throbber
SUBSTITUTE SPECIFICATION — CLEAN
`U_S. Patent Application Serial No. 12/810,391
`Attorney Docket No.: 20249.0050USWO
`
`+3
`
`Description
`
`
`
`
`
`
`SOLUTION MEASUREMENT METHOD AND SOLUTION MEASUREMENT
`
`APPARATUS
`
`
`
`
`
`
`TECHNICAL FIELD
`
`fO001]
`
`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 portion of the test piece
`
`is measured to calculate an amount of substance to be
`
`measured in the solution to be tested.
`
`BACKGROUND ART [0002]
`
`
`
`As an apparatus for measuring a substance to he
`
`measured in a specimen (also called a solution to be
`
`tested} such as blood and plasma, a solution measurement
`
`25
`
`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
`
`being immobilized at a predetermined point, and the
`
`concentration (amount) of the substance to be measured is
`
`30
`
`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
`
`accordance with the exploded perspective
`view of the test
`
`

`

`ho
`
`
`piece in FIG.
`
`14 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
`
`layer for developing the specimen
`
`serves as a development
`
`and a space forming portion 6 that forms a space
`
`(solution storage portion)
`
`specimen,
`
`to a PET sheet
`
`for temporarily storing the
`
`1 serving as the base of the
`
`test piece 10. On the porous substrate 2,
`
`a labeling
`
`portion 3 is provided which is coated with a Labeling
`
`substance to be specifically bound to the substance to be
`
`10
`
`measured in the specimen, and an immobilizing portion 4
`
`on which an antibody to be specifically bound to the
`
`substance to be measured is immobilized. Further,
`
`a PET
`
`film 5 is bonded to prevent drying of the specimen being
`
`15
`
`developed.
`
`[G04]
`
`
`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
`
`temporariiy storing the added specimen and an air hole 7
`
`that is formed on a part of the space forming portion 6.
`
`By 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 immobilizing portion 4,
`
`the
`
`Substance to be measured is immobilized and the remainder
` of the specimen further develops downstream. The labeling
`
`35
`
`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
`
`so that the concentration
`by using a calibration curve,
` of the substance to be measured is determined.
`
`£0005]
`
`Referring to FIG. 16,
`
`the solution measurement
`
`apparatus of the prior art will be described below. 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
`
`setting the test piece 10, a stage 112 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
`
`
`
`10
`
`15
`
`rotating the feed screw 114. The optical section is made
`
`up of a laser diode 116,
`
`118,
`
`a beam splitter 119,
`
`a condenser lens 117, an opening
`
`a front monitor 120,
`
`a
`
`
`
`cylindrical lens 121, and a signal monitor 122. Light
`
`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 i118. The
`
`shaped beam is split by the beam splitter 119. One of the
`
`split beams directly enters the cylindrical lens 171,
`
`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. The output current
` of the front monitor 120 is used for adjusting the light
`
`quantity of the laser diode 116. The output current is
`
`converted to a voltage by an I-V (current-voltage)
`
`converter 131 and then is inputted to an error AMP 132.
`
`35
`
`The error AMP 132 receives an output command value 133 as
`
`

`

`
`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 controller 137 passes a current
`
`to the laser diode 116 according to an cutput
`
`from the
`
`
`
`error AMP 132 to keep constant an optical output.
`In FIG.
`
`16,
`
`reference numeral 130 denotes a motor controller for
`
`controlling the motor 113, reference numeral 122 denotes
`
`
`
`10
`
`15
`
`the signal monitor for detecting reflected Light
`
`test piece 10, and ret
`
`erence numeral 138 denotes an I-V
`
`from the
`
`
`{current-voltage) converter for converting a current
`
`from
`
`the signal monitor 122 to a voltage value.
`
`fO006]
`
`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 to the test
`
`piece 10 set on the attachment 110. After the specimen is
`
`added,
`
`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 signai is
`
`
`
`inputted to the motor controller 130.
`
`In response to the
`
`detection signal,
`
`the motor controller 130 transmits a
`
`driving signai
`
`to the motor 113 to rotate the feed screw
`
`114 and the stage 112 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
`c
`piece 10. At the completion of the movement of the stage
`
`112,
`
`the Laser diode 116 is driven to emit iight to the
`
`test piece 10 and the reflected light is received by the
`
`Signal monitor 122. FIG.
`17
`is a time-series graph
`
`
`
`
`showing the output of the signal monitor 122 at this
`£
`f
`
`point. As shown in FIG.
`17, when the specimen has not
`
`35
`
`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 th
`
`laser irradiation position containing the immobilizing
`
`portion 4,
`
`the output of the signal monitor 122 is
`
`
`reduced by the absorption of light on the specimen. By
`
`detecting a reduction of the monitor output signal
`
`thus,
`
`the arrival of the specimen at the laser irradiation
`
`position is detected.
`
`In the solution measurement
`
`apparatus,
`
`the light of the laser diode 116 is emitted up
`
`to an end of the porous substrate 2,
`
`10
`
`[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
`
`15
`
`started on a solution at the immobilizing portion. The
`
`
`
`motor 113 is driven by the motor controller 130 and the
`
`outgoing light cf the laser diode 116 is scanned on the
`
`test piece 10. A value obtained by performing LOG
`
`conversion on the output
`
`cof
`
`the front monitor 120 by a
`
`LOG converter 134 and a vaiue obtained by performing LOG
`
`conversion on the output of the signal monitor 122 by a
`
`LOG converter 135 are calculated by an arithmetic unit
`
`136,
`
`so that an absorbance signal of the test piece 10 is
`
`the completion of scanning of the test piec
`
`obtained. At
`
`10,
`
`the stage 112 is moved to a position where the
`
`attachment 110 can be removed, and then the measuring
`
`operation is completed.
`
`[0088]
`
`In this case, when the amount of the added specimen
`
`is insufficient or in the event of an abnormal flow
`
`causing the specimen to clog in the test piece 10,
`
`specimen does not flow to the end of the porous substrate
`
`the
`
`2,
`
`so that the specimen does not reach the light
`
`irradiation position of the laser diode 1126.
`
`In this case,
`
`35
`
`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
`
`Problems to be Solved by the Invention
`
`[O00]
`
`10
`
`In the configuration of the solution measurement
`
`apparatus of the prior art, however, when there is a time
`
`lag between the adding of the specimen to the test piece
`
`10 and the setting of the test piece 10 in the solution
`
`measurement apparatus,
`
`the specimen has passed the laser
`
`irradiation position upon detection and thus the flow of
`
`15
`
`the specimen cannot be detected.
`
`fOo16]
`
`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
`
`In other
`
`detected at the laser irradiation position.
`
`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 10, 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
`££
`
`
`
`detect the flow of
`
`a solution to be tested as a specimen
`
`35
`
`and can accurately calculate the amount of a substance to
`
`

`

`~J
`
`
`be measured in a state in which a uniform amount of the
`
`solution to be tested is developed.
`
`Means for Solving the Problems
`
`{QOO12]
`
`
`
`In order to solve the problems of the prior art, a
`
`solution measurement method of the present invention in
`
`which a solution to be tested is temporarily stored in the
`
`solution storage portion of a test piece after the solution
`
`10
`
`is added to the test piece,
`
`transferred from the solution storage portion to the
`
`the solution to be tested is
`
`development Layer and is developed on the development layer
`
`of the test piece,
`the
`development
`
`layer having an
`
`immobilizing portion, and the amount of a substance to be
`
`15
`
`measured in the solution to be tested is calculated by
`
`measuring the optical property of the solution at the
`
`immobilizing portion,
`
`the method including: measuring the
`
`solution at the immobilizing portion,
`
`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.
`
`[G013]
`
`According to this method, it is possibile 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 a
`
` solution to be tested is developed.
`
`state in which substantially a uniform amount of the
`
`[0024]
`
`
`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
`
`35
`
`

`

`
`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.
`
`10
`
`[9025]
`
`A solution measurement method of the present invention
`
`in which a solution to be tested is temporarily stored in
`
`the solution storage portion of a test piece after the
`
`solution is added to the test piece,
`
`tested is transferred from the solution storage portion to
`
`the solution to be
`
`15
`
`the development layer and is developed on the development
`
`layer of the test piece,
`the
`development layer having an
`
`immobilizing 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 the
`
`immobilizing portion,
`
`the method including: measuring the
`
`initial storage amount of the solution to be tested in the
`
`solution storage portion of the test piece, after 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 aiso after
`
`the solution to be tested is added; measuring the optical
`
`property of the solution at the immobilizing portion,
`
`in
`
`response to a reduction of the scaiution to be tested from
`
`the initial storage amount by a predetermined amount
`
`in the
`
`solution storage portion; and caiculating, based on the
`
`measured value,
`
`the amount of the substance to be measured
`
`35
`
`in the solution to be tested.
`
`

`

`fO016]
`
`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
`
`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
`
`tested is developed.
`
`10
`
`fO017]
`
`
`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
`
`15
`
`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.
`
`[G018]
`
`
`The solution measurement method of the present
`
`invention further includes: measuring the initial storage
`
`amount of the solution to be tested in the solution
`co
`
`storage portion of
`
`the test piece, 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; 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
`
`35
`
`initial storage setting.
`
`

`

`FOOL 3]
`
`Thus when the solution to be tested is added to the
`
`test piece mounted in a solution measurement apparatus or
`
`when the test piece on which the solution to be tested
`
`has been added is mounted in the solution measurement
`
`apparatus, it is possibile to prevent measurement
`
`
`
`abnormal state with an insufficient initial storage
`
`thereby preventing erroneous measurement of the
`
`amount,
`
`in an
`
`amount of the substance to be measured.
`
`10
`
`fO020]
`
`Further, according to the solution measurement method
` of the present invention,
`ine
`for chromatography.
`
`the test piece is a test piece
`
`
`
`[0021]
`
`15
`
`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 the development
`
`layer of the test piece,
`
`the solution measurement
`
`apparatus including: an imaging device for imaging the
`
`solution at the predetermined portion and the solution
`co
`
`storage portion of
`
`a solution amount
`
`the test piece;
`
`detector for detecting, based on imaging information,
`
`the
`
`amount of the solution to be tested in the solution
`
`storage portion; and a controller for measuring the
`
`solution at the immobilizing portion,
`
`in response to a
`
`reduction of the solution to be tested to a predetermined
`
`
`
`amount or less in the solution storage portion or a
`
`reduction of the solution to be tested by the
`
`35
`
`predetermined amount or more 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.
`
`[0022]
`
`a
`
`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
`
`10
`
`ccurately 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.
`
`[O023]
`
`The solution measurement apparatus of the present
`
`invention further includes an illuminator for
`
`15
`
`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 Lamp.
`
`£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 present invention,
`
`the test piece is a test piece for
`
`chromatography.
`
`
`
`Advantage of the Invention
`
`[0027]
`
`According to a solution measurement method and a
`
`35
`
`solution measurement apparatus of the present
`
`invention,
`
`

`

`it is possible to measure a substance to be measured in
`
`an immobilizing portion,
`
`in a state 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.
`
`
`
`
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[G028]
`
`10
`
`FIG.
`
`1 schematicaliy 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
`
`15
`
`invention;
`
`FIG.
`
`3 shows an image obtained by an image sensor
`
`before adding of a specimen 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, and an image sensor
`
`output according to the first embodiment of the present
`
`invention;
`
`5A shows a capillary image obtained immediately
`FIG.
` after adding of a specimen according to the first
`
`
`embodiment of the present invention;
`
`FIG.
`
`5B shows a capillary image obtained after a
`
`predetermined time since adding of a specimen 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 of the
`
`specimen according to the first embodiment of the present
`
`invention;
`
`FIG.
`
`7 shows a capillary image obtained by the image
`
`sensor when the specimen is added, 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
`
`5
`
`invention;
`
`FIG.
`
`@ 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
`
`10
`
`point according to the second embodiment of the present
`
`invention;
`
`FIG.
`
`it shows a drop detecting process according toa
`
`third embodiment of the present invention;
`
` FIG. 12 shows a specimen amount detecting process
`
`15
`
`
`according to a fourth embodiment of the present
`
`invention;
`
`FIG. 13 shows a flow rate of a specimen relative to
`co
`
`an elapsed time after adding of a specimen according to
`
`invention;
`the fourth embodiment of the present
`
`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
`
`according to the prior art;
`
`i6 is a schematic diagram showing the solution
`
`FIG.
`
` FIG.
`
`measurement apparatus according to the prior art; and
`
`i7 shows a signal monitor output of the solution
`
`measurement apparatus according to the prior art.
`
`
`
`
`
`
`
`
`
`DETATLED DESCRIPTION OF THE
`INVENTION [0029
`
`beeed
`
`[0029]
`
`
`
`In the present disclosure, a volume of a solution
`
`35
`
`stored in a solution storage portion of a test piece is
`
`

`

`
`measured by an area of the solution multiplying a uniform
`
`thickness of a capillary in the solution storage portion
`
`in a direction perpendicular to a development layer. That
`
`the area of the solution is proportional to the
`
`is,
`
`volume of the solution in the solution storage portion of
`
`the test piece. For convenience of description,
`
`the area
`
`of the solution in the solution storage portion is used
`
`
`to facilitate description of the volume of the solution.
`
`A solution measurement apparatus and a solution
`
`10
`
`measurement method according to embodiments of the
`
`present invention will be specifically described below
`
`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
`
`15
`
`measurement apparatus of the prior art. Constituent
`
`elements having the same functions will be indicated by
`
`
`same
`r
`ference numerals.
`
`the
`
`{First Embodiment)
`
`FIG.
`
`2 schematically shows a solution measurement
`
`apparatus according to an embodiment of the present
`
`invention. First,
`
`the configuration of the solution
`
`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 as a 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 dicde), 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
`
`35
`
`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
`
`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
`
`{net shown).
`
`£0030]
`
`The following will describe the operations of the
`
`In this
`
`light source 21 and the image sensor 22.
`
`10
`
`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
`
`15
`
`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.
`
`{OO031]
` Referring to the flowchart of FIG. 2,
`
`
`the following
`
`will describe the measuring operation processes (solution
`
`measurement method) of the solution measurement apparatus.
`
`A process of measurement is broadly 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
`
`35
`
`solution to be tested has been added 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 optical property of the
`
`solution at an immobilizing portion 4 is measured and is
`
`converted to a concentration (amount) of a substance to
`
`10
`
`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. When the detection switch 15
`
`15
`
`detects that the test piece 10 has been set,
`
`measurement start signal is outputted from the error AMP
`
`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 of the specimen on the test
`
`piece 10 is detected.
`
`the adding of
`Q
`the specimen, an image at the point of the capillary 8 is
`
`recognized in the image of FIG. 3. A space forming
`
`
`In order to detect
`
`portion 6 forming the space of the capillary 8 is made of
`
`a transparent material such as a PET sheet,
`
`so that an
`
`image of the capillary 8 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.
`
`[0034]
`
`In a first method of cutting out
`
`the image of the
`
`the region of the capillary 8 is specified
`
`beforehand as the coordinates of an image of the image
`
`capillary 8,
`
`35
`
`

`

`10
`
`15
`
`sensor. Since the test piece 10 is positioned and mounted
`a
`by the stage 12,
`
`the coordinates on the image sensor
`Q
`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 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
`
`pattern of an output
`
`and the image of the capiliary 8 is obtained from the
`
`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
`
` a
`method and can sufficiently contain the capillary 8. FI
`
`In this
`
`4 shows an image cut out by the second method.
`
`the region of the space forming portion 6 is cut
`
`case,
`
`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 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
`a
`.
`is made of
`sensor output decreases. A porous substrate 2
`
`a white material or a material not absorbing light,
`5
`that light is reflected on the porous substrate 2 and the
`
`so
`
`image sensor output increases. The space forming portion
`
`
`
`
`6 is made of a transparent resin and thus hardiy affects
`
`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
`
`7.
`
`[0036]
`
`

`

`Therefore,
`
`the image sensor output on the imaging
`
`extraction line B-B’ has characteristics indicated by the
`co
`
`
`
`lower region of FIG. 4.
`
`In FIG. 4, by reading
`
`fluctuations in image sensor output between a region (1)
`
`having the air hole 7 and a convex region (2) of the
`
`image sensor output appearing on the corresponding end
`
`{the right end (adding 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. Next,
`
`in the
`
`10
`
`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’
`
`is indicated
`
`
`in the right region of FIG. 4.
`
`The image sensor output on
`
`15
`
`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 §
`
`in the shorter direction
`
`on the test piece 10 is located by reading fluctuations
`
`in image sensor output at the boundaries (3) and (4).
`
`In
`
`this way,
`
`the specimen in the capillary 8
`
`in the longer
`
`direction and the shorter direction on the test piece 10
`
`
`is located. During the location of the capillary 8, when
`
`it is difficult to determine the points of the regions
`
`to (4)
`
`(1)
`
`of the image sensor output
`
`
`shown in FIG. 4,
`
`the brightness and contrast
`
`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
`“ pecific 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
`
`35
`
`sensor output changes. Since the specimen has a Light
`
`

`

`absorbing property,
`
`the image sensor output decreases when
`
`the specimen is added to the capillary 8. A time at which
`
`the image sensor output changes is regarded as a specimen
`
`5A is an image of a state of the
`
`
`adding time. FIG.
`
`5
`
`this point,
`
`capillary 8
`
`immediately after the specimen is added. At
`
`the capillary 8
`is filled with a specimen X.
`
`
`
`FIG. 5B shows a state of the capiilary 8 after a
`
`predetermined time since the specimen X has been added. The
`
`added specimen X develops on the porous substrate 2 and
`co
`
`thus the amount of the specimen X decreases in the
`
`10
`
`capillary 8. At this point,
`
`the specimen X decreases and
`
`the porous substrate 2 is exposed on the side of the air
`
`hole 7. This region is called an air-hole side specimen
`
`decreasing region Y and a region where the specimen X
`
`15
`
`decreases on the adding side is called an adding-side
`
`specimen decreasing region 4. FIG.
`
`6 shows the experimental
`
`measured values of the amount of the specimen in the
`
`capillary 8 relative to an elapsed time after adding the
`
`
`
`specimen.
`
`20
`
`hematocrit
`
`in this experiment,

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