,000,000-fold to prepare a 1 pM diluted dispersion liquid. The sample contains the complementary DNA in an amount of substance of 1 pM×5 μL=5 amol. That is, the complementary DNA has an amount of substance of 1/1,000,000 of that of the mismatched DNA contained in the sample shown in  FIG. 14 . Furthermore, the complementary DNA has a concentration of 5 amol/15 μL=0.33 pM. The beam waist is positioned in the liquid horizontally (or in the x direction) inner than the gas-liquid interface by 3 μm and vertically (or in the z direction) above substrate  21  by 5 μm. 
     This diluted dispersion liquid of the complementary DNA also allows a gold nanoparticle assembly to be observed in a vicinity of the gas-liquid interface after a period of 6 seconds elapses. Thereafter, as time elapses, the presence of the gold nanoparticle assembly becomes clearer. From this detection result it can be seen that the present embodiment allows even target DNA  18  of a trace amount of about 5 amol to be also detectable. 
     As can be seen from  FIG. 14  to  FIG. 17 , while the sample containing the mismatched DNA does not present any change even through light irradiation, the sample containing the complementary DNA, even in an amount of substance of 50 fmol to 5 amol, presents a gold nanoparticle assembly through light irradiation. Thus a trace amount of target DNA  18  can specifically be detected. Furthermore, the gold nanoparticle assembly is formed at the beam waist located in a vicinity of the gas-liquid interface and thereafter grows as time elapses. It can be seen that the gold nanoparticle assembly&#39;s size and growth rate depend on the amount of substance of target DNA  18 . 
     A trace amount of an analyte can be detected by other techniques including for example a gene detection method by polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), fluorescent staining flow cytometry or the like. However, for example, PCR requires repeating a cycle of amplifying DNA, and thus generally requires a detection time of several hours. ELISA and fluorescent staining flow cytometry also require a detection time of several hours. 
     In contrast, according to the present embodiment, whether a gold nanoparticle assembly is present can rapidly be confirmed within a short time of several seconds to 1 minute. Accordingly, the present embodiment can reduce the detection time to be significantly shorter than PCR or conventional methods for detecting a trace amount of an analyte. 
     In particular, if it is assumed in the  FIG. 17  result that the complementary strands of DNA are dispersed uniformly in sample  30  before light irradiation starts, then, a region that is imaged (a region of 69 μm×52 μm) contains 12 complementary strands of DNA, i.e., approximately 0.02 amol (1 zmol=10 −21  mol). Accordingly, the present embodiment suggests a possibility of allowing an analyte of a significantly trace amount of an extent of sub-zepto mole to be detectable. Furthermore, if the region to be observed is previously determined, a possibility is indicated that the detection time can be shortened to about several seconds. 
     In the present embodiment one factor allowing a significantly reduced detection time is having adjusted the position of the beam waist to be in a vicinity of the gas-liquid interface of the sample. The sample&#39;s dispersion medium evaporates from the gas-liquid interface. This increases the density of the gold nanoparticles and target DNA  18  in a vicinity of the gas-liquid interface to be larger than that in the bulk. This provides an increased probability of the gold nanoparticles encountering target DNA  18  in the vicinity of the gas-liquid interface and thus facilitates DNA hybridization. 
     Another factor allowing a significantly reduced target DNA  18  detection time may be an effect of a convection flow generated as the laser light heats the dispersion medium around the beam waist. The convection flow allows a further increased probability of the gold nanoparticles encountering target DNA  18 . Actually, a moving image obtained by the image pick-up device allows a convection flow to be observed. 
     For example, fluorescent staining flow cytometry or a similar technique using a fluorescent material requires a skillful engineer to subject a specimen to an advanced pretreatment. Furthermore, it also employs expensive reagents and an expensive detection device. 
     The present embodiment does not require fluorescent labeling, and can thus implement a so-called label-free detection. Furthermore, when the present embodiment is compared with fluorochrome staining, the former facilitates operating a detection device and preparing a regent and thus does not require a skilled engineer. Furthermore, the present embodiment allows the detection device to be simply configured and an inexpensive reagent to be used. Thus the present embodiment can provide the detection device at low cost. 
     While the present embodiment has been described for detection of DNA, the present invention allows an antigen to be detected via a gold nanoparticle modified with an antibody, rather than a probe DNA. As one example, albumin, which is a type of antigen, can serve as an analyte. In that case, the gold nanoparticle is modified with immunoglobulin (IgE), which is an antibody specifically compositing with albumin. 
     Albumin has a size (or a long axis) of about 10 nm (for example, bovine serum albumin has a size of 6.9 nm). Furthermore, an antibody typically has a size (or length) of 10-15 nm, and IgE has a size of about 10 nm. Accordingly, a sum of the antigen&#39;s size and twice the antibody&#39;s size is estimated to be about 30 nm. On the other hand, as has been described above, the averaged surface-to-surface distance of gold nanoparticles in a dispersion liquid is calculated based on the gold nanoparticles&#39; concentration, and when the gold nanoparticles have a concentration equal to or smaller than 7.7 μM, the gold nanoparticles will have an averaged surface-to-surface distance of 30 nm or larger. In other words, the gold nanoparticles having the concentration of equal to or smaller than 7.7 μM in a dispersion liquid are dispersed in the dispersion liquid with an averaged surface-to-surface distance larger than a sum of the antigen&#39;s size and twice the antibody&#39;s size. 
     As one example, when a liquid mixture of a gold nanoparticle dispersion liquid and an albumin dispersion liquid contains gold nanoparticles in a concentration of 3.33 nM, then, the gold nanoparticles before forming a gold nanoparticle assembly have an averaged surface-to-surface distance represented by an average interparticle distance (or center-to-center distance) of 0.793 μm minus the gold nanoparticle&#39;s diameter of 30 nm, i.e., 0.790 μm, which is larger than 30 nm. It can thus be said that the gold nanoparticles are dispersed in the dispersion liquid with an averaged surface-to-surface distance larger than a sum of albumin&#39;s size and twice IgE&#39;s size. 
     Second Embodiment 
     The first embodiment employs an image of a sample to determine whether an analyte is present. However, the information for determining whether the analyte is present is not limited to the image. The present embodiment employs a sample&#39;s spectrum to determine whether an analyte is present. 
     A metallic nanoparticle in the second embodiment is a metallic nanoparticle that can cause localized surface plasmon resonance. For example, when the gold nanoparticle is irradiated with light of the visible to near-infrared ranges, localized surface plasmon resonance is induced on a surface of the gold nanoparticle. Any metallic nanoparticle other than the gold nanoparticle that can cause localized surface plasmon resonance is applicable to the present invention. Another such exemplary metallic nanoparticle is a silver nanoparticle, for example. 
     Gold nanoparticles irradiated with light and thus arranged adjacent to each other to a scale smaller than light&#39;s wavelength are irradiated with white light and their scattering spectrum is calculated.  FIG. 18  shows a result of a calculation of how the scattering spectrum varies depending on the number N of adjacent gold nanoparticles. With reference to  FIG. 18 , the axis of ordinate represents intensity of scattered light per gold nanoparticle. A scattering spectrum&#39;s peak wavelength and peak width and an absorption spectrum&#39;s peak wavelength and peak width are substantially the same. 
     This calculation is done for number N having different values of 1, 2, 4 and 8, and presents a result indicating that number N having a larger value allows the scattering spectrum to have a peak wavelength more red-shifted than number N having a smaller value. Furthermore, number N having a larger value presents a peak wavelength range (e.g., a wavelength range of full width at half maximum) broader than number N having a smaller value. These optical response variations can be utilized to determine whether target DNA  18  is present. 
       FIG. 19  represents how an absorption spectrum presented by gold nanoparticles  11 ,  12  varies between before and after their aggregation. With reference to  FIG. 19 , when a liquid having gold nanoparticles  11 ,  12  dispersed therein in a concentration of an extent is irradiated with white light and its absorption spectrum is measured, the absorption spectrum before DNA hybridization has a peak wavelength included in a wavelength range of green (e.g., a wavelength range of 495-570 nm). Accordingly, the color of the liquid containing gold nanoparticles  11  and  12  turns into the complementary color of green, i.e., red. 
     In contrast, after DNA hybridization, gold nanoparticle assembly  10  is formed, which increases number N of gold nanoparticles present in a vicinity of the beam waist of laser light  5 . Accordingly, the absorption spectrum has the peak wavelength red-shifted and also broadened in range. The absorption spectrum after DNA hybridization has the peak wavelength in a wavelength range of yellow to orange color (e.g., a wavelength range of 570-620 nm). Accordingly, the color of the liquid turns into the complementary color of yellow to orange color, i.e., blue to bluish-purple color. Accordingly, spectrally dispersing the liquid containing gold nanoparticles  11  and  12  allows gold nanoparticle assembly  10  to be detected. That is, whether the liquid contains target DNA  18  can be determined. 
       FIG. 20  schematically shows a configuration of a detection device according to the second embodiment of the present invention.  FIG. 21  is a perspective view of an appearance of a detection device  200  shown in  FIG. 20 .  FIG. 22  is a block diagram for specifically illustrating a configuration of detection device  200  shown in  FIG. 20 . 
     With reference to  FIGS. 20-22 , illumination light source  102  (or the second light source) is a light source which emits white light  6 , for example, and it is a halogen lamp, for example. Illumination light source  102  may be implemented as a laser light source. Note, however, that using a white light source as illumination light source  102  allows detection device  200  to be implemented at a low cost. 
     Illumination light source  102  may be a light source which emits substantially monochromatic light. The monochromatic light has a wavelength corresponding to that of a peak of localized surface plasmon resonance induced in gold nanoparticle assembly  10 . The wavelength of the monochromatic light is only required to fall within a range in wavelength within twice the peak&#39;s full width at half maximum, and the line width of the monochromatic light is not particularly limited. The source of the monochromatic light may for example be a laser light source. Note that in  FIG. 21  illumination light source  102  is accommodated in the same chassis that accommodates optical trapping light source  101  therein. 
     Optical trapping light source  101  and illumination light source  102  emit laser light  5  and white light  6 , respectively, which are in turn guided via an optical fiber  110  to an optical probe  107 . Optical probe  107  includes objective lens  103  and kit  20 . White light  6  is introduced into objective lens  103  coaxially with laser light  5 . These lights are focused by objective lens  103  to irradiate sample  30  therewith. Sample  30  transmits light, which is in turn guided by optical fiber  111  to a spectroscope  105 . Note that laser light  5  and white light  6  may alternatively be radiated in mutually different directions. 
     Spectroscope  105  measures an absorption spectrum of localized surface plasmon resonance induced in gold nanoparticle assembly  10  formed in sample  30  and outputs to computation unit  106  a signal indicating a result of the measurement. Spectroscope  105  receives white light  6  radiated from illumination light source  102  to irradiate the liquid and having passed through the liquid, and accordingly, spectroscope  105  corresponds to a “photoreceiver” according to the present invention. Preferably, spectroscope  105  is a spectroscope capable of measuring a spectrum in an ultraviolet to near-infrared range (e.g., a wavelength range of 200 nm to 1100 nm). Furthermore, it is preferable that spectroscope  105  has smaller wavelength resolution. For example, the wavelength resolution of spectroscope  105  is equal to or smaller than 10 nm, equal to or smaller than 5 nm, equal to or smaller than 2 nm, or equal to or smaller than 1 nm, however, it is not limited thereto. Computation unit  106  tracks how the absorption spectrum of gold nanoparticle assembly  10  varies when gold nanoparticles  11  and  12  are aggregated by DNA hybridization. The remainder of detection device  200  in configuration is equivalent to that of detection device  100  (see  FIG. 4 ), and accordingly, will not be described repeatedly. 
       FIG. 23  is a flowchart for illustrating a method for detecting an analyte according to the second embodiment of the present invention. With reference to  FIG. 23 , the process up to step S 3  is equivalent to that in  FIG. 7 , and accordingly, will not be described repeatedly. 
     In step S 41 , illumination light source  102  starts to irradiate kit  20  for example with white light  6 . Note that step S 41  may precedes step S 3  to start radiating white light  6  before radiating laser light  5 . 
     In Step S 51 , spectroscope  105  operates to measure any absorption spectrum of localized surface plasmon resonance of any gold nanoparticle assembly  10 . If gold nanoparticle assembly  10  is present, it presents an absorption spectrum having a peak wavelength red-shifted and also having a broadened peak wavelength range. 
     In Step S 61 , computation unit  106  detects an analyte, based for example on the absorption spectrum&#39;s peak wavelength and the signal intensity presented at the peak wavelength. For example, a preliminary experiment is performed to measure a relationship between the concentration of an analyte in a sample and a signal intensity ratio in the absorption spectrum. Computation unit  106  stores this relationship previously for example as a table. Computation unit  106  calculates a signal intensity ratio from a result of a measurement done by spectroscope  105 . Computation unit  106  detects the analyte if the calculated signal intensity ratio exceeds a reference value. The reference value is previously set according to the above table. 
     Note that computation unit  106  may use the relationship defined in the above table and a signal intensity ratio obtained from a result of a measurement done by spectroscope  105  to calculate the analyte&#39;s concentration. Furthermore, a result of a preliminary experiment may be used to determine a function for deriving an analyte&#39;s concentration from a signal intensity ratio, and computation unit  106  may use the function and the intensity of a signal measured by spectroscope  105  to calculate the concentration of the analyte. 
     Furthermore, the sample&#39;s scattering spectrum or extinction spectrum may be measured, rather than its absorption spectrum. An extinction spectrum is a sum of a scattering spectrum and an absorption spectrum. Accordingly, when discussing where a peak is located, measuring a scattering spectrum or measuring an extinction spectrum is substantially equivalent to measuring an absorption spectrum. In any of the cases, localized surface plasmon presents a substantially identical spectral peak position. 
     If a DNA having a base sequence with only a single base different than the base sequence of the complementary DNA should be introduced into a sample, that DNA can hybridize with a target DNA. However, an absorption spectrum presented when the complementary DNA is introduced is different from that presented when the DNA different by only a single base is introduced. Accordingly, for example, computation unit  106  can have an absorption spectrum of a gold nanoparticle assembly formed by hybridization with the complementary DNA and an absorption spectrum of a gold nanoparticle assembly formed by hybridization with the DNA different by only a single base, previously stored therein to distinguish a mismatch of that single base. 
     Third Embodiment 
     In a third embodiment, a surface enhanced Raman scattering (SERS) spectrum is measured. Kit  20  according to the first embodiment of the present invention (see  FIG. 5 ) can be utilized as a substrate for SERS. The third embodiment employs a detection device that is equivalent in configuration to detection device  200  (see  FIGS. 20-22 ), and accordingly, will not be described repeatedly. 
     Gold nanoparticles  11  and  12  are conjugated by target DNA  18 , and, with gold nanoparticle assembly  10  formed, kit  20  is irradiated with white light. Localized surface plasmon resonance is enhanced in a gap formed between gold nanoparticles  11 ,  12 . That is, an electric field is enhanced in the gap between gold nanoparticles  11 ,  12 . In general, Raman scattering is a third-order nonlinear optical process, and accordingly, Raman scattering light has intensity enhanced non-linearly for larger electric field intensity. As the electric field is enhanced, Raman scattering light is significantly increased in intensity. Spectroscope  105  detects increased Raman scattering light. Target DNA  18  is thus detected. Note that the SERS described in this embodiment can include surface enhancement resonant Raman scattering (SERRS). 
     Fourth Embodiment 
     A detection method according to an embodiment of the present invention can be applied to a conventional detection device detecting a trace amount of an analyte, to achieve enhanced detection sensitivity and reduced detection time. Furthermore, label-free detection can be implemented. In a fourth embodiment will be described a configuration allowing apply a detection method according to an embodiment of the present invention to be applied to a DNA chip reader device. 
       FIG. 24  schematically shows a configuration of a detection device according to the fourth embodiment of the present invention.  FIG. 25  is a diagram for illustrating how a process in a detection device  400  shown in  FIG. 24  proceeds. 
     With reference to  FIG. 24  and  FIG. 25 , detection device  400  includes a DNA chip  40 , optical trapping light source  101 , objective lens  103 , illumination light source  102 , optical component  104 , an objective lens  405 , filters  406 ,  407 , a CCD camera  408  (a photoreceiver), and computation unit  106 . 
     On DNA chip  40 , generally several hundreds to several tens of thousands of spots  41  are arranged. In  FIG. 25 , only some of the spots are shown by  FIG. 25  due to a limit in drawing. Each spot  41  can be configured for example with the configuration of the  FIG. 5  kit  20  applied thereto. Each spot  41  receives a liquid dropped thereon having contained therein gold nanoparticles  11  and  12  modified with different probe DNAs, and has thus gold nanoparticles  11 ,  12  introduced therein. Each spot  41  receives a liquid dropped thereon having target DNA  18  contained therein. 
     Initially, to cause DNA hybridization, each of spots  41  is irradiated with light output from optical trapping light source  101 . This accelerates hybridization of target DNA  18  and probe DNAs  13  and  14 . In general, DNA hybridization requires about half a day. In contrast, the present embodiment allows significantly reduced hybridization reaction time. Note that, irradiating a plurality of spots  41  with light simultaneously, can reduce a period of time required to irradiate all of spots  41  with light. 
     Illumination light source  102  for example radiates white light  6  via objective lens  405  to irradiate each spot  41 . Filters  406 ,  407  are selectively set on a path of light transmitted through DNA chip  40 . 
     Filter  406  transmits light of a wavelength range including a peak wavelength of an absorption spectrum presented before DNA hybridization (e.g., the wavelength range of green (see  FIG. 19 )), while filter  406  interrupts light of any other wavelength. In contrast, filter  407  transmits light of a wavelength range including a peak wavelength of an absorption spectrum presented after DNA hybridization (e.g., the wavelength range of yellow to orange color), while filter  407  interrupts light of any other wavelength. The lights having passed through filters  406 ,  407  have light intensity depending on presence/absence of DNA hybridization in each spot  41 . 
     CCD camera  408  outputs to computation unit  106  a signal depending on the light intensity of each spot  41 . Computation unit  106  determines whether there is hybridization with target DNA  18  for each spot  41  from a ratio between a signal indicative of intensity of light transmitted through filter  406  and a signal indicative of intensity of light transmitted through filter  407 . 
     More specifically, a spot having introduced therein a probe DNA which does not hybridize with target DNA  18  has a relatively large absorption of light of the wavelength range that filter  406  transmits therethrough, whereas the spot has a relatively small absorption of light of the wavelength range that filter  407  transmits therethrough. Accordingly the spot presents relatively larger light intensity with filter  407  set. 
     In contrast, a spot having introduced therein a probe DNA which hybridizes with target DNA  18  has a relatively small absorption of light of the wavelength range that filter  406  transmits therethrough, whereas the spot has a relatively large absorption of light of the wavelength range that filter  407  transmits therethrough. Accordingly the spot presents relatively larger light intensity with filter  406  set. 
     There are two types of spots  411  and  412  depending on relative magnitude in light intensity presented with filters  406 ,  407  set. Spot  411  presents relatively large light intensity with filter  407  set. This indicates that a probe DNA that modifies a surface of a gold nanoparticle introduced into spot  411  does not hybridize with target DNA  18 . In contrast, spot  412  presents relatively large light intensity with filter  406  set. This indicates that a probe DNA that modifies a surface of a gold nanoparticle introduced into spot  412  hybridizes with target DNA  18 . 
     Note that computation unit  106  may determine whether target DNA  18  is present from only a signal indicative of light intensity presented with one of filters  406  and  407  set. Furthermore, one of filters  406 ,  407  may alone be used. 
     Furthermore, gold nanoparticles  11  having their surfaces with probe DNA  13  thereon stained with a fluorochrome, and then integrated by laser light, allow localized surface plasmon to present enhanced emission allowing highly sensitivity. 
     Furthermore, a DNA chip having a different configuration from the  FIG. 25  configuration may be used. Specifically, a DNA chip is prepared that has previously fixed in each spot  41  one of probe DNAs  13  and  14  having known base sequences. This DNA chip can be used to detect target DNA  18 . 
       FIG. 26  is a diagram for illustrating how a detection process using a DNA chip different from DNA chip  40  shown in  FIG. 25  proceeds. With reference to  FIG. 26 , DNA chip  40  has spots  40  thereon each having a different DNA  14  previously fixed thereto. Each spot  41  receives a liquid dropped thereon having contained therein gold nanoparticles  11  modified with probe DNA  13 , and also receives a liquid having target DNA  18  contained therein. The remainder of  FIG. 26  in configuration is equivalent to that of  FIG. 25 , and accordingly, will not be described repeatedly. 
     The above configuration can accelerate hybridization of target DNA  18  and probe DNAs  13  and  14  to rapidly detect an analyte or target DNA  18 . 
     Fifth Embodiment 
     As has been set forth in the second embodiment, a DNA that hybridizes with a probe DNA is not limited to a complementary DNA. If a DNA having a base sequence different from a complementary DNA is introduced into a sample, with the base sequence matching that of the complementary DNA at a rate larger than or equal to a prescribed value, that DNA can hybridize with the probe DNA. A detection device according to a fifth embodiment obtains an image of a gold nanoparticle assembly formed through light irradiation for a plurality of types of samples having introduced therein DNAs having base sequences different from that of the complementary DNA and measures each sample&#39;s absorption spectrum. The detection device then determines what type of DNA the sample has introduced therein, based on how the absorption spectrum varies with time. 
       FIG. 27  is a diagram for illustrating a probe DNA and four types of DNAs that can serve as an analyte and have mutually different base sequences. With reference to  FIG. 27 , the present embodiment employs a probe DNA identical to that used in the first embodiment (see  FIG. 3 ). More specifically, probe DNA  13  (SEQ ID NO: 1) is a single strand of DNA having a 3′ end with a thiol group (represented as SH), and a 5′ end with 12 thymines (represented as T) between the 5′ end and the thiol group. Probe DNA  14  (SEQ ID NO: 2) is a single strand of DNA having a 5′ end with a thiol group, and a 3′ end with 12 thymines between the 3′ end and the thiol group. 
     Target DNA  18  is the same as that used in the first embodiment. More specifically, target DNA  18  (SEQ ID NO: 3) is a single strand of DNA having a 5′ end and a 3′ end with 24 adenines (represented as A) therebetween. Between target DNA  18  and probe DNAs  13  and  14 , all base pairs have a complementary relationship, and accordingly, target DNA  18  is also referred to as a “complementary DNA.” 
     A target DNA  18 B (SEQ ID NO: 4) is a single strand of DNA having a 5′ end and a 3′ end with 24 thymines therebetween. Between DNA  18 B and probe DNAs  13  and  14 , all base pairs are mismatched, and accordingly, DNA  18 B is also referred to as a “completely mismatched DNA.” 
     A target DNA  18 C (SEQ ID NO: 5) is a single strand of DNA having 12 adenines adjacent to the 5′ end and 12 thymines adjacent to the 3′ end. DNA  18 C have bases with a half thereof closer to the 5′ end complementary to those of probe DNAs  13  and  14  and a half thereof closer to the 3′ end failing to match those of probe DNAs  13  and  14 , and accordingly, DNA  18 C is also referred to as a “half mismatched DNA.” 
     A DNA  18 D (SEQ ID NO: 6) is a single strand of DNA having a 5′ end and a 3′ end with thymine and adenine alternately repeated from the 5′ end toward the 3′ end. It has the same number of bases as the other DNAs, i.e. 24 bases. DNA  18 D has a complementary base and a mismatched base alternately repeated and accordingly, it is also referred to as an “alternately mismatched DNA.” 
       FIG. 28  schematically shows a configuration of a detection device according to the fifth embodiment of the present invention. With reference to  FIG. 28 , a detection device  500  is configured to be capable of obtaining an image of a vicinity of the beam waist of laser light  5  and also measure how an absorption spectrum varies with time. Detection device  500  is different from the  FIG. 4  detection device  100  that the former further includes a computation unit (or detector)  506  and a spectroscope  508 . Note that computation unit  506  may be configured to be integral with computation unit  106 . 
     More specifically, spectroscope  508  measures an absorption spectrum of localized surface plasmon resonance induced on gold nanoparticle assembly  10  formed in sample  30 , and outputs to computation unit  506  a signal indicating a result of the measurement. Spectroscope  508  can for example be a multichannel spectroscope. 
     If a DNA (e.g., a half-mismatched DNA and an alternately mismatched DNA) has a base sequence matching that of a complementary DNA at a rate equal to or larger than a prescribed value, computation unit  506  can detect that DNA as an analyte. 
     Detection device  500  provides a measurement, as below. A sample presents an absorption spectrum varying with time differently depending on what type of DNA the sample has introduced therein. The sample with the completely mismatched DNA does not present an absorption spectrum with a peak shift, whereas those with the complementary DNA, the half-mismatched DNA and the alternately mismatched DNA present a clear peak shift within several seconds to several minutes after light irradiation started. Furthermore, those with the complementary DNA, the half-mismatched DNA, and the alternately mismatched DNA have different periods of time after light irradiation started before they present peak shifts, and they present peaks shifted in amounts with different temporal change rates. Computation unit  506  tracks such a variation of a peak wavelength to determine what type of DNA a sample has introduced therein. 
     An example of a methodology of tracking how a peak wavelength varies will now be described more specifically. Computation unit  506  receives a signal indicative of an absorption spectrum from spectroscope  508  whenever a prescribed period of time (e.g., of 5 seconds) elapses. Computation unit  506  detects a peak for example from the absorption spectrum&#39;s primary and secondary differential coefficients to obtain a peak wavelength. And computation unit  506  obtains a period of time required before the peak wavelength is longer than a predetermined threshold value (e.g., 580 nm) with reference to a time at which light irradiation started. 
     Computation unit  506  previously holds a table (not shown) indicating an association between the above required period of time and types of DNA. Computation unit  506  refers to this table to determine, based on the required period of time, the type of DNA introduced into each sample. More specifically, computation unit  506  for example determines that when a sample having a DNA introduced therein requires a period of time of 0-50 seconds before the sample presents a peak wavelength longer than the predetermined threshold value the DNA is a complementary DNA. Computation unit  506  for example determines that when a sample having a DNA introduced therein requires a period of time of 50-100 seconds before the sample presents a peak wavelength longer than the predetermined threshold value the DNA is a half-mismatched DNA. Computation unit  506  for example determines that when a sample having a DNA introduced therein for example requires a period of time of 100-200 seconds before the sample presents a peak wavelength longer than the predetermined threshold value the DNA is an alternately mismatched DNA. Furthermore, if a sample having a DNA introduced therein does not present a peak shift after a period of time of 200 seconds elapsed, computation unit  506  determines that the DNA is a completely mismatched DNA. 
     Furthermore, as will be indicated hereafter, a complementary DNA presents a peak shift in a short period of time, whereas a half mismatched DNA presents a peak shift in a longer period of time. As such, instead of or in addition to calculating the above required period of time, computation unit  506  may calculate at what temporal change rate a peak wavelength is shifted in amount (i.e., a gradient of a curve shown in  FIG. 33 ). Computation unit  506  previously holds a table indicating an association between temporal change rates in amount of shift of peak wavelength and types of DNA to therefrom determine a type of DNA from a temporal change rate in amount of shift of a peak wavelength. Furthermore, the calculation of the above required period of time and the calculation of a temporal change rate in amount of shifting of peak wavelength can be used together to provide determination with increased precision. The remainder of detection device  500  in configuration is equivalent to that of detection device  100 , and accordingly, will not be described repeatedly. 
     Regarding the four types of diluted dispersion liquids having different types of DNA introduced therein as shown in  FIG. 27 , detection device  500  provides measurements, as will be described hereafter. 
       FIG. 29  presents successive photographic images of a gas-liquid interface of the diluted dispersion liquid of the complementary DNA (in a vicinity of the beam waist), as obtained after light irradiation started, and how the absorption spectrum varies with time.  FIG. 29(A)  shows images of the gas-liquid interface obtained through image pick-up device  108  for every 15 seconds with radiation of laser light  5  started at a time of 0 second. After light irradiation starts when a period of time of 150 seconds elapses light irradiation is stopped. Note that the positions respectively of liquid (L), gas (A) and gas-liquid interface (I) are not shown as they are equivalent to those shown in  FIG. 9  to  FIG. 13 . 
     For the complementary DNA, formation of a gold nanoparticle assembly is clearly measured 15 seconds after light irradiation is started. Light irradiation is further continued and as time elapses in that condition, how the gold nanoparticle assembly grows is measured. In contrast, it can be seen that once a period of time of 150 seconds has elapsed, i.e., when light irradiation is stopped, the once grown-up gold nanoparticle assembly becomes small. 
     Then, with reference to  FIG. 29(B) , this absorption spectrum is measured using spectroscope  508 . The axis of abscissa represents wavelength and the axis of ordinate represents absorbance.  FIG. 29(B)  presents curves, which represent an absorption spectrum presented 0 second, 30 seconds, 60 seconds, 90 seconds, 120 seconds, 150 seconds, and 180 second after radiation of laser light  5  is started. 
     Before light irradiation starts (or at 0 s) the absorption spectrum has a peak wavelength of 533.73 nm and presents an absorbance of 0.093 at the peak wavelength. Furthermore, after a period of time of 150 seconds elapsed, the absorption spectrum has a peak wavelength of 592.34 nm and presents an absorbance of 0.773 at the peak wavelength. Thus, the peak wavelength red-shifts as time elapses from initiation of light irradiation. Furthermore, that the absorption spectrum is broadened is also measured. 
       FIG. 30  presents successive photographic images of a gas-liquid interface of the diluted dispersion liquid of the completely mismatched DNA (in a vicinity of the beam waist) after light irradiation starts, and how the absorption spectrum varies with time.  FIG. 30  is compared with  FIG. 29 . 
     With reference to  FIG. 30(A) , for the completely mismatched DNA, even irradiated with light, no formation of a gold nanoparticle assembly is measured. 
     With reference to  FIG. 30(B) , before light irradiation starts (or at 0 s) the absorption spectrum has a peak wavelength of 531.47 nm and presents an absorbance of 0.105 at the peak wavelength. Furthermore, after a period of time of 150 seconds elapsed, the absorption spectrum has a peak wavelength of 563.36 nm and presents an absorbance of 0.326 at the peak wavelength. 
     Note that, in the example of measurement indicated in  FIG. 30 , the absorption spectrum broadens after a period of time of 150 seconds elapsed. It is believed that this is because an assembly formed without resulting from radiation of laser light  5  has flown into a photometric area, as shown in an image shown in  FIG. 30(A)  that is presented after the period of time of 150 seconds elapsed. 
       FIG. 31  presents successive photographic images of a gas-liquid interface of the diluted dispersion liquid of the half mismatched DNA (in a vicinity of the beam waist) after light irradiation starts, and how the absorption spectrum varies with time.  FIG. 31  is compared with  FIG. 29  and  FIG. 30 . 
     With reference to  FIG. 31(A) , for the half mismatched DNA, formation of a gold nanoparticle assembly through light irradiation is measured. Note, however, that as is apparent from comparing an image obtained from the half mismatched DNA and that obtained from the complementary DNA that are obtained after a period of time of 150 seconds elapsed, the half-mismatched DNA forms an assembly sparser than that formed by the complementary DNA. 
     With reference to  FIG. 31(B) , before light irradiation starts (or at 0 s) the absorption spectrum has a peak wavelength of 535.78 nm and presents an absorbance of 0.078 at the peak wavelength. Furthermore, after a period of time of 150 seconds elapsed, the absorption spectrum has a peak wavelength of 596.57 nm and presents an absorbance of 0.791 at the peak wavelength. 
       FIG. 32  presents successive photographic images of a gas-liquid interface of the diluted dispersion liquid of the alternately mismatched DNA (in a vicinity of the beam waist) after light irradiation starts, and how the absorption spectrum varies with time.  FIG. 32  is compared with  FIG. 29  to  FIG. 31 . 
     With reference to  FIG. 32(A) , for the alternately mismatched DNA, formation of a gold nanoparticle assembly through light irradiation is measured. Note however, that the alternately mismatched DNA forms an assembly smaller than that formed by the complementary DNA. 
     With reference to  FIG. 32(B) , before light irradiation starts (or at 0 s) the absorption spectrum has a peak wavelength of 537.42 nm and presents an absorbance of 0.130 at the peak wavelength. Furthermore, after a period of time of 150 seconds elapsed, the absorption spectrum has a peak wavelength of 586.08 nm and presents an absorbance of 0.738 at the peak wavelength. 
       FIG. 33  is a diagram for illustrating how the absorption spectra shown in  FIG. 29(B) ,  FIG. 30(B) ,  FIG. 31(B) , and  FIG. 32(B)  have peaks shifted. With reference to  FIG. 33 , the axis of abscissa represents time having elapsed since light irradiation started, and the axis of ordinate represents peak wavelength. As has been set forth above, light irradiation stops 150 seconds after it started. 
     The complementary DNA presents a peak wavelength red-shifted after light irradiation started before a period of time of 30 seconds elapses. A period of time required before the peak wavelength is longer than a threshold value (580 nm) is estimated to be 30 seconds. On the other hand, for a period of time after 30 seconds before 150 seconds, the peak wavelength is substantially constant. And after a period of time of 150 seconds has elapsed, i.e., when light irradiation is stopped, the peak wavelength blue-shifts. This sufficiently matches the fact that a gold nanoparticle assembly is reduced in size once light irradiation has been stopped, as has been described with reference to  FIG. 29(A) . 
     When the half mismatched DNA is compared with the complementary DNA, the former presents a peak wavelength taking more time to red-shift immediately after light irradiation is started than the latter. However, the peak wavelength also continues to red-shift for a period of time after 30 seconds before 150 seconds. A period of time that the peak shift requires is estimated to be 90 seconds. While the half mismatched DNA requires time for peak shift, it presents a peak wavelength of the same extent as that of the complementary DNA for a point in time when a period of time of 150 seconds has elapsed. 
     The alternately mismatched DNA presents a peak wavelength substantially unchanged after light irradiation started before a period of time of 60 seconds elapses. In contrast, during a period of time after 60 seconds before 90 seconds, the peak wavelength red-shifts. A period of time that the peak shift requires is estimated to be 150 seconds. When the alternately mismatched DNA is compared with the complementary DNA or the half mismatched DNA, the former takes more time to present a peak shift. 
     The completely mismatched DNA does not present a peak wavelength substantially varying while it is irradiated with laser light  5 . After a period of time of 150 seconds has elapsed the peak wavelength is temporarily red-shifted, because, as has been described with reference to  FIG. 30 , an assembly formed without resulting from light irradiation has flown into a photometric area. 
     Thus, a sample presents a peak wavelength varying differently depending on what type of DNA the sample has introduced therein. Thus, according to the present embodiment, detection device  500  tracks how a peak wavelength varies. Detection device  500  can thus determine what type of DNA a sample has introduced therein. 
     Detection device  500  according to the fifth embodiment can be used for example to identify a PCR product generated through polymerase chain reaction (PCR). Generally, when the PCR is used to determine whether a specific base sequence&#39;s DNA is amplified, a dye which emits fluorescence when it conjugates with that DNA is added to a reaction liquid, and fluorescence intensity is thus measured. In contrast, detection device  500  allows a peak wavelength&#39;s variation to be tracked to identify a PCR product without labeling with a fluorochrome. Alternatively, detection device  500  can refer to a peak shift&#39;s required period of time or a temporal change rate in amount of shifting of a spectrum to be used to assist in specifying an unknown DNA base sequence. 
     Note that the detection device of the fifth embodiment is also applicable to the DNA chip reader device described in the fourth embodiment. More specifically, a DNA chip has a plurality of spots each holding gold nanoparticles modified with a different probe DNA. A plurality of spots each receive a liquid dropped thereon having a target DNA contained therein and are subsequently simultaneously irradiated with light to measure how their absorption spectra vary with time. What types of DNA are present can thus be determined for the plurality of spots collectively, and an analyte(s) (or a target DNA(s)) can be detected in a reduced period of time. 
     Note that in the fifth embodiment, a complementary DNA corresponds to a “first target DNA,” and either one of a half mismatched DNA and an alternately mismatched DNA corresponds to a “second target DNA.” When the target DNA is either one of the “first target DNA” and the “second target DNA,” computation unit  506  can determine whether the target DNA is the “first target DNA” or the “second target DNA,” based on how a spectrum measured by spectroscope  508  varies with time. 
     While in the above has been described a configuration with detection device  500  including both image pick-up device  108  and spectroscope  508 , image pick-up device  108  is not an essential component for detection device  500 . Accordingly, image pick-up device  108  may be dispensed with. 
     Sixth Embodiment 
     In a sixth embodiment, the substrate holding a droplet is not used and a micro channel chip is instead used. A detection device that is used in the present embodiment is equivalent in configuration to the  FIG. 4  detection device  100  except for the micro channel chip and accordingly, the detection device will not be described repeatedly. 
       FIG. 34  is a schematic diagram for illustrating a micro channel chip in a state before injection is started.  FIG. 35  is a schematic diagram for illustrating a micro channel chip in a state after injection is started. 
     With reference to  FIG. 34 , a micro channel chip  600  has an inlet  610 , a micro channel  620 , and an outlet  630 . Before injection is started, inlet  610  has introduced therein a sample containing target DNA  18  and gold nanoparticles  11  and  12 . 
     Micro channel chip  600  is provided with valves  641 - 643  for controlling in amount (or flow rate) the sample passing through micro channel  620 . Valves  641 - 643  are each implemented for example as a piezoelectric device. Valve  641  is provided at an end of micro channel  620  adjacent to inlet  610 . Valve  642  is provided in the course of micro channel  620 . Valve  643  is provided at an end of micro channel  620  adjacent to outlet  630 . However, the number of valves and their locations are not particularly limited. 
     Subsequently, with reference to  FIG. 35 , when the sample is passed, laser light  5  is introduced into micro channel  620 . Thus, gold nanoparticle assembly  10  is formed at a laser spot (indicated by laser light  5 ). Gold nanoparticle assembly  10  formed passes through the remainder of micro channel  620  and is stored in outlet  630 . 
     In the first embodiment, laser light  5  is positioned to irradiate a gas-liquid interface therewith. This is done because at the gas-liquid interface a dispersion medium evaporates, which locally increases gold nanoparticles  11  and  12  and target DNA  18  in concentration. This increases the number of gold nanoparticles  11  and  12  and target DNA  18  passing across the laser spot and thus allows a gold nanoparticle assembly to be formed in a further shorter period of time. 
     The present embodiment that employs the micro channel chip allows gold nanoparticles  11  and  12  and target DNA  18  to be present in a narrow, limited region in micro channel chip  620  and also allows that region to be irradiated with laser light. This provides an increased probability of gold nanoparticles  11  and  12  and target DNA  18  passing across a laser spot (that is, a ratio of the number of gold nanoparticles  11  and  12  and target DNA  18  in a sample that pass across the laser spot to the total number of gold nanoparticles  11  and  12  and target DNA  18  in the sample, is increased). As a result the gold nanoparticle assembly can be formed in a reduced period of time. With gold nanoparticles  11  and  12  and target DNA  18  present in a narrow, limited region, it is not essential to position laser light  5  at the gas-liquid interface. 
     Hereinafter, an example of a result of a measurement using the micro channel chip will be described.  FIG. 36  is a cross section of micro channel chip  600  taken along a line XXXVI-XXXVI shown in  FIG. 35 . With reference to  FIG. 35 , micro channel  620  has a width (i.e., a distance between side surfaces of micro channel  20 ) of 350 μm. Micro channel  620  has a height (a distance between a ceiling  620   a  of micro channel  620  and a bottom surface  620   b  of micro channel  620 ) of 100 μm. A distance between a lower surface of micro channel chip  600  in the z direction and bottom surface  620   b  of micro channel  620  is 650 μm. 
     A liquid mixture (volume: 1.0 μL) of a dispersion liquid of gold nanoparticles  11 , a dispersion liquid of gold nanoparticles  12 , and a dispersion liquid of a target DNA (or complementary DNA)  18  with the target DNA having a concentration of 33 pM, was passed through micro channel  620 . At the time, as shown in  FIG. 37 , a gas-liquid interface is formed in the course of micro channel  620 . Laser light  5  was radiated in the z direction from below upward to irradiate micro channel  620 . Objective lens  103  having a magnification of 40 times was used to adjust an optical system to form a beam waist in a vicinity of a gas-liquid interface of a meniscus internal to the liquid in a direction (i.e., in the x direction) along a channel formed on bottom surface  620   b  of micro channel  620 . Laser light  5  had a wavelength of 1064 nm and at the beam waist had an output of 0.4 W. 
       FIG. 37  is an optical transmission image of a vicinity of a gas-liquid interface formed in the micro channel, as obtained via an objective lens of a magnification of 10 times before light irradiation starts.  FIG. 38  presents successive photographic images (or optical transmission images) of a vicinity of the beam waist in micro channel  620  after light irradiation started. 
       FIGS. 37 and 38  show a state in a vicinity of the beam waist in a vicinity of a gas-liquid interface formed in micro channel  620  having introduced therein a liquid mixture (volume: 1 μL) of a dispersion liquid of gold nanoparticles  11  modified with probe DNA  13  (concentration: 5.0 nM), a dispersion liquid of gold nanoparticles  12  modified with probe DNA  14  (concentration: 5.0 nM), and a diluted dispersion liquid of a complementary DNA (concentration: 100 pM) of equal amounts. The dispersion liquid of gold nanoparticle  11 , the dispersion liquid of gold nanoparticle  12 , and the diluted dispersion liquid of the complementary DNA are equivalent in concentration to those described with reference to  FIG. 29 . Objective lens  103  has a magnification of 40 times. 
     With reference to  FIG. 38 , an assembly of gold nanoparticles is formed in a vicinity of the beam waist within 30 seconds, similarly as shown in the successive photographs shown in  FIG. 29(A) . In  FIG. 38 , however, a gas-liquid interface different in geometry from that of  FIG. 29(A)  is presented, and accordingly, how the gold nanoparticle assembly is formed is slightly different. Note that although not shown in the figure, when an absorption spectrum presented in a vicinity of the beam waist is measured, an absorbance increasing as time elapses and a peak shifting as time elapses are confirmed, similarly as has been confirmed in the absorption spectrum shown in  FIG. 29(B)   
     If micro channel  620  has a width larger than the laser spot&#39;s size (or diameter), a portion of gold nanoparticles  11  and  12  and target DNA  18  dispersed in the liquid may pass through micro channel  620  without passing across the laser spot. Accordingly, preferably, micro channel  620  and the laser spot have a width and a diameter, respectively, determined to have a relationship in magnitude so that micro channel  620  has the width equal to or smaller than the diameter of the laser spot. Note, however, that, as shown in  FIG. 36  to  FIG. 38 , if micro channel  620  has a width (350 μm) larger than the laser spot&#39;s diameter (several tens μm), formation of a gold nanoparticle assembly is confirmed. Thus, micro channel  620  having a width larger than the laser spot&#39;s diameter is not a requirement. 
     Seventh Embodiment 
     In a seventh embodiment will be described an effect of a sample bearing surface&#39;s affinity for a sample&#39;s liquid (or dispersion medium). Specifically, a super-hydrophilic substrate is used. A detection device that is used in the present embodiment is equivalent in configuration to the  FIG. 4  detection device  100  and accordingly, the detection device will not be described repeatedly. Hereafter initially a comparative example using a hydrophobic substrate will be described. 
       FIG. 39  is an enlarged view of a configuration in a vicinity of a kit using a hydrophobic substrate. With reference to  FIG. 39 , substrate  21  is a sheet glass (e.g., a cover glass) equivalent to that used in the first embodiment, and has a hydrophobic upper surface  21   a.    
     Sample  30  dropped on substrate  21  had a concentration of 10 nM and a volume of 5 μL. In other words, sample  30  contained a complementary DNA in an amount of substance of 10 nM×5 μL=50 fmol (1 fmol=10 −15  mol). The droplet had a diameter of 5 mm. In this case, an optical system was adjusted to position a beam waist at a perimeter of the droplet that is 15 μm away from the surface of the substrate. The beam waist had a laser output of 0.2 W. 
       FIG. 40  is an image of a diluted dispersion liquid of a complementary DNA on the hydrophobic substrate in a vicinity of the beam waist after light irradiation. With reference to  FIG. 40 , when hydrophobic substrate  21  is used, a gold nanoparticle assembly is formed when the beam waist is positioned adjacent to an edge of the droplet with respect to the horizontal direction (or the xy plane), i.e., when the beam waist is positioned in a vicinity of gas-liquid interface (I). On the other hand, although not shown in the figure, when laser light  5  is radiated with the beam waist positioned in a vicinity of the center of the droplet, there is not formed any substantial gold nanoparticle assembly. 
       FIG. 41  is an enlarged view of a configuration in a vicinity of a kit using a super-hydrophilic substrate. With reference to  FIG. 41 , substrate  22  is a cover glass having an upper surface  22   a  processed to be super-hydrophilic. Note that while substrate  22  has upper surface  22   a  processed to be entirely super-hydrophilic, it may have upper surface  22   a  partially so processed. In other words, substrate  22  is only required to have upper surface  22   a  with at least a sample liquid holding region  22   b  having super-hydrophilicity. 
     Substrate  22  can be made super-hydrophilic in any of various known methods. In the present embodiment, upper surface  22   a  sufficiently cleaned with acetone was sprayed with a super-hydrophilic coating agent (a cell face coat produced by MARUSYO SANGYO CO., LTD.). Furthermore, substrate  22  thus sprayed was dried at 60 degrees centigrade for 30 minutes. Note that substrate  22  can also be made super-hydrophilic by sufficiently cleaning upper surface  22   a  with ethanol, spraying the cleaned surface with a super-hydrophilic coating agent, and air-drying the sprayed substrate for one day or more. 
     Sample  30  dropped on substrate  22  had a concentration of 100 pM and a volume V of 5 μL. In other words, sample  30  contained a complementary DNA in an amount of substance of 100 pM×5 μL=500 amol (1 amol=10 −18  mol). Upper surface  22   a  processed to be super hydrophilic allows the droplet to spread thereon and the droplet had a radius R of 5 mm. 
     As has been described in the first embodiment, when sample  30  has volume V, radius R and maximum height H, a relational expression of V=2πR 2 H/3 is established. When the relational expression has V and R substituted by 5 μL and 5 mm, respectively, H=0.287 mm is obtained. Accordingly, the droplet&#39;s tangent Lt and the substrate  22  upper surface  22   a  form a contact angle θ=3.3 degrees based on a relational expression of tan θ=(0.287/5)=0.0573. Note that for a hydrophobic substrate shown in  FIG. 39 , contact angle θ is calculated to be 24.7 degrees. 
     In this case, an optical system was adjusted to position a beam waist in a vicinity of the center of the droplet in a range within 15 μm as measured from upper surface  22   a . The laser light at the beam waist had an output of 0.2 W, similarly as provided when the hydrophobic substrate is used. 
       FIG. 42  is an image of a diluted dispersion liquid of a complementary DNA on the super hydrophilic substrate in a vicinity of the beam waist after light irradiation. With reference to  FIG. 42 , when super hydrophilic substrate  22  is used, then, even with the beam waist located in a vicinity of the center of the droplet, it is confirmed that a gold nanoparticle assembly is formed about 40 seconds after light irradiation is started. 
     Thus when a super hydrophilic substrate is compared with a hydrophobic substrate, the former allows a gold nanoparticle assembly to be formed in a wide area in the horizontal direction (or in a direction along the substrate&#39;s surface) including a vicinity of the center of the substrate. The present embodiment can thus eliminate the necessity of adjusting the beam waist to be positioned precisely at a position adjacent to a perimeter of a droplet. This allows increased tolerance in positionally adjusting the focal point of objective lens  103  (see  FIG. 4 ) in the direction along the substrate&#39;s surface. 
     It should be understood that the embodiments disclosed herein have been described for the purpose of illustration only and in a non-restrictive manner in any respect. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the meaning and scope equivalent to the terms of the claims. 
     REFERENCE SIGNS LIST 
       10 : gold nanoparticle assembly;  11 ,  12 : gold nanoparticle;  13 ,  14 : probe DNA;  18 : target DNA;  18 B- 18 D: DNA;  5 : laser light;  6 : white light;  20 : kit;  21 : substrate;  24 : liquid level guide;  30 : sample;  31 : gas-liquid interface;  100 ,  200 ,  400 ,  500 : detection device;  101 : optical trapping light source;  102 : illumination light source;  103 ,  405 : objective lens;  104 : optical component;  105 ,  508 : spectroscope;  106 ,  506 : computation unit;  107 : optical probe;  108 : image pick-up device;  109 : laser displacement meter;  110 ,  111 : optical fiber;  112 : adjustment mechanism;  114 : xyz-axis stage;  115 : immersion oil;  40 : DNA chip;  41 ,  411 ,  412 : spot;  406 ,  407 : filter;  408 : CCD camera;  600 : micro channel chip;  610 : inlet;  620 : micro channel;  630 : outlet;  641 - 643 : valve.