throbber
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`
`SUBSTITUTE SPECIFTCATION — MARKED-UP
`U.S. Patent Application Serial No. 12/810,391
`Attorney Docket No.: 20249.0050USWO
`
`Description
`
`
`
`
`
`SOLUT ON MfiASURHMmNT METHOD AND SOLUTION MEASUREMENT
`
`APPARATUS
`
`
`
`
`
`
`TECHNICAL F 41D Eeehfléeaé—Féelé
`
`10
`
`[0001]
`
`The present
`
`invention relates to a solution
`
`measurement method and a solution measurement apparatus
`
`in which a specimen as a solution to be tested is added
`
`15
`
`to a test piece and is developed thereon and an optical
`
`
`property of the solution at a measured portion of the
`
`test piece is measured to calculate an amount of
`
`substance to be measured in the solution to be tested.
`
`BACKGROUND ART Beekgreuee—Aee
`
`0
`[O 02]
`
`As ar apparatus for measuring a substance to be
`
`measured in a specimen (also called a solution to be
`
`
`
`25
`
`tested)
`
`sach as blood and plasma,
`
`a solution measurement
`
`apparatus has been already known in which a specimen suc_
`
`as blood and plasma is added to a test piece,
`
`the
`
`a substance to
`specimen is developed on the test piece,
`
`be measured is read by using the optical property atter
`
`being immobilized at a predetermined point, and the
`
`concentration (amount) 0:
`
`the substance to be measured is
`
`measured.
`
`[0003]
`
`U) 01
`
`Prior to the explanation of the solution measurement
`
`apparatus, first,
`
`the test piece used in the solution
`
`measurement apparatus will be described below in
`
`

`

`[\J
`
`
`
`accordance with the exploded perspectiv view of the test
`
`piece in FIG.
`
`l4 and the assembly perspective view of the
`
`test piece in FIG. 15. As shown in FIG. 14,
`
`a test piece
`
`10 is configured by bonding a porous substrate 2 that
`
`serves as a development layer for developing the specimen
`
`and a space forming portion 6 that forms a space
`
`for temporarily storing the
`
`1 serving as the base of the
`
`specimen,
`
`to a PET sheet
`
`(solution storage portion)
`
`test piece l0.
`
`On the porous substrate 2,
`
`a labeling
`
`portion 3 is provided which is coated with a labeling
`.C.
`
`substance to be speCi:ically bound to the substance to be
`
`measured in the specimen, and an immobilizing portion 4
`
`serves—as—a—pertéen—te—be—measured on which an antibody
`
`to be specifically bound to the substance to be measured
`
`is immobilized. Further, a PET film 5 is bonded to
`
`10
`
`15
`
`prevent drying of the specimen being developed.
`
`[0004]
`
`
`As shown in FIG. 15,
`
`to the PET sheet
`
`1
`
`the porous substrate 2 is bonded
`
`to increase the strength. Further,
`
`a
`
`
`part of the space forming portion 6 is bonded to the PET
`
`film 5 of the porous substrate 2 or the PET sheet 1.
`
`The
`
`space forming portion 6 is made of a transparent material
`
`such as a PET sheet and has a recessed shape in cross
`
`section. Moreover,
`
`the space forming portion 6 has a
`
`capillary 8 that serves as a solution storage portion for
`
`temporarily storing the added drepped specimen and an air
`
`hole 7 that is formed on a part of the space forming
`
`portion 6.
`
`By adding drepping—+adding+ the specimen to
`
`the capillary 8,
`
`the capillary 8 is filled with the
`
`specimen to the edge of the air hole 7.
`
`The substance to
`
`be measured in the specimen is labeled in the labeling
`
`portion 3 and is developed by capillarity in the porous
`
`substrate 2 along with the specimen. When reaching the
`
`35
`
`immobilizing portion 4,
`
`the substance to be measured is
`
`immobilized and the remainder of the specimen further
`
`

`

`develops downstream.
`
`The labeling substance immobilized
`
`in the immobilizing portion 4 with the substance to be
`
`measured is composed of a substance having a light
`
`absorbing or emitting property.
`
`The optical property of
`
`the solution at the immobilizing portion 4
`
`is measured
`
`and is converted to a concentration by using a
`
`calibration curve,
`
`so that the concentration of the
`
`substance to be measured is determined.
`
`[0005]
`
`10
`
`
`Referring to FIG. 16,
`
`apparatus of the prior art will be described below.
`
`the solution measurement
`
`A
`
`solution measurement apparatus 109 is roughiy classified
`
`into an optical section and a scanning section.
`
`The
`
`scanning section is made up of an attachment 110 for
`
`15
`
`35
`
`setting the test piece 10,
`attachment 110 i (I)
`
`a stage 112 in which the
`
`set, a detection switch 115 for
`
`detecting the insertion of the attachment 110, a feed
`
`screw 114 for scanning the stage 112, and a motor 113 for
`
`rotating the feed screw 114.
`
`up of a laser diode 116,
`
`a beam splitter 119,
`118,
`
`cylindrical
`lens 191, and a signa1 monitor 17?, Light
`
`a
`
`a condenser lens 117, an opening
`
`a front monitor 120,
`
`The optical section is made
`
`emitted from the laser diode 116 is condensed by the
`
`condenser lens 117 and is shaped into a beam having a
`
`predetermined diameter through the opening 118.
`
`The
`
`shaped beam is split by the beam splitter 119. One of the
`
`split beams directly enters the cylindrical lens 121,
`
`is
`
`shaped into an oval, and then is emitted to the test
`
`piece 10.
`
`The other beam is incident on the front monitor
`
`120 made up of a light receiving device such as a photo
`
`diode and the front monitor 120 outputs a current
`
`according to the intensity of light.
`
`of the front monitor 120 is used for adjusting the light
`
`The output current
`
`quantity of the laser diode 116.
`
`The output current is
`
`converted to a voltage by an --V (current-voltage)
`
`
`
`

`

`converter 131 and then is inputted to an error AMP 132.
`
`The error AMP 132 receives an output command value 133
`
`a
`
`(I)
`
`an adjusted value of the laser diode 116 and amplifies a
`
`diff r nc
`botwo n th output command value 133 and the
`
`output of the front monitor 120 to obtain a current
`
`control value.
`
`A current controller 137 passes a current
`
`to the laser diode l16 according to an output
`
`error AMP 132 to keep constant an optical output.
`
`from the
`
`In FIG.
`
`16,
`
`reference numeral 130 denotes a motor controller for
`
`10
`
`controlling the motor 113,
`
`reference numeral 122 denotes
`
`the signal monitor for detecting reflected light from the
`
`test piece 10, and reference numeral 138 denotes an I—V
`
`(current-voltage) converter for converting a current from
`
`the signal monitor l22 to a voltage value.
`
`15
`
`[0006]
`
`Such a solution measurement apparatus is disclosed in
`
`Japanese Patent Laid-Open No. 2003—4743 and so on.
`
`The
`
`following will describe the operations of the solution
`
`measurement apparatus.
`
`The specimen is added dfepped to
`
`the test piece 10 set on the attachment 110. After the
`
`specimen is added drepped,
`
`the attachment 110 is
`
`immediately set in the stage 112,
`
`so that the detection
`
`switch 115 detects the insertion of the attachment 110
`
`and a detection signal is inputted to the motor
`
`In response to the detection signal,
`
`controller 130.
`
`the
`
`motor controller 130 transmits a driving signal
`
`motor l13 to rotate the feed screw 1l4 and the stage l12
`
`to the
`
`is scanned.
`
`
`The feed per revolution of the stage 112 is
`
`determined beforehand and the stage l12 is scanned up to
`
`a position where the outgoing light of the laser diode
`
`116 reaches any position of the test piece 10. At
`
`completion of the movement of the stage 112,
`
`the laser
`
`the
`
`diode 116 is driven to emit light to the test piece 10
`
`and the reflected light is received by the signal monitor
`
`35
`
`122.
`
`
`
`FIG. 17 is a time—series graph showing the output 0:
`
`

`

` G)
`the signal monitor 122 at this point. As shown in F:
`
`l...) \J \
`
`when the specimen has not reached a laser irradiation
`
`position on the test piece 10, reflected light from the
`
`test piece 10 is directly used as a signal monitor output.
`
`Wh n the sp cim n r ach 3 th
`1as r irradiation position
`
`containing the immobilizing portion 4,
`
`on the specimen.
`
`
`
`signal monitor 122 is reduced by the absorption of light
`
`3y detecting a reduction of the monitor
`
`the Oltput of the
`
`
`
`10
`
`15
`
`output signal
`
`thus,
`
`laser irradiation position is detected.
`
`the light of the laser diode 116
`
`measurement apparatus,
`
`the arrival of the specimen at
`
`in the solution
`
`the
`
`is emitted up to an end of the porous substrate 2.
`
`[0007]
`
`After it is detected that the specimen has reached
`
`the position,
`
`the specimen is sufficiently developed for
`
`a predetermined standby time, and then measurement is
`
`started on a solution at the immobilizing [{the]} portion
`
`te—be—measured.
`
`The motor 113 is driven by the motor
`
`controller 130 and the outgoing light of the laser diode
`
`116 is scanned on the test piece 10.
`
`A value obtained by
`
`performing LOG conversion on the output of the front
`
`monitor “20 by a LOG converter 134 and a value obtained
`
`
`
`by performing LOG conversion on the output of the signal
`
`monitor 122 by a LOG converter 135 are calculated by an
`
`so that an absorbance signal of the
`
`the completion of scanning
`
`arithmetic unit 136,
`
`test piece 10 is obtained. At
`
`o:
`
`the test piece 10,
`
`the stage 112 is moved to a
`
`position where the attachment 110 can be removed, and
`
`then the measuring operation is completed.
`
`[0008]
`
`
`In this case, when the amount of the added drepped
`
`specimen is insufficient or in the event of an abnormal
`
`flow causing the specimen to clog in the test piece
`
`0,
`
`the specimen does not flow to the end of the porous
`
`35
`
`substrate 2,
`
`so that the specimen does not reach the
`
`

`

`light irradiation position of the laser diode 116.
`
`In
`
`this case, it is decided after a predetermined time that
`
`the specimen has abnormally flowed.
`
`
`A user is notified of
`
`
`
`the abnormal state and the measuring operation is
`
`forcibly terminated.
`
`SUMMARY OF THE INVENTTON Bésclosure—ef—the—énventien
`
`
`Problems to be Solved by the fnvention
`
`10
`
`[0009]
`
`
`
`fn the configuration of the solution measurement
`
`apparatus of the prior art, however, when there is a time
`
`lag between the adding drepping of the specimen to the
`
`test piece 10 and the setting of the test piece 10 in the
`
`15
`
`solution measurement apparatus,
`
`the specimen has passed
`
`
`
`the laser irradiation position upon detection and thus
`
`the flow of the specimen cannot be detected.
`
`
`
`[0010]
`
`uniform,
`
`Further, since the viscosities of specimens are not
`
`the flow rates vary with the viscosities of the
`
`specimens during any time period after the specimens are
`
`detected at the laser irradiation position.
`
`In other
`
`words,
`
`a specimen having a low viscosity is quickly
`
`developed, whereas a specimen having a high viscosity is
`
`slowly developed. This factor varies the amounts of the
`
`specimens flowing through the immobilizing portion 4 of
`
`the test piece "0, and thus measurements started based on
`
`development states at the front position of the developed
`
`
`
`rent m asurcmont results
`portion of a solution cause di
`
`
`
`and reduce measurement accuracy.
`
`[0011]
`
`The present
`
`invention has been devised to solve the
`
`problems of the prior art. An object of the present
`
`35
`
`invention is to provide a solution measurement method and
`
`a solution measurement apparatus which can satisfactorily
`
`

`

`\J
`
`
`detect the flow of a solution to be tested as a specimen
`
`and can accurately calculate the amount of a substance to
`
`be measured in a state in which a uniform amount of the
`
`solution to be tested is developed.
`
`Means for Solving the Problems
`
`[0012]
`
`
`In order to solve the problems of the prior art, a
`
`solution measurement method of the present invention in
`
`10
`
`which a solution to be tested is temporarily stored in the
`
`solution storage portion of a test piece after the solution
`
`is when added to the test piece,
`
`the solution to be tested
`
`is transferred from the solution storage portion to the
`
`15
`
`development layer and is developed on the development
`
`of the test piece érem—the—selutiefi—sterage—pertien,
`
`r
`
`laye
`
`the
`
`development
`
`layer having an immobilizing {{a]] portion te—
`
`be—measared, and the amount of a substance to be measured
`
`in the solution to be tested is calculated by measuring th
`
`e
`
`optical property of the solution at the immobilizing
`
`portion—te—be—measured,
`
`
`the method including: measuring the
`
`solution at the immobilizing portion te—be—measared,
`
`in
`.1.
`response to a reduction of the solution to be tested so a
`
`predetermined amount or less in the solution storage
`
`portion; and calculating the amount of the substance
`
`H 0
`
`be
`
`measured in the solution to be tested, based on the
`
`measured value.
`
`[00l3]
`
`According to this method, it is possible to detect
`
`that a certain amount of the solution to be tested has
`
`
`flown from the solution storage portion to the
`
`immobilizing portion at which the solution is to be
`
`measured on the development layer, and accurately
`
`calculate the amount of the substance to be measured in
`
`
`state in which substantially a uniform amount of the
`
` solution to be tested is developed.
`
`35
`
`a
`
`

`

`[0014]
`
`The solution measurement method of the present
`
`invention further includes: measuring a flowing time from
`
`the addition of the solution to be tested to the test
`
`
`piece to the reduction of the solution to be tested in
`
`the solution storage portion to the predetermined amount
`
`or less; waiting a time period corresponding to the
`
`flowing time after the solution to be tested in the
`
`solution storage portion reduces to the predetermined
`
`amount or less; and calculating the amount of the
`
`
`
`substance to be measured in the solution to be tested,
`
`
`
`after the time period and based on the measured value of
`
`the solution at the immobilizing portion—te—be—measured.
`
`[0015]
`
`A solution measurement method of the present invention
`
`in which a solution to be tested is temporarily stored in
`A—
`
`the solution storage portion of a L st pi c aft r the
`
`solution is when added to the test piece,
`
`the solution to
`
`be tested is transferred from the solution storage portion
`
`to the development layer and is developed on the
`
`development layer of the test piece érem—the—selutien—
`
`the development layer having an
`
`t
`
`c
`
`i -,
`
`10
`
`15
`
`immobilizing {{a]] portion te—be—measured, and the amount
`
`of a substance to be measured in the solution to be tested
`
`is calculated by measuring the optical property of the
`
`solution at the immobilizing portion te—be—meaeured,
`
`the
`
`method including: measuring the initial storage amount of
`
`the solution to be tested in the solution storage portion
`
`
`of the test piece, after when the solution to be tested is
`
`added to the test piece mounted at a predetermined mounting
`
`location or when the test piece on which the solution to be
`
`tested has been added is mounted at the predetermined
`
`mounting location; measuring the storage amount of the
`
`solution storage portion also after the solution to be
`
`35
`
`tested is added; measuring the optical property of the
`
`

`

`solution at the immobilizing portion Ee—be—measared,
`
`in
`
`response to a reduction of the solution to be tested from
`
`the initial storage amount by a predetermined amount
`
`in the
`
`solution storage portion; and calculating, based on the
`
`5 measured value,
`
`the amount of the substance to be measured
`
`in the solution to be tested.
`
`[0016]
`
`According to this method, it is possible to detect
`
`that a predetermined amount of the solution to be tested
`
`has flown from the solution storage portion to the
`
`10
`
`immobilizing portion at which the solution is to be
`
`measured on the development layer, and accurately
`
`calculate the amount of the substance to be measured in a
`
`state in which a uniform amount of the solution to be
`
`15
`
`tested is developed.
`
`[0017]
`
`
`The solution measurement method of the present
`
`invention further includes: measuring a flowing time from
`
`the addition of the solution to be tested to the test
`
`20
`
`
`piece to the reduction of the solution to be tested in
`
`the solution storage portion by the predetermined amount;
`
`waiting a time period corresponding to the flowing time
`
`
`after the reduction of the solution to be tested in the
`
`25
`
`
`
`solution storage portion by the predetermined amount; and
`
`calculating the amount of the substance to be measured in
`
`the solution to be tested, after the time period and
`
`based on the measured value of the solution at the
`
`immobilizing portion—te—be—measured.
`
`[0018]
`
`30
`
`The solution measurement method of the present
`
`invention further includes: measuring the initial storage
`
`amount of the solution to be tested in the solution
`
`storage portion of the test piece, when the solution to
`
`b
`
`e tested is added to the test piece mounted at a
`
`35
`
`predetermined mounting location or when the test piece on
`
`

`

`which the solution to be tested has been added is mounted
`
`at the predetermined mounting location; and performing at
`
`least one of a measurement terminating operation and a
`
`warning operation when the initial storage amount of the
`
`solution to be tested is smaller than predetermined
`
`initial storage setting.
`
`[0019]
`
`Thus when the solution to be tested is added to the
`
`test piece mounted in a solution measurement apparatus or
`
`10
`
`when the test piece on which the solution to be tested
`
`has been added is mounted in the solution measurement
`
`apparatus, it is possible to prevent measurement
`
`abnormal state with an insufficient initial storage
`
`thereby preventing erroneous measurement of the
`
`amount,
`
`in an
`
`15
`
`amount of the substance to be measured.
`
`[0020]
`
`Further, according to the solution measurement method
`
`
`of the present invention,
`
`the test piece is a test piece
`
`for chromatography.
`
`[0021]
`
`A solution measurement apparatus of the present
`
`invention in which a solution to be tested is temporarily
`
`stored in the solution storage portion of a test piece
`
`when added to the test piece,
`
`the solution to be tested
`
`is developed on the development layer of the test piece
`
`from the solution storage portion, and the amount of a
`
`substance to be measured in the solution to be tested is
`
`calculated by measuring the optical property of the
`
`solution at a predetermined portion of te—be—measufed—en
`
`
`
`the development layer of the test piece,
`
`the solution
`
`measurement apparatus including: an imaging device for
`
`imaging the solution at
`
`the predetermined portion te—be—
`
`measured—and the solution storage portion of the test
`
`piece; a solution amount detector for detecting, based on
`
`imaging information,
`
`the amount of the solution to be
`
`35
`
`

`

`tested in the solution storage portion; and a controller
`
`for measuring the solution at the immobilizing portion—te—
`1
`
`c
`
`.c c
`
`,
`
`in response to a reduction of the solution
`
`to be tested to a predetermined amount or less in the
`
`
`
` solution storage portion, and calculating, based on the
`
`5
`
`solution storage portion or a reduction of the solution
`
`to be tested by the predetermined amount or more in the
`
`measured value,
`
`
`the amount of the substance to be
`
`measured in the solution to be tested.
`
`10
`
`[0022]
`
`
`With this configuration, it is possible to detect
`
`that a certain amount or a predetermined amount of the
`
`solution to be tested has flown from the solution storage
`
`portion to the immobilizing portion at which the solution
`
`is to be measured on the development layer, and
`
`15
`
`accurately calculate the amount of the substance to be
`
`
`measured in a state in which substantially a uniform
`
`amount of the solution to be tested is developed.
`
`[0023]
`
`20
`
`c
`
`The solution measurement apparatus Ol
`
`invention further includes an illuminator for
`
`the present
`
`illuminating the test piece with measurement light; and a
`
`light receiver for receiving the reflected light of the
`
`measurement light having illuminated the test piece.
`
`25
`
`[0024]
`
`According to the solution measurement apparatus of
`
`the illuminator is one of an LED,
`
`the present invention,
`
`an LD, and a lamp.
`
`[0025]
`
`30
`
`According to the solution measurement apparatus of
`
`the present invention,
`sensor.
`
`the light receiver is an image
`
`[0026]
`
`

`

`
`According to the solution measurement apparatus of
`
`the test piece is a test piece for
`
`the present invention,
`
`chromatography.
`
`5
`
`
`Advantage of the Invention
`
`[0027]
`
`According to a solution measurement method and a
`
`solution measurement apparatus of the present
`
`invention,
`
`it is possible to measure a substance to be measured in
`
`10
`
`15
`
`in a state
`an immobilizing
`
`
`in which a uniform amount or substantially a uniform
`
`amount of a solution to be tested flows from a solution
`
`,...|
`
`[a
`
`L...‘
`
`] portion te—be—measured,
`
`storage portion,
`
`thereby improving measurement accuracy
`
`for measuring the solution.
`
`
`
`
`
`BRTHF DHSCR PT ON OF IHH DRAWINGS Préei—Deser4ptéen—ef—
`
`the—Brawifigs
`
`[0028]
`
`FIG.
`
`1 schematically shows a solution measurement
`
`apparatus according to an embodiment of the present
`
`invention;
`
`FIG.
`
`2 is a flowchart showing a solution measurement
`
`method according to a first embodiment of the present
`
`invention;
`
`FIG.
`
`3 shows an image obtained by an image sensor
`
`before adding of a specimen dreppifig according to the
`
`first embodiment of the present invention;
`
`FIG.
`
`4 shows a capillary image obtained by the image
`
`sensor before adding of a specimen drepping, and an image
`
`sensor output according to the :irst embodiment of the
`
`
`
`present invention;
`
`FIG.
`
`5A shows a capillary image obtained immediately
`
`
`after adding of a specimen drepping according to the
`
`35
`
`first embodiment of the present invention;
`
`

`

`FIG.
`
`5B shows a capillary image obtained after a
`
`I
`predetermined time since adding of a specimen drepping
`
`according to the first embodiment of the present
`
`invention;
`
`FIG.
`
`6 shows an amount of a specimen in a capillary
`
`relative to an elapsed time after the adding drepping of
`
`
`the specimen according to the first embodiment of the
`
`present
`
`invention;
`
`FIG.
`
`7 shows a capillary image obtained by the image
`
`
`
`10
`
`sensor when the specimen is added drepped, and an image
`
`sensor output according to the first embodiment of the
`
`present
`
`invention;
`
`FIG.
`
`
`8 shows a flowing state of a specimen on a test
`
`piece according to a second embodiment of the present
`
`15
`
`invention;
`
`FIG.
`
`9 shows an optical property measuring process
`
`according to the second embodiment of the present
`
`invention;
`
`FIG.
`
`10 shows an image sensor output at a monitor
`
`point according to the second embodiment of the present
`
`invention;
`
`FIG. ll shows a drop detecting process according to
`
`third embodiment of the present invention;
`
`a
`
`FIG. 12 shows a specimen amount detecting process
`
`according to a fourth embodiment of the present
`
`invention;
`
`
`
`FIG. 13 shows a flow rate of a specimen relative to
`
`an elapsed time after adding of a specimen drepping
`
`according to the fourth embodiment of the present
`
`invention;
`
`
`FIG. 14 is an explod d p rsp ctiv vi w showing a
`
`test piece of a solution measurement apparatus according
`
`to the prior art;
`
`

`

`FIG.
`
`15 is an assembly perspective view showing the
`
`test piece of the solution measurement apparatus
`
`ccording to the prior art;
`
`FIG. 16 is a schematic diagram showing the solution
`
`5
`
`measurement apparatus according to the prior art; and
`
`FIG. 17 shows a signal monitor output of the solution
`
`
`
`measurement apparatus according to the prior a
`
`
`
`
`
`10
`JETA LFD DRSCRTPT"ON OF THE INVENTION Best—Meée—§e¥—
`
`[0029]
`
`
`in the present disclosure,
`
`
`a change of the surface
`
`15
`
`area of a solution stored in a solution storage portion
`
`of a test piece reflects a change of the volume of the
`
`solution in the solution storage portion.
`
`
`
`A solution measurement apparatus and a solution
`
`measurement method according to embodiments of the
`
`invention will be specifically described below
`
`present
`
`along with the accompanying drawings.
`
`A test piece used
`
`in the solution measurement apparatus and the solution
`
`measurement method according to the embodiments of the
`
`invention is configured as in the solution
`
`present
`
`measurement apparatus of the prior art. Constituent
`
`elements having the same functions will be indicated by
`
`
`same rc; r nc
`num rals.
`
`th
`
`(First Embodiment)
` FIG.
`
`1 schematically shows a solution measurement
`
`apparatus according to an embodiment of the present
`
`the configuration of the solution
`
`invention. First,
`
`measurement apparatus will be described below.
`
`The
`
`solution measurement apparatus includes a stage 12 acting
`
`as a test piece holder for positioning and setting a test
`
`piece 10 on which a specimen is added +drepped+ as a
`
`35
`
`solution to be tested,
`
`a detection switch 15 acting as a
`
`

`

`test piece mounting state detector for detecting the
`
`insertion of the test piece 10 into the stage 12,
`
`a light
`
`source 21 acting as an illuminator made up of an LED
`
`(light—emitting diode), an LD (laser diode), or a lamp
`
`(for passing current through an electric wire such as a
`
`
`filament
`
`to emit light) to illuminate the test piece 10,
`
`a front monitor 20 for monitoring the output light of the
`
`light source 21, an image sensor 22 that is made up of an
`
`10
`
`image pickup device such as a CCD or a C-MOS and acts as
`
`an imaging device for imaging the test piece 10,
`
`a
`
`diaphragm 23 for adjusting reflected light from the test
`
`a condenser lens 24 for forming an image of the
`
`piece 10,
`
`test piece 10 on the image sensor 22, an image sensor
`
`controller 26, an image processor 30, and a controller
`
`15
`
`(not shown).
`
`[0030]
`
`The following will describe the operations of the
`
`light source 21 and the image sensor 22.
`
`In this
`
`mechanism, an error between the output of the front
`
`monitor 20 and an output command value 33 is amplified by
`
`
`
`an error AMP 32 and is inputted to a current controller
`
`37, and the driving current of the light source 21 is
`
`controlled to adjust an amount of light emitted to the
`
`test piece 10.
`
`The error AMP 32 further receives a
`
`measurement start signal 34 synchronized with the
`
`detection switch 15 for detecting the insertion of the
`
`test piece 10 into the stage 12, and the light source 21
`
`is not
`
`turned on unless the test piece 10 is set in the
`
`stage 12.
`
`The image sensor 22 is driven by the image
`
`sensor controller 26 to obtain and transfer data, and the
`
`data is outputted as image data to the image processor 30.
`
`Further,
`
`the image sensor controller 26 does not operate
`
`unless the measurement start signal 34 is inputted.
`
`[0031]
`
`

`

`Referring to the flowchart of FIG. 2,
`
`the following
`
`will describe the measuring operation processes (solution
`
`measurement method) of
`
`A process of measurement
`
`the solution measurement apparatus.
`
`is broadly divided into three
`
`10
`
`15
`
`processes of a drop (an added solution) detecting process,
`
`a specimen amount (solution amount) detecting process,
`
`and an optical property measuring process.
`
`
`in the drop
`
`detecting process, it is detected that a specimen as a
`
`solution to be tested has been added drepped—+adéed+ to
`
`the test piece 10, and then a measuring operation is
`
`started.
`
`
`in the specimen amount detecting process, an
`
`amount of the specimen in a capillary 8 serving as a
`
`solution storage portion is measured to determine
`
`measurement start timing.
`
`
`in the optical property
`
`measuring process,
`
`the test piece 10 is imaged on which a
`
`predetermined amount of the specimen has flown, and the
`
`roperty of the solution at an immobilizing
`
`optical
`
`portion 4 seryifig—as—a—pertiefi—te—be—measfired—is measured
`
`and is converted to a concentration (amount) of a
`
`substance to be measured in the specimen.
`
`[0032]
`
`These processes will be sequentially described below.
`
`First,
`
`the test piece 10 is set in the stage 12 before
`
`the specimen is added drepped. When the detection switch
`
`15 detects that the test piece 10 has been set,
`
`is outputted from the error AMP
`
`measurement start signal
`
`the
`
`32 to turn on the light source 21 and the image sensor
`
`controller 26 is driven to image the test piece 10. This
`
`imaging operation obtains an image shown in FIG. 3.
`
`By
`
`using this image,
`
`the adding drepping of the specimen on
`
`the test piece 10 is detected.
`
`In order to detect the
`
`adding drepping of the specimen, an image at the point of
`
`is recognized in the image of FIG. 3.
`
`forming the space of the
`
`the capillary 8
`
`A
`
`space forming portion
`
`0‘)
`
`35
`
`p
`ca illar
`
`Y
`
`_
`8 is made of a transparent material such as a
`
`

`

`PET sheet,
`
`’1
`so that an image of the capillary a can be
`
`obtained through the space forming portion 6.
`
`[0033]
`
`The following will describe a method of cutting out
`
`
`the image of the capillary 8.
`The image is cut out before
`
`the specimen is added dropped.
`
`[0034]
`
`In a first method of cutting out
`
`the image of the
`
`10
`
`capillary 8,
`
`the region of the capillary 8 is specified
`
`beforehand as the coordinates of an image of the image
`
`sensor. Since the test piece 10 is positioned and mounted
`n,
`by the stage la,
`
`the coordinates on the image sensor
`0
`image of the capillary o can be set so as to be always
`
`15
`
`aligned with the stage l2. Thus the image of the region
`
`
`of the capillary 8 is specified and cut out beforehand
`
`according to the coordinates on the image sensor image.
`
`[0035]
` In a second method, an image sensor output is stored
`
`and the image of the capillary 8 is obtained from the
`
`pattern of an output
`
`image.
`
`A region for storing the
`
`
`image sensor output is specified beforehand as
`
`coordinates on an image sensor image.
`
`The region
`
`specified at this point is larger than in the first
`
`method and can sufficiently contain the capillary 8.
`
`In this
`
`4 shows an image cut out by the second method.
`
`FIG.
`
`
`
`case,
`
`the region of the space forming portion 6 is cut
`
`out as an image. First, an imaging extraction line B—B’
`
`is set substantially at
`
`the center of the width direction
`
`(also called a shorter direction) of the test piece 10
`
`and in the longitudinal direction (also called a longer
`
`direction) of the test piece 10, and an image sensor
`
`output is extracted on the imaging extraction line B—B’.
`
`In this case, since a labeling substance is applied to a
`
`labeling portion 3,
`
`light is absorbed and the image
`
`35
`
`sensor output decreases.
`
`A porous substrate 2
`
`
`is made of
`
`

`

`a white material or a material not absorbing light,
`9
`that light is reflected on the porous substrate _ and the
`
`so
`
`image sensor output increases.
`The space forming portion
`,c
`
`
`
`
`6 is made of a transparent resin and thus hardly a fects
`
`the image sensor output. An air hole 7
`
`forming a through hole on the space forming portion 6 and
`
`is provided by
`
`thus light partially reflects on the edge of the air hole
`
`[0036]
`
`IO
`
`15
`
`Therefore,
`
`the image sensor output on the imaging
`
`extraction line B-B’ has characteristics indicated by the
`
`lower region 0; FIG. 4.
`
`fluctuations in image sensor output between a region (I)
`
`having the air hole 7 and a convex region (2) of the
`
`In FIG. 4, by reading
`
`image sensor output appearing on the corresponding end
`
`(the right end (adding dreppifig side) of FIG.
`
`4) of the
`
`test piece 10,
`
`the specimen in the capillary 8
`
`in the
`
`longer direction on the test piece 10 is located in—the—
`
`'ic i '. Next,
`
`in the shorter direction of the
`
`test piece 10, an imaging extraction line C-C’
`
`is set so
`
`as to contain at least a region where the capillary 8 is
`
`provided. An image sensor output on the imaging
`
`extraction line C-C'
` FIG. 4.
`
`The image sensor output on the imaging extraction
`
`
`is indicated in the right region of
`
`line C-C’ changes at boundaries (3) and (4) between the
`
`capillary 8 and a PET sheet I.
`
`The specimen of the
`
`capillary 8
`
`in the shorter direction on the test piece 10
`
`is located in—the—sherter—direetiefi by reading
`
`fluctuations in image sensor output at the boundaries (3)
`
`
`In this way,
`in
`
`the specimen in the capillary 8
`
`and (4).
`
`the longer direction and the shorter direction on the
`
`test piece 10 is located in—the—lenger—direetien—and—the—
`
`sherter—direetien. During the location of the capillary 8,
`C .
`
`icult to determine the points of the
`
`when it is dif:
`
`35
`
`regions (1)
`
`to (4)
`
`shown in FIG. 4,
`
`the brightness and
`
`

`

`
`contrast of the image sensor output
`
`image are adjusted
`
`beforehand,
`
`so that the region of the capillary 8 can be
`
`easily specified.
`
`[0037]
`
`At
`
`the completion of the cutting out of the image of
`
`the capillary 8, an image sensor output is extracted at a
`
`specific point
`
`(location) on the image as will be described
`
`
`below. The operations from the cutting out of the image of
`
`10
`
`the capillary 8
`
`to the extraction of the image sensor
`
`output at the specific point are repeated until the image
`
`sensor output changes. Since the specimen has a light
`
`absorbing property,
`
`the image sensor output decreases when
`
`the specimen is added dfepped to the capillary 8. A time at
`
`which the image sensor output changes is regarded as a
`
`15
`
`specimen adding dpeppdng time. FIG.
`
`5A is an image of a
`
`state of the capillary 8
`
`immediately after the specimen is
`
`the capillary 8 is filled
`added dfepped. At this point,
`
`
`
`
`with a specimen X. FiG. 55 shows a state of the capillary 8
`
`after a predetermined time since the specimen X has been
`
`added dpepped. The added dpepped specimen X develops on the

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