JP4969923B2 - Sample measurement method - Google Patents

Description

  The present invention relates to a sample measurement method and a sample measurement apparatus, and more particularly, to collect a sample liquid sample including a sample dispensed on a substrate to be measured, and to measure a sample for measuring optical information of the sample. The present invention relates to a measurement method and a sample measurement device.

  Research on biopolymers has been conducted on various subjects such as clinical testing, drug discovery, and development in the field of environmental and food testing, but detection for analyzing information possessed by this biopolymer with high sensitivity. Devices are becoming increasingly important.

  In a conventional detection apparatus, a sample liquid containing a specimen is placed on a substrate to be measured, and light is applied to the specimen, thereby receiving fluorescence emitted from a fluorescent dye of the specimen. For example, a laser beam is applied to a reaction region of a specimen on a sample stage, and fluorescence from the reaction region is detected by a photodetector.

A substrate to be measured of this type is formed with a plurality of recesses called wells arranged in each of which a sample liquid containing a specimen is dispensed using a pipette of a dispenser. (For example, refer to Patent Document 1).
International Publication No. 2006/013832

  For the substrate in which the specimen is dispensed in each recess, a plastic plate is welded as necessary to prevent foreign matters from entering the sample liquid containing the specimen in the recess from the outside.

  However, a small amount of air may be mixed in the sample liquid containing the specimen. When air is mixed, an air layer (bubbles) is formed in the sample liquid containing the specimen in the concave portion of the substrate.

  For example, as shown in FIGS. 21 and 22, the sample liquid 3S including the specimen 3 is collected in the upper corner portion 1001 which can be a contact portion between the substrate 2 and the plastic plate 6, and the central portion where the measurement light 1000 is irradiated is collected. The sample liquid 3S containing the specimen 3 is reduced. That is, the sample liquid 3S containing the specimen 3 may be unevenly distributed in the upper corner portion 1001 and separated from the bubbles 250. In this case, there is a problem that the detection sensitivity of the specimen 3 is lowered because the amount of measurement light obtained from the specimen 3 is reduced.

  Therefore, in order to solve the above problem, the present invention can collect the sample liquid containing the specimen at an arbitrary position in order to prevent the specimen from being unevenly distributed by the air layer (bubble) formed in the sample liquid containing the specimen. An object of the present invention is to provide a sample measurement method and a sample measurement apparatus that can prevent a decrease in detection sensitivity when detecting optical information from a specimen.

In order to achieve the above object, the sample measuring method of the present invention is a transparent cover that is transparent and stretchable after a sample liquid containing a specimen to be measured is contained in the recess of the substrate on which the recess is formed. Sealing the sample solution in the recess by a member;
The cover member has a hydrophilic treatment at least in a portion corresponding to the recess,
The light exit / incident part of the measurement part is applied from the outer surface side of the cover member, and the surface of the cover member on the concave side is pushed in until it comes into contact with the sample. The specimen is brought into contact with the light exit / incident part via the cover member in a state where the specimens are gathered on the bottom surface side, and optical information of the specimen is measured.

In the sample measurement method of the present invention, the recess is subjected to a hydrophobic treatment, and vibration is applied to the recess where the sample solution is sealed, so that the sample solution containing the specimen is placed on the recess side of the cover member. The optical information possessed by the specimen is measured in a state where the specimens are gathered on the bottom surface side or the bottom surface side of the recess .

The sample measurement method of the present invention is characterized in that a plurality of the recesses are formed on the substrate .

The sample measurement method of the present invention is characterized in that the bottom of the concave portion is transparent and is subjected to hydrophilic treatment, and optical information of the specimen is measured from the transparent portion .

The sample measurement method of the present invention is characterized in that fluorescence information is measured from the specimen by irradiating the specimen with excitation light .

  According to the sample measuring method of the present invention, the sample liquid containing the specimen can be concentrated at an arbitrary position in the container to prevent the specimen from being unevenly distributed in the container, and the optical information of the specimen that is the sample is measured. At this time, since the sample can be concentrated so that the sample liquid containing the sample does not scatter in the container, it is possible to prevent the measurement sensitivity of the optical information of the sample from being lowered and to perform high-sensitivity measurement.

  According to the sample measuring apparatus of the present invention, the sample liquid containing the specimen can be concentrated at an arbitrary position in the container to prevent the specimen from being unevenly distributed in the container, and the optical information of the specimen that is the sample is measured. At this time, since the sample can be concentrated so that the sample liquid containing the sample does not scatter in the container, it is possible to prevent the measurement sensitivity of the optical information of the sample from being lowered and to perform high-sensitivity measurement.

  FIG. 1 is a diagram showing a preferred embodiment of the sample measuring apparatus of the present invention.

  A sample measurement apparatus 10 shown in FIG. 1 is an apparatus for carrying out a preferred embodiment of the sample measurement method of the present invention.

  In the sample measuring apparatus 10, the sample liquid 3 </ b> S including the specimen 3 is dispensed to the measurement target substrate 2 at a plurality of dispensing positions. The sample measuring device 10 collects the specimen 3 by collecting the sample liquid 3S including the specimen 3 on the cover 6, for example, by applying a centrifugal force to the sample liquid 3S including the dispensed specimen 3. 3 measures the light information (fluorescence information).

  The sample measuring apparatus 10 shown in FIG. 1 includes a rotating device 60 and a control unit 100. The rotating device 60 includes a motor 61 and a rotating plate 62. The output shaft 63 of the motor 61 is connected to the rotation center 64 of the rotation plate 62, and the motor 61 sets the rotation plate 62 along the rotation direction R around the rotation center 64 according to a command from the control unit 100. It can be continuously rotated at the specified rotation speed. One or more substrates 2 are detachably mounted on the rotating plate 62.

  In the embodiment of the present invention, the specimen 3 is a sample to be measured, and the sample liquid 3S is a liquid containing the specimen 3.

  FIG. 14 to FIG. 16 show a comparative example in which the sample liquid 3S including the specimen 3 is unevenly distributed in the concave portion 4, and is not in a state of being concentrated at an arbitrary position in the concave portion 4. .

  In FIG. 14 and FIG. 16, since the sample liquid 3S containing the specimen 3 is extremely unevenly distributed at the bottom corner 1002 of the recess 4, the specimen 3 is located at the center of the sample liquid 3S containing the specimen 3 that is exposed to the measurement light. Less.

  FIG. 15 shows a comparative example in which the sample liquid 3S including the specimen 3 is extremely unevenly distributed in the recess 4, and in a state where the sample liquid 3S is concentrated at an arbitrary position in the recess 4. Absent. In FIG. 15, since the sample liquid 3S including the specimen 3 is extremely unevenly distributed in the upper corner portion 1001 of the recess 4, the specimen 3 is reduced in the central portion of the sample liquid 3S including the specimen 3 to which the measurement light is applied. The upper corner portion 1001 is a contact portion between the concave portion 4 of the substrate 2 and the inner surface of the cover member 6 such as a plastic plate.

  In the embodiment of the present invention, “collecting the sample liquid 3S including the specimen 3 in the center” does not mean that the sample liquid 3S including the specimen 3 illustrated in FIGS. The sample liquid 3S including the specimen 3 is accumulated in a disc shape without being unevenly distributed at an arbitrary position on the inner surface 6B side of the cover member 6 or the bottom surface 4C side of the concave portion 4.

  Here, with reference to FIG. 2 and FIG. 3, the DNA chip 1 which is a measurement object will be described.

  The DNA chip 1 is also called a DNA microarray, and a sample solution including a specimen 3 as a plurality of samples is arranged at each dispensing position on a substrate 2 such as a slide glass. As shown in FIG. 3, the concave portions 4 at the respective dispensing positions on the substrate 2 are arranged in high density and arrayed. In this example, the specimen 3 is a DNA fragment, and each specimen 3 is labeled with a fluorescent dye. The DNA chip 1 includes an affiliometric type manufactured using semiconductor technology and a Stanford type having a pin spot. The specimen 3 is a reagent or a biological sample, for example, and is dispersed in a sample liquid.

  FIG. 3 shows an example of a cross-sectional structure of the substrate 2, and the recesses 4 called a plurality of wells are formed in high density. These recesses 4 are formed in a trapezoidal shape when viewed in cross section, and are tapered from the opening 4B to the bottom 4C of the recess 4. In the example of FIG. 3, a raised portion 5 is formed along the vicinity of the edge of each recess 4. A sample liquid 3S including the specimen 3 is accommodated in the recess 4. For example, the sample solution 3S containing the specimen 3 of 0.5 μL or less is accommodated in the recess 4. Each specimen 3 is used for extracting a large amount of information related to the specimen 3 by performing parallel processing when a reaction occurs or the characteristics of the specimen 3 are detected.

  FIG. 4 shows a state in which the sample liquid 3S containing the specimen 3 is discharged from the guide passage 30 of the tapered portion 25 of the nozzle 20 and the specimen 3 is dispensed into the recess 4. The guide passage 30 is gently formed so that the inner diameter gradually decreases toward the distal end portion 24.

  FIG. 5 shows a state before the transparent resin cover member 6 is placed on the raised portion 5 of the substrate 2 after the specimen 3 is dispensed into the respective recesses 4. FIG. 6 shows a state in which the substrate 2 and the cover member 6 are welded, for example, by ultrasonic vibration, and the cover member 6 seals the inside of the recess 4.

  The substrate 2 manufactured as shown in FIG. 6 is mounted on a rotating plate 62 as a mounting portion of the substrate 2 shown in FIG. Each board | substrate 2 is mounted in the rotating plate 62 in the state demonstrated below. In other words, each substrate 2 can be rotated around a rotation center 64 located on the extension in the depth direction of the recess 4 of the substrate 2 shown in FIG. Each substrate 2 is arranged along a direction T orthogonal to a radius 77 from the rotation center 64 of the rotating plate 62.

  As a result, as shown in FIG. 1, the substrate 2 rotates together with the rotating plate 2, whereby a centrifugal force acts on the sample liquid 3 </ b> S containing the specimen 3 having a density higher than that of air in the recess 4, thereby The contained sample liquid 3S can be concentrated on the outermost surface (the inner surface 6B of the cover member 6).

  In the example of FIG. 1, the rotation center 64 positioned on the extension in the depth direction of the recess 4 is not the opening 4B side of the recess 4 but the rotation center positioned on the bottom 4C side of the recess 4. Thereby, since the specimen 3 is pushed away from the rotation center 64 by centrifugal force, only the sample liquid 3S containing the specimen 3 having a density higher than that of air can be concentrated at the center on the inner surface 6B side of the cover member 6. it can. That is, in the comparative example shown in FIG. 15, unlike the state in which the sample liquid 3S containing the specimen 3 specimen 3 is unevenly distributed in the upper corner portion 1001, in the example shown in FIG. The sample liquid 3S including 3 is not unevenly distributed in the upper corner, and can be collected with an average thickness along the diameter direction of the opening 4B of the recess 4. That is, in the example of FIG. 1, the sample liquid 3S containing the specimen 3 can be uniformly gathered not only in the upper corner but also in the center on the inner surface 6B of the cover member 6. It is possible to prevent the phenomenon of decreasing.

  Next, a preferred example of the sample measuring method of the present invention will be described with reference to FIG. FIG. 7 is a flowchart showing an example of a method for producing a dispensed specimen including a sample measuring method.

  In step ST1 of FIG. 7, when the suction / discharge driving unit 12 of FIG. 4 is operated, a predetermined amount of sample is stored in the guide passage 30 of the tapered portion 25 of each nozzle 20 shown in FIG. The sample liquid 3S containing 3 is aspirated.

  Next, in step ST <b> 2 of FIG. 7, each nozzle 20 is positioned with respect to each recess 4 of the substrate 2 as shown in FIG. 4. The control unit 100 operates the suction / discharge driving unit 12. As shown in FIG. 4, the sample liquid 3 </ b> S containing a predetermined amount of the specimen 3 is contained in the recess 4 from the tip 24 with the tip 24 of each nozzle 20 inserted into the opening 4 </ b> B of the recess 4. Vomited.

  Next, in step ST3 of FIG. 7, as shown in FIGS. 5 and 6, the cover member 6 is placed on the substrate 2 side, and the cover member 6 and the substrate 2 are welded. At this time, care must be taken so that the specimen is not unevenly distributed in the recess 3 due to an impact during handling. By sealing with the cover member 6, the sample liquid 3S including the specimen 3 in the recess 4 can be prevented from leaking to the outside.

  In this way, the substrate 2 in which the sample liquid 3S including the specimen 3 is sealed in the recess 4 is heated in step ST4 of FIG. 7 to promote, for example, the reaction between the reagent and the specimen.

  7, the sample liquid 3S including the specimen 3 is collected by applying a centrifugal force, and only the sample liquid 3S including the specimen 3 is collected on the inner surface 6B side of the cover member 6 separately from the bubbles 250.

  When collecting the specimen 3, it is performed as follows. For example, each substrate 2 is set on the rotating plate 62 shown in FIG. In this case, each substrate 2 is positioned with respect to the rotating plate 62 so that the rotation center 64 is positioned at a position extended from the bottom 4C side of the recess 4 of the substrate 2. That is, each substrate 2 is arranged along a direction T perpendicular to the radius 77 of the turntable 62.

  When the motor 61 in FIG. 1 is driven by a command from the control unit 100, the rotating plate 62 continuously rotates around the rotation center 64. Thereby, the sample liquid 3S containing the specimen 3 having a density higher than that of air (bubbles 250) can be collected, and only the sample liquid 3S containing the specimen 3 can be gathered on the inner surface side of the cover member 6 separately from the bubbles 250. . In this case, as a condition for rotating the substrate 3, the rotational speed is increased until the centrifugal force generated by the rotation compensates for the concentration of the sample liquid 3 </ b> S including the specimen 3 in the recess 4. For example, a centrifugal force of 6 g can be applied to the sample solution 3S containing 0.5 μL of the specimen 3 at a rotational speed of 13000 rpm. At this time, if the hydrophilic treatment is performed on the inner wall of the recess 4 and the inner wall of the cover member, the specimen 3 can be easily moved.

  As a result, the occurrence of uneven distribution in the liquid specimen 3 can be prevented, the sample liquid 3S containing the specimen 3 can be concentrated, and a decrease in measurement sensitivity when detecting fluorescence intensity from the specimen 3 to be performed later is prevented. it can.

  In step ST6 of FIG. 7, the fluorescence intensity of each specimen 3 is measured using the fluorescence intensity measuring apparatus 400 illustrated in FIG.

  The fluorescence intensity measuring apparatus 400 in FIG. 8 can also be referred to as a specimen optical information recognition apparatus, and includes a light measuring unit 420 and an optical waveguide 422. The optical waveguide 422 includes an optical fiber 423 and a lens 428. The optical fiber 423 propagates light between the light measurement unit 420 and the specimen 3.

  The light measurement unit 420 includes a light source 416, a light detection unit 418, and a beam splitter 426, and light generated by the light source 416 passes through the beam splitter 426 and is collected by a lens 428, and an optical fiber 423. The sample 3 is irradiated through. The fluorescence information generated from the specimen 3 by the light irradiation is received by the light detection unit 418 by the beam splitter 426 through the optical fiber 423 and the lens 428, so that an analyzer (not shown) analyzes the fluorescence intensity of the specimen 3. .

  Next, another preferred embodiment of the sample measuring apparatus and sample measuring method of the present invention will be described with reference to FIG.

  In the embodiment of FIG. 9, the difference from the embodiment shown in FIGS. 1 to 8 is the orientation of the substrate 2 on the rotating plate 62, and the embodiment of FIG. Since it is the same as that of embodiment shown in FIG. 8, description of embodiment shown in FIGS. 1-8 is used.

  In the embodiment of FIG. 1, each substrate 2 is positioned with respect to the rotating plate 62 so that the rotation center 64 is positioned at a position extended from the bottom 4 </ b> C side of the recess 4 of the substrate 2. When the motor 61 is driven by a command from the control unit 100, the rotating plate 62 continuously rotates at a rotation speed set in advance around the rotation center 64. Thereby, the sample liquid 3S containing the specimen 3 is not unevenly distributed, but the sample liquid 3S containing the specimen 3 is collected again by centrifugal force due to rotation, and only the sample liquid 3S containing the specimen 3 is separated from the bubbles 250. The cover member 6 can be concentrated on the inner surface side.

  On the other hand, in the embodiment of FIG. 9, the rotation center 64 located on the extension in the depth direction of the recess 4 is the rotation center located on the cover member 6 side of the recess 4. That is, each substrate 2 is arranged along a direction T perpendicular to the radius 77 of the turntable 62, and the cover member 6 is located at a position facing the rotation center 64.

  In this case, the condition for rotating the substrate 3 is such that the rotation speed is increased until the centrifugal force generated by the rotation supplements the concentration of the sample liquid 3S including the specimen 3 in the recess 4. If the inner wall of the recess 4 is subjected to a hydrophilic treatment, the sample liquid 3S including the specimen 3 in the recess 4 can be easily moved. The sample liquid 3S including the specimen 3 is concentrated on the bottom 4C side of the concave portion 4 opposite to the inner surface of the cover member 6 by the centrifugal force caused by the rotation.

  Even in this case, since the sample liquid 3S containing the specimen 3 can be collected, when the fluorescence intensity is detected by irradiating the specimen 3 with light, the measurement sensitivity of the optical information of the specimen which is a sealed sample is lowered. This makes it possible to measure with high sensitivity.

  Next, still another preferred embodiment of the present invention will be described with reference to FIGS.

  In the embodiment shown in FIGS. 10 to 12, the sample liquid 3 </ b> S including the specimen 3 to be measured is dispensed at a plurality of dispensing positions on the substrate 2, and the sample liquid 3 </ b> S including the specimen 3 is gathered to collect the specimen 3. It is the measurement method of the sample which obtains the optical information. FIG. 10 shows a measurement apparatus 400 having the same fluorescence intensity as shown in FIG.

  In the recess 4 formed at the dispensing position shown in FIG. 11, the sample liquid 3S containing the specimen 3 has already been stored in the same manner as in the above-described embodiment, and the recess 4 of the substrate 2 is a transparent cover member. 6 is sealed.

  As the cover member 6, for example, a film having a thickness of 0.1 to 0.3 mm is used. The cover member 6 is desirably used in an optically transparent state (in particular, a wavelength of 500 to 800 nm), and a refractive index matching agent is applied to the outer surface of the film as necessary. As the cover member 6 in this case, a transparent stretchable film is used, and the same material as the base material, for example, a polycarbonate film, a polypropylene film, a polyethylene film, a laminated laminate film, or the like can be used. The substrate 2 is disposed on the mounting portion 162.

  In this embodiment, since steps ST1 to ST4 in the flowchart shown in FIG. 7 are the same, the description is used.

  In the flowchart shown in FIG. 7, after performing steps ST <b> 1 to ST <b> 4, as shown in FIG. 11, the optical fiber 423 that is the light incident / incident part of the fluorescence intensity measuring device is positioned on each recess 4. The Then, as shown in FIG. 12, the tip of the optical fiber 423 is pressed against the film-like cover member 6, and pushed in along the G direction until the inner surface of the cover member 6 comes into contact with the sample liquid 3 </ b> S containing the specimen 3. It is.

  As a result, the sample liquid 3S containing the specimen 3 is pressed against the distal end portion of the optical fiber 423 and the periphery thereof via the cover member 6 having elasticity, and as a result, the specimen 3 becomes a film-like cover member 6. Thus, the optical fiber 423 is concentrated at the end of the optical fiber 423. By doing so, it is not always necessary to use the step of collecting the sample liquid 3S including the specimen 3 using the centrifugal force generated by the rotation as described above. If the cover member 6 has stretchability, the substrate 2 may be transparent or not transparent. Further, the bottom of the recess 4 of the substrate 2 may be transparent or not transparent.

  Further, instead of the cover member 6 not having elasticity, the bottom of the concave portion 4 of the substrate 2 may have elasticity, and in this case, the tip of the optical fiber 423 extends from the bottom side of the concave portion 4. It is pushed and pressed against the sample solution 3S containing the specimen 3.

  In the present embodiment, the sample liquid 3S including the specimen 3 is accommodated in the recess 4 formed at each dispensing position. The substrate 2 in which the concave portion 4 is sealed with the transparent cover member 6 is arranged, the tip end portion of the optical fiber 423 is applied from the outer surface side of the cover member 6 having elasticity, and the inner surface 6B side of the cover member 6 faces the specimen 3. It pushes in until it contacts, and the sample 3 is pressed against the end surface of the optical fiber, and as a result, the sample 3 is brought into a state of being concentrated on the end of the optical fiber 423 through the film. In this state, the measurement light can be irradiated from the optical fiber 423 to the specimen 3 and the detection light (excitation light) of the specimen 3 can be taken in the measurement while the tip of the optical fiber 423 is pushed in. Since the specimen 3 comes into contact with the specimen 3 without passing through the air layer, it is more effective to prevent the measurement sensitivity from being lowered when the fluorescence intensity is detected by irradiating the specimen 3 with light.

  FIG. 13 shows another embodiment of the present invention.

  In the embodiment described above, the inner wall of the recess 4 of the substrate 2 is preferably subjected to a hydrophilic treatment. However, in the example of FIG. 13, a hydrophobic treatment portion 295 is formed on the inner wall of the recess 4 of the substrate 2. The mounting portion 162 on which the substrate 2 is placed is subjected to vibration by the ultrasonic vibration portion 270. As a result, the sample liquid 3S containing the specimen 3 dispensed in the recess 4 of the substrate 2 can be concentrated at the center of the bottom surface of the recess 4. Since the sample liquid 3S including the specimen 3 can be concentrated at the center of the bottom surface of the recess 4, it is possible to prevent the measurement sensitivity from being lowered when the specimen 3 is irradiated with light to detect the fluorescence intensity. In this case, the specimen 3 in the recess 4 is not necessarily sealed, and the specimen may be a sealed sample or an unsealed sample.

  In the embodiment of the present invention, the sample liquid 3S containing the specimen 3 to be measured is accommodated in the concave portion 4 of the substrate 2, the bottom of the concave portion 4 is transparent, and the sample containing the specimen 3 in the concave portion 4 is contained. The liquid 3S is sealed with a transparent cover member 6. Since the sample liquid 3S including the specimen 3 is collected in the recess 4 and the optical information of the specimen 3 is measured, when the optical information of the specimen 3 that is the sample is measured, the specimen that is the sample in the recess 4 3 can be gathered so as not to be scattered, so that the measurement sensitivity of the optical information of the specimen 3 is prevented from being lowered, and high-sensitivity measurement is possible.

  Further, in the embodiment of the present invention shown in FIG. 1, the specimen 3 sufficient for measurement is averaged not only on the periphery of the inner surface 6B of the cover member 6 but also on the center of the inner surface 6B. When detecting the fluorescence intensity, it is possible to prevent the measurement sensitivity of the optical information of the specimen 3 that is the sealed sample from being lowered, and to perform highly sensitive measurement.

  In the embodiment of the present invention shown in FIG. 9, the sample 3 sufficient for measurement is positioned on the average not only at the periphery of the bottom 4C of the recess 4 but also at the center of the bottom 4C of the recess 4. When detecting the fluorescence intensity, it is possible to prevent the measurement sensitivity of the optical information of the specimen 3 that is the sealed sample from being lowered, and to perform highly sensitive measurement.

  17 and 18 show another embodiment of the present invention.

  The flat substrate 2 shown in FIG. 17 is made of transparent, for example, plastic, and has a plurality of concave-shaped containers 800. Each container 800 is arranged at intervals along the X direction and the Y direction. The shape of each container 800 has, for example, a square cross section, but is not particularly limited. As shown in FIG. 18, a sample liquid 3S containing the specimen 3 is accommodated in each container 800. Each container 800 of the substrate 2 is tightly covered with the flat cover member 6 so that the sample liquid 3S including the specimen 3 in the container 800 is sealed.

  19 and 20 show still another embodiment of the present invention.

  As shown in FIG. 19, the substrate 2 has a plurality of through holes 850, and a container 880 of the container 870 is disposed in each through hole 850. In the container 880, a sample liquid 3S including the specimen 3 is accommodated. The through hole 850 has a circular cross section, and the container 880 is a cylindrical transparent plastic container, for example.

  One end of the container 880 is an opening 881 and the other end is a closed bottom 882. A male screw portion 883 is formed at one end of the container 880, and the female screw portion of the lid 830 as a cover member can be engaged with the male screw portion 883 to close the opening 881. The lid 830 seals the sample liquid 3S including the specimen 3 in the container 880.

  In addition, the container 880 of the container 870 shown in FIG. 20 accommodates the sample 3 to be measured in the container 880 without being placed on the substrate 2 and applies a centrifugal force to the sample liquid 3S containing the sample 3. Can be collected separately from the bubbles in the container 880 and the optical information of the specimen 3 can be measured.

  In the embodiment of the present invention, at least a part of the concave portion of the substrate is a transparent portion. Further, at least a part of the container is a transparent part.

  In the embodiment of the present invention, the sample liquid 3S including the specimen 3 to be measured is accommodated and sealed in the concave portion as the container of the substrate 2, and the sample liquid 3S including the specimen 3 is collected again in the concave portion. Thus, the optical information of the specimen 3 can be measured from the transparent part of the substrate 2.

  In another embodiment, the container contains and seals the sample liquid 3S containing the specimen 3 to be measured, and the sample liquid 3S containing the specimen 3 is collected again in the container, so that the container is transparent. The optical information of the specimen 3 can be measured from the unit.

  The present invention is not limited to the above-described embodiment, and various modifications can be employed without departing from the scope of the claims.

  For example, the embodiments of FIGS. 10 to 12 and the embodiment of FIG. 13 may be used in combination.

  In the substrate 2 shown in FIG. 3, the protrusions 5 are formed around the edge of the recess 4. However, the present invention is not limited to this, and the protrusions 5 may be omitted as shown in FIGS. The cross-sectional shape of the recess 3 is not limited to the illustrated example, and may be a rectangular shape or other shapes.

  In FIG. 1, as an example, three substrates 2 are disposed on the rotating plate 62, but the present invention is not limited thereto, and one, two, or four or more substrates may be disposed. In the example of FIG. 9, as an example, the two substrates 2 are disposed on the rotating plate 62, but the present invention is not limited thereto, and one or three or more substrates may be disposed.

  The present invention is a field that requires testing, analysis, and analysis of biopolymers of genes, immune systems, proteins, amino acids, and sugars, such as engineering fields, general agricultural sciences such as food, agricultural products, and fishery processing, pharmaceutical fields, hygiene, Applicable to all fields such as health, immunity, plague, genetics and other medical fields, chemistry and biology and other science fields.

It is a figure which shows preferable embodiment of the measuring apparatus of the sample of this invention. It is a figure which shows the DNA chip which is a measuring object. It is a figure which shows the cross-section of a board | substrate. It is a figure which shows the state by which the sample liquid containing a test substance was dispensed in the recessed part from the nozzle. It is a figure which shows the state before mounting a cover member with respect to a board | substrate. It is a figure which shows the state after mounting the cover member with respect to a board | substrate. It is a figure which shows the preparation method of the dispensing specimen containing the measuring method of the sample of this invention. It is a figure which shows the example of the measuring apparatus of a sample. It is a figure which shows the figure which shows another preferable embodiment of the measuring method apparatus of the sample of this invention. It is a figure which shows another embodiment of the measuring method of the sample of this invention. It is a figure which shows the state which positioned the light emission / incidence part in the sample in each recessed part in the example of FIG. It is a figure which shows the state which pushed the light emission / incidence part into the test substance in each recessed part, and concentrated the test substance on the optical fiber end surface. It is a figure which shows another embodiment of the measuring method of the sample of this invention. It is a figure which shows the state by which the sample liquid containing a test substance was unevenly distributed and concentrated on the bottom side of a recessed part as a comparative example. It is a figure which shows the state by which the sample liquid containing a test substance was unevenly distributed and concentrated on the plastic plate side of a recessed part as a comparative example. It is the figure seen from the B arrow in FIG. It is a perspective view which shows another embodiment of this invention. It is sectional drawing which shows a part of embodiment of FIG. It is a figure which shows another embodiment of this invention. It is a perspective view which shows the structure of the container used by embodiment of FIG. It is a figure which shows the state in which the sample liquid containing a test substance is concentrated on the plastic plate side of a recessed part, and the sample liquid containing a test substance decreases in the center part, and is unevenly distributed. It is the figure seen from A arrow in FIG.

Explanation of symbols

1 DNA chip (measurement target)
2 Substrate 3 Specimen 3S Sample liquid 4 Concave 4B Concave opening 4C Concave bottom 6 Cover member 10 Sample measuring device 12 Suction / discharge driving unit 20 Nozzle 60 Rotating device 61 Motor 62 Rotating plate 63 Motor output shaft 64 Rotation center 100 Control unit 250 bubbles

Claims (5)

After accommodating the sample liquid containing the sample to be measured in the concave portion of the substrate on which the concave portion is formed, the sample liquid is sealed in the concave portion by a transparent cover member that is transparent and stretchable.
The cover member has a hydrophilic treatment at least in a portion corresponding to the recess,
The light exit / incident part of the measurement part is applied from the outer surface side of the cover member, and the surface of the cover member on the concave side is pushed in until it comes into contact with the sample. A sample measurement method comprising: measuring the optical information of the specimen by bringing the specimen into contact with the light exit / incident part via the cover member in a state where the specimen is concentrated on the bottom surface side of the specimen.   The inside of the recess is subjected to a hydrophobic treatment, and vibration is applied to the recess where the sample solution is sealed, so that the sample solution containing the sample is placed on the surface of the cover member on the recess side or on the bottom surface side of the recess 2. The sample measuring method according to claim 1, wherein the optical information of the specimen is measured in a state where the samples are gathered together.   The sample measurement method according to claim 1, wherein a plurality of the recesses are formed on the substrate. The sample measurement method according to claim 1 , wherein the bottom of the concave portion is transparent and is subjected to hydrophilic treatment, and optical information of the specimen is measured from the transparent portion. The sample measurement method according to claim 1, wherein the sample is irradiated with excitation light and fluorescence information is measured from the sample.

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