throbber
+3
`
`SUBSTITUTE SPECIFICATION — MARKED-UP
`U_S. Patent Application Serial No. 12/810,391
`Attorney Docket No.: 20249.0050USWO
`
`Description
`
`
`
`
`
`
`SOLUTION MEASUREMENT METHOD AND SOLUTION MEASUREMENT
`
`APPARATUS
`
`
`
`
`
`
`TECHNICAL FIELD Peekhes+eatFete
`
`fooo1]
`
`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 BeekeroussAse
`
`As an apparatus for measuring a substance to be
`
`measured in a specimen (also called a solution to be
`
`
`
`25
`
`tested)
`
`such as blood and plasma,
`
`a solution measurement
`
`apparatus has been already known in which a specimen such
`
`as blood and plasma is added to a test piece,
`
`the
`
`specimen is developed on the test piece, a substance to
`
`
`be measured is read by using the optical property after
`
`30
`
`being immobilized at a predetermined point, and the
`
`concentration (amount) of the substance to be measured is
`
`measured.
`
`[0003]
`
`Prior to the explanation of the solution measurement
`
`apparatus, first,
`
`the test piece used in the solution
`
`Oo an
`
`measurement apparatus will be described below in
`
`

`

`ho
`
`
`
`accordance with the exploded perspective
`view of the test
`
`piece in FIG.
`
`14 and the assembly perspective view of the
`
`test piece in FIG.
`
`i5. 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 10.
`
`On the porous substrate 2,
`
`a labeling
`
`10
`
`portion 3 is provided which is coated with a labeling
`"os
`
`ficaliy bound to the substance to be
`
`substance to be sp
`
`measured in the specimen, and an immobilizing portion 4
`
`seryes—asapertienopemeaseuted on which an antibody
`
`to be specificaliy bound to the substance to be measured
`
`15
`
`is immobilized. Further, a PET film 5 is bonded to
`
`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 € has a
`
`capillary 8 that serves as a solution storage portion for
`
`temporarily storing the added dressed specimen and an air
`
`hole 7 that is formed on a part of the space forming
`
`portion 6.
`
`By adding drepseingeteddies} the specimen to
`
`the capiliary 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
`
`immobilizing portion 4,
`
`the substance to be measured is
`
`immobilized and the remainder of the specimen further
`
`35
`
`

`

`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.
`
`10
`
`[G005]
` Referring to FIG.
`
`apparatus of the prior art will be described below.
`
`the solution measurement
`
`i6,
`
`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
`
`setting the test piece 10,
`
`a stage 1122
`
`in which the
`
`attachment 110 is 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,
`
`eylindrical
`lens 121, and a signal monitor i122. 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 cutputs a current
`
`The output current
`according to the intensity of light.
` of the front monitor 120 is used for adjusting the Light
`
`quantity of the laser diode 116.
`
`The output current is
`
`35
`
`converted to a voltage by an I-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
`
`~
`
`an adjusted value of the laser diode 116 and amplifies a
`
`difference
`between the output command value 133 and the
`
`output of the front monitor 120 to obtain a current
`
`control value.
`
`A current controiler 137 passes a current
`
`to the laser diode 116 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 122 to a voltage value.
`
`15
`
`fo0o6]
`
`Such a solution measurement apparatus is disciosed 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 deesped to
`
`the test piece 10 set on the attachment 110. After the
`
`specimen is added d¥eesped,
`
`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 signai
`
`motor 113 to rotate the feed screw 114 and the stage i12
`
`to the
`
`is scanned.
`
`
`The feed per revolution of the stage 112 is
`
`determined beforehand and the stage 112 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 of
`
`

`

` Q
`the signal monitor 122 at this point. As shown in FI
`
`bes ~] ~
`
`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.
`
`When the specimen reaches the
`laser irradiation position
`
`containing the immobilizing portion 4,
`
`the output of the
`
`Signal monitor 122 is reduced by the absorption of light
`
`By detecting a reduction of the monitor
`
`
`
`
`
`on the specimen.
`
`output signal
`
`thus,
`
`10
`
`15
`
`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 cf the porous substrate 2.
`
`fOOO07]
`
`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 [fthe]] portion
`
`tebe-meastred.
`
`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 120 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
`
`of 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.
`
`[G008]
`
`
`In this case, when the amount of the added d*eepeed
`
`specimen is insufficient or in the event of an abnormal
`
`flow causing the specimen to clog in the test piece
`
`109,
`
`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 i16.
`
`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 INVENTION B+setesure—eftheterernttieon
`
`
`Problems to be Solved by the Invention
`
`10
`
`[O009]
`
`
`
`In the configuration of the solution measurement
`
`apparatus of the prior art, however, when there is a time
`
`lag between the adding deeppise 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.
`
`
`
`fO010]
`
`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 19, and thus measurements started based on
`
`development states at the front position of the developed
`
`
`
`portion of a solution cause different measurement results
`
`
`
`and reduce measurement accuracy.
`
`fOOi1]
`
`The present
`
`invention has been devised to solve the
`
`problems of the prior art. An object of the present
`
`invention is to provide a solution measurement method and
`
`a solution measurement apparatus which can satisfactorily
`
`35
`
`

`

`~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
`
`[0022]
`
`
`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
`
`iswhen 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 #remtheselitticsstoragepertics,
`
`the
`
`15
`
`development
`
`layer having an immobilizing [{a]] portion =e—
`
`be-measueed, 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—tebe-meastuted,
`
`
`the method including: measuring the
`
`solution at the immobilizing portion tebe-measteed,
`
`in
`
`response to a reduction of the solution to be tested to a
`
`predetermined amount or less in the solution storage
`
`portion; and calculating the amount of the substance to be
`
`measured in the solution to be tested, based on the
`
`measured value.
`
`£0013]
`
`According to this method, it is possibie to detect
`
`that a certain amount of the soluticn to be tested has
`
` flown from the solution storage portion to the
`
`immobilizing portion at which the sclution is to be
`
`measured on the development layer, and accurately
`
`calculate the amount of the substance to be measured in a
`
` solution to be tested is developed.
`
`
`state in which substantially a uniform amount of the
`
`35
`
`

`

`10
`
`15
`
`[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—measteecd.
`
`£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 test piece after the
`
`solution is wren 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 frem-the—setbticn—
`
`+
`
`2
`
`ton,
`
`the development layer having an_
`
`immobilizing [fa]] portion te—-ewe—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-measeeed,
`
`the
`
`method including: measuring the initial storage amount of
`
`the solution to be tested in the solution storage portion
`
`
`of the test piece, after whem 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 te—be-measeeed, 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
`
`measured value,
`
`the amount of the substance to be measured
`
`in the solution to be tested.
`
`[C016]
`
`According to this method, it is possibie 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 ina
`
`state in which a uniform amount of the solution to be
`
`15
`
`tested is developed.
`
`[GO17]
`
`
`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 by the predetermined amount;
`
`waiting a time period corresponding to the flowing time
`
` after the reduction of the solution to be tested in the
`
`
`
`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—tebe-measttred.
`
`foots]
`
`The solution measurement method of the present
`
`invention further includes: measuring the initial storage
`
`amount of the soiution to be tested in the solution
`
`storage portion of the test piece, when the solution to
`
`be
`
`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 possibie 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.
`
`fO021]
`
`A solution measurement apparatus of the present
`
`invention in which a soiution to be tested is temporarily
`
`stored in the solution storage portion of a test piece
`
`when added to the test piece,
`
`the scoiution to he 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+ebemeasuredof
`
`
`
`the development layer of the test piece,
`
`the solution
`
`measurement apparatus including: an imaging device for
`
`imaging the solution at
`
`the predetermined portion =6+be—
`
`measived-—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—-e.e—
`
`CReas
`
`,
`
`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
`
`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
`
`15
`
`isto be measured on the development layer, and
`
`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]
`
`co
`
`The solution measurement apparatus of
`
`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.
`
`[0024]
`
`According to the solution measurement apparatus of
`
`the illuminator is one of an LED,
`
`the present invention,
`
`an LD, and a liamp.
`
`[0025]
`
`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.
`
`
`Advantage of the Invention
`
`[O027]
`
`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
`
`in a state
`an immobilizing [[aj] portion #e—be-—meastred,
`
`
`in which a uniform amount or substantially a uniform
`
`amount of a solution to be tested flows from a solution
`
`storage portion,
`
`thereby improving measurement accuracy
`
`for measuring the solution.
`
`10
`
`15
`
`
`
`
`
`BRIEF DESCRIPTION OF THE DRAWINGS BetetBbeseristicnef
`
`the_Deawings
`
`[0028]
`
`FIG.
`
`2 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 deeppisg 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 dreppine, and an image
`
`sensor output according to the first embodiment of the
`
`present invention;
`
`FIG.
`
`5A shows a capillary image obtained immediately
`
`
`after adding of a specimen deeppiseg according to the
`
`35
`
`first embodiment of the present invention;
`
`

`

`FIG.
`
`5B shows a capillary image obtained after a
`
`predetermined time since adding of a specimen dreppine
`
`according to the first embodiment of the present
`
`invention;
`
`6 shows an amount of a specimen in a capillary
`FIG.
`relative to an elapsed time after the adding deepeing of
`
`
`the specimen according to the first embodiment of the
`
`present
`
`invention;
`
`FIG.
`
`7 shows a capillary image obtained by the image
`
`10
`
`ensor when the specimen is added deepped, 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.
`
`$3 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.
`
`i1 shows a drop detecting process according to a
`
`third embodiment of the present invention;
`
`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 exploded perspective
`view 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
`
`eccording to the prior art;
`
`FIG. 16 is a schematic diagram showing the solution
`
`measurement apparatus according to the prior art; and
`
`i7 shows a signal monitor output of the solution
`
`FIG.
`
`
`
`measurement apparatus according to the prior art.
`
`
`
`
`
`
`10
`DETATLED DESCRIPTION OF THE INVENTION Best—Mede—fos—
`
`[0029]
`
`
`
`In the present disclosure, a change of the surface
`
`area of a solution stored in a soiution storage portion
` of a test piece reflects a change of the volume of the
`
`15
`
`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 pricr art. Constituent
`
`elements having the same functions will be indicated by
`
`
`same reference
`numerals.
`
`the
`
`(First Embodiment)
` FIG.
`
`1 schematicaliy 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,
`
`source 21 acting as an illuminator made up of an LE
`
`a light
` Oo
`
`{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
`
`image pickup device such as a CCD or a C-MOS and acts as
`
`an imaging device for imaging the test piece 10,
`
`a
`
`10
`
`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).
`
`[GO36]
`
`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 uniess 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
`
`wili describe the measuring operation processes (solution
`
`measurement method) of
`
`A process of measurement
`
`the solution measurement apparatus.
`
`is broadiy divided into three
`
`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 dresppedtadded to
`
`10
`
`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
`
`15
`
`measuring process,
`
`the test piece 10 is imaged on which a
`
`predetermined amount of the specimen has flown, and the
`
`property of the solution at an immobilizing
`
`optical
`
`portion 4 sesevis¢-es-—perticontebemeasttecdis 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 deeppee. 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 deeppise of the specimen on
`
`the test piece 10 is detected.
`
`In order to detect the
`
`adding deeppiss of the specimen, an image at the point of
`
`is recognized in the image of FIG. 3.
`
`space forming portion 6 forming the space of the
`
`the capillary 8
`
`A
`
`35
`
`capillary
`Pp
`
`y
`
`8 is made of a transparent material such as a
`k
`
`

`

`PET sheet,
`
`c
`so that an image of
`
`ga
`the capillary 8 can be
`
`obtained through the space forming portion 6.
`
`[9033]
`
`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 deeppeed.
`
`[0034]
`
`In a first method of cutting out
`
`the image of the
`
`capillary 8,
`
`the region of the capillary 8 is specified
`
`beforehand as the coordinates of an image of the image
`
`10
`
`sensor. Since the test piece 10 is positioned and mounted
`
`by the stage 12,
`
`the coordinates on the image sensor
`
`image of the capillary 8 can be set so as to be always
`
`aligned with the stage 12. Thus the image of the region
`
`
`of the capillary & is specified and cut out beforehand
`
`15
`
`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 capiliary 8 is cbtained 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 calied a shorter direction) of the test piece 10
`
`and in the Longitudinal direction (also calied 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,
`
`so
`
`that light is reflected on the porous substrate 2 and the
`
`The space forming portion
`image sensor output increases.
`££
`
`
` fects
`
`6 is made of a transparent resin and thus hardly a
`
`the image sensor output. An air hole 7
`is provided by
` forming a through hole on the space forming portion 6 and
`
`thus light partially reflects on the edge of the air hole
`
`[GO036]
`
`10
`
`Therefore,
`
`the image sensor output on the imaging
`
`extraction line B-B’ has characteristics indicated by the
`
`In FIG. 4, by reading
`lower region of FIG. 4.
` fluctuations in image sensor output between a region {1)
`
`having the air hole 7 and a convex region (2) of the
`
`15
`
`image sensor output appearing on the corresponding end
`
`{the right end (adding deepsetss 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 t#—Re—
`
`peeeties., 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 capiilary 8 is
`
`provided. An image sensor output on the imaging
`
`extraction line C-C’
` FIG. 4.
`
`
`is indicated in the right region of
`
`The image sensor cutput on the imaging extraction
`
`line C-C’ changes at boundaries (3) and {4) between the
`
`capillary 8 and a PET sheet 1.
`
`The specimen of the
`
`capillary 8
`
`in the shorter direction on the test piece 19
`
`is Located ithe—-shertercitrectiorn by reading
`
`fluctuations in image sensor output at the boundaries (3)
`
`In this way,
`
`the specimen in the capillary 8 in_
`
`and (4).
`
`the Longer direction and the shorter direction on the
`
`test piece 10 is located tmhetercesditeccticonasdehe—
`
`shestescitection. During the location of the capillary 8,
`ce
`
`when it is dif!
`icult to determine the points of the
`
`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 capiliary 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
`
`the capillary 8
`
`to the extraction of the image sensor
`
`output at the specific point are repeated until the image
`
`10
`
`sensor output changes. Since the specimen has a Light
`
`absorbing property,
`
`the image sensor output decreases when
`
`the specimen is added deepped to the capillary 8. A time at
`
`which the image sensor output changes is regarded as a
`
`15
`
`specimen adding deepping time. FIG.
`
`5A is an image of a
`
`state of the capillary 8
`
`immediately after the specimen is
`
`the capillary 2 is filied
`added deepped. At this point,
`
`
`
`
`with a specimen X. FIG.
`5B shows a state of the capiilary 8
`
`after a predetermined time since the specimen XK has been
`
`added deesped. The added deesped specimen X develops on the
`
`porous substrate 2 and thus the amount of the specimen X
`
`decreases in the capillar

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