throbber
Description
`
`SOLUTION MEASUREMENT METHOD AND SOLUTION MEASUREMENT
`
`APPARATUS
`
`Technical Field
`
`[0001]
`
`g
`
`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
`to a test piece and is developed thereon and an optical
`
`property 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.
`
`10
`
`15
`
`Background Art
`
`[0002]
`
`As an apparatus for measuring a substance to be
`
`measured in a specimen (also called a solution to be
`
`20
`
`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
`
`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
`
`measurement apparatus will be described below in
`accordance with the exploded perspective view of the test
`
`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
`
`25
`
`30
`
`35
`
`

`

`serves as a development layer for developing the specimen
`
`and a space forming portion 6 that forms a space
`
`(solution storage portion)
`
`for temporarily storing the
`
`specimen,
`
`to a PET sheet 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
`
`measured in the specimen, and an immobilizing portion 4
`
`serves as a portion to 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
`
`prevent drying of the specimen being developed.
`
`[0004]
`
`As shown in FIG. 15,
`
`the porous substrate 2 is bonded
`
`to the PET sheet 1 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 dropped specimen and an air hole
`
`7 that is formed on a part of the space forming portion 6.
`
`By dropping (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 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 immobilizing
`
`10
`
`15
`
`20
`
`25
`
`30
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`35
`
`

`

`
`
`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]
`
`Referring to FIG. 16,
`
`the solution measurement
`
`apparatus of the prior art will be described below. A
`
`solution measurement apparatus 109 is roughly 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
`
`rotating the feed screw 114. The optical section is made
`
`up of a laser diode 116, a condenser lens 117, an opening
`
`118, a beam splitter 119, 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 havfing 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
`
`10
`
`15
`
`20
`
`piece 10. The other beam is incident on the front monitor
`120 made up of a light receiving device such as a photo
`
`25
`
`diode and the front monitor 120 outputs a current
`
`according to the intensity of light. The output current
`a 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.
`
`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
`
`3O
`
`35
`
`

`

`control value.
`
`A current controller 137 passes a current
`
`to the laser diode 116 according to an output 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
`
`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.
`
`10
`
`[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 dropped to the
`
`test piece 10 set on the attachment 110. After the
`
`specimen is dropped,
`
`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 controller 130.
`
`In response to the detection signal,
`
`the motor controller
`
`130 transmits a driving signal 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 piece 10. At the completion of the
`
`movement of the stage 112,
`
`the laser diode 116 is driven
`
`‘ to emit light 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 point. As shown in FIG. 17, 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
`
`15
`
`20
`
`25
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`30
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`35
`
`

`

`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.
`
`[0007]
`
`10
`
`15
`
`20
`
`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 the portion to 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 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 arithmetic unit 136, so that an
`
`absorbance signal of the test piece 10 is obtained. At
`
`the completion of scanning 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.
`
`.25
`
`[0008]
`
`f
`
`In this case, when the amount of the dropped specimen
`
`is insufficient or in the event of an abnormal flow
`
`causing the specimen to clog in the test piece 10,
`
`the
`
`specimen does not flow to the end of the porous substrate
`2, so that the specimen does not reach the light
`
`30
`
`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.
`
`,
`
`Disclosure of the Invention .
`
`Problems to be Solved by the Invention
`[0009]
`'
`‘
`
`In the configuration of the solution measurement
`apparatus of the prior art, however, when there is a time
`
`lag between the dr0pping 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 the specimen cannot be detected}
`
`[0010]
`
`Further, since the viscosities of specimens are not
`
`uniform,
`
`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
`
`10
`
`15
`
`developed, whereas a specimen having a high viscosity is
`
`‘20
`
`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
`
`25
`
`and reduce measurement accuracy.’
`
`[0011]
`
`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
`
`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.
`
`30
`
`35
`
`

`

`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
`
`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,
`
`the development layer having a
`
`id
`
`portion to 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 portion to be
`
`measured,
`
`the method including: measuring the portion to
`
`be measured,
`in response to a reduction of the solution
`to be tested to a predetermined amount or less in the
`
`15
`
`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]
`
`20
`
`25
`
`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 portion to
`
`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.
`
`[0014]
`
`The solution measurement method of the present
`
`invention further includes: measuring a flowing time from
`
`30
`
`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
`
`35
`
`

`

`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 portion to be measured.
`
`[0015]
`
`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
`when added to the test piece,
`the solution to be tested
`
`10
`
`is developed on the development
`
`layer of the test piece
`
`from the solution storage portion,
`
`the development layer
`
`having a portion to be measured, and the amount of a
`
`substance to be measured in the solution to be tested is
`
`15
`
`calculated by measuring the optical property of the
`portion to be measured,
`the method including: measuring
`
`the initial storage amount of the solution to be tested
`
`in the solution storage portion of the test piece, when
`
`the solution to be tested is added to the test piece
`
`20
`
`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 tested is added;
`
`measuring the optical property of the portion to be
`
`25
`
`measured,
`
`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.
`
`30
`
`[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
`
`portion to be measured on the development layer, and
`
`35
`
`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.
`
`[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
`
`. 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
`
`10
`
`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 portion to be measured.
`
`15
`
`[0018]
`
`20
`
`25
`
`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
`
`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
`
`initial storage setting.
`
`[0019]
`
`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 possible to prevent measurement
`
`in an
`
`abnormal state with an insufficient initial storage
`
`

`

`7 10 -
`
`amount,
`
`thereby preventing erroneous measurement of the
`
`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]
`
`10
`
`15
`
`20
`
`25
`
`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 a
`
`predetermined portion to be measured on the development
`
`layer of the test piece,
`
`the solution measurement
`
`apparatus including: an imaging device for imaging the
`portion to 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 tested in the solution storage
`
`portion; and a controller for measuring the portion to be
`
`measured,
`
`in response to a reduction of the solutibn 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 predetermined amount or more in the
`
`solution storage portion, and calculating, based on the,
`
`measured value,
`
`the amount of the substance to be
`
`3O
`
`measured in the solution to be tested.
`
`[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
`
`35
`
`portion to the portion to 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]
`
`The solution measurement apparatus of the present
`
`invention further includes an illuminator for
`
`illuminating the test piece with measurement light; and a
`
`light receiver for receiving the reflected light of the
`
`10
`
`measurement light having illuminated the test piece.
`
`[0024]
`
`.
`
`According to the solution measurement apparatus of
`
`the present invention,
`
`the illuminator is one of an LED,
`
`an LD, and a lamp.
`
`15
`
`[0025]
`
`According to the solution measurement apparatus of
`
`the present invention,
`sensor.
`
`the light receiver is an image
`
`[0026]
`
`20
`
`According to the solution measurement apparatus of
`
`the present invention,
`
`the test piece is a test piece for
`
`chromatography.
`
`Advantage of the Invention
`
`25
`
`[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 a
`
`portion to be measured,
`
`in a state in which a uniform
`
`3O
`
`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
`
`35
`
`[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 dropping according to the first embodiment of the
`
`present invention;
`
`FIG.
`
`4 shows a capillary image obtained by the image
`
`sensor before dropping, and an image sensor output
`
`according to the first embodiment of the present
`
`invention;
`5A shows a capillary image obtained immediately
`FIG.
`after dropping according to the-first embodiment of the
`
`present invention;
`
`FIG. 5B shows a capillary image obtained after a
`
`predetermined time since dropping 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 dropping 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 dropped, 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
`
`10
`
`15
`
`20
`
`25
`
`30
`
`invention;
`
`FIG.
`
`9 shows an optical property measuring process
`
`according to the second embodiment of the present
`
`invention;
`
`

`

`-13..
`
`FIG. 10 shows an image sensor output at a monitor
`
`point according to the second embodiment of the present
`
`invention;
`
`FIG. 11 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 dropping according to the fourth
`embodiment of the present invention;
`4
`
`FIG. 14 is an exploded perspective view showing a
`
`test piece of a solution measurement apparatus according
`
`to the prior art;
`
`V
`
`FIG. 15 is an assembly perspective view showing the
`
`test piece of the solution measurement apparatus
`
`according to the prior art;
`
`FIG. 16 is a schematic diagram showing the solution
`
`measurement apparatus according to the prior art; and
`
`FIG. 17 shows a signal monitor output of the solution
`
`measurement apparatus according to the prior art.
`
`Best Mode for Carrying Out
`
`the Invention
`
`[0029]
`
`A solution measurement apparatus and a solution
`
`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
`
`10
`
`15
`
`20
`
`25
`
`30
`
`measurement method according to the embodiments of the
`
`present invention is configured as in the solution
`
`measurement apparatus of the prior art. Constituent
`
`elements having the same functions will be indicated by
`
`the same reference numerals.
`
`35
`
`(First Embodiment)
`
`

`

`FIG.
`
`1 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
`
`5
`
`10
`
`15
`
`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 (dropped) 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 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
`
`diaphragm 23 for adjusting reflected light from the test
`piece 10, a condenser lens 24 for forming an image of the
`
`20
`
`test piece 10 on the image sensor 22, an image sensor
`
`controller 26, an image processor 30, and a controller
`
`(not shown).
`
`[0030]
`
`25
`
`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.
`
`30
`
`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
`
`35
`
`test piece 10 into the stage 12, and the light source 21
`
`

`

`_ 15 _
`
`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]
`
`'
`
`the following
`Referring to the flowchart of FIG. 2,
`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
`
`solution to be tested has been dropped (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 an immobilizing portion 4 serving as a
`
`portion to be measured 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 dropped. When the detection switch 15.
`
`detects that the test piece 10 has been set,
`
`the
`
`10
`
`15
`
`20
`
`25
`
`3O
`
`measurement start signal is outputted from the error AMP
`
`32 to turn on the light source 21 and the image sensor
`controller 26 is driven to image the test piece 10. This
`
`35
`
`

`

`- 15 _
`
`imaging operation obtains an image shown in FIG. 3.
`
`By
`
`using this image,
`
`the dropping of the specimen on the
`
`test piece 10 is detected.
`
`In order to detect the
`
`dropping of the specimen, an image at the point of the
`
`capillary 8 is recognized in the image of FIG. 3.
`
`A space
`
`forming 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.
`
`10
`
`[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 dropped.
`
`[0034]
`In a first method of cutting out
`
`15
`
`the image of the
`
`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
`
`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 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
`
`20
`
`25
`
`30
`
`method and can sufficiently contain the capillary 8. FIG.
`
`4 shows an image cut out by the second method.
`
`In this
`
`case,'the region of the space forming portion 6 is cut
`
`out as an image. First, an imaging extraction line B—B’
`
`3S
`
`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
`
`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
`
`image sensor output increases. The space forming portion
`
`6 is made of a transparent resin and thus hardly 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]
`
`Thereforer the image sensor output on the imaging
`
`extraction line B-B’ has characteristics indicated by the'
`
`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) appearing
`on the end (the right end (dropping side) of FIG. 4) of
`
`the test piece 10,
`
`the capillary 8 on the test piece 10
`
`10
`
`15
`
`20
`
`in the shorter
`is located in the longer direction. Next,
`direction of the test piece 10, an imaging extraction
`
`25
`
`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 the
`
`imaging extraction line C—C' changes at boundaries (3)
`
`and (4) between the capillary 8 and a PET sheet 1. The
`
`capillary 8 on the test piece 10 is located in the
`
`shorter direction by reading fluctuations in image sensor
`
`output at the boundaries (3) and (4).
`
`In this way,
`
`the
`
`capillary 8 on the test piece 10 is located in the longer
`
`30
`
`35
`
`

`

`-18-
`
`direction and the shorter direction. During the location
`
`of the capillary 8, when it is difficult to determine the
`
`points of the 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]
`
`10
`
`15
`
`20
`
`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 sensor output changes. Since the specimen
`
`has a light absorbing property,
`
`the image sensor output
`
`decreases when the specimen is dropped to the capillary 8.
`
`A time at which the image sensor output changes is
`
`regarded as a specimen dropping time.
`
`FIG.
`
`5A is an image
`
`of a state of the capillary 8 immediately after the
`
`specimen is dropped. At this point,
`
`the capillary 8 is
`
`filled with a specimen X.
`
`FIG. SB shows a state of the
`
`capillary 8 after a predetermined time since the specimen
`
`X has been dropped. The dropped specimen x develops on
`
`the porous substrate 2 and thus the amount of the
`
`25
`
`specimen X decreases in the 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 decreases on the dropping
`
`side is called a dropping-side specimen decreasing region
`
`2.
`
`FIG.
`
`6 shows the experimental measured values of the
`
`amount of the specimen in the capillary 8 relative to an
`
`elapsed time after dropping.
`
`In this experiment, used
`
`blood specimens have a hematocrit
`
`(will be referred to as
`
`Hct) of 20% (indicated by circles) and a hematocrit of
`
`30
`
`35
`
`

`

`40% (indicated by rhombuses) and the amount of the
`
`specimen in the capillary 8 is indicated as an area
`
`recognized on an image.
`
`In this experiment,
`
`the porous
`
`substrate 2 was nitrocellulose and the capillary 8 had
`
`dimensions of, as shown in FIG. 5A, 6.5 mm x 1.7 mm (an
`area of 11.1 mmz)
`in the longer direction and the shorter
`
`direction and a capacity of 5 pl (microliter). As shown
`
`in FIG. 6, a reduction in the amount of the specimen
`
`tends to decrease with the passage of time because the
`
`specimen in the capillary 8 develops on the porous
`substrate 2.
`In this experiment,
`the specimens having a
`
`Hot of 20% and a Hct of 40% both reach the end of the
`
`porous substrate 2 after a lapse of 160 seconds to 220
`
`seconds since the specimen has been dropped. Thus, for
`
`example, when the amount of the specimen in the capillary
`
`8 is 4 mm2 or less or the amount of the specimen has a
`ratio of 0.36 or less relative to the capillary area of
`
`11.1 mmz, it is decided that the flow of the specimen has
`ended.
`
`10
`
`15
`
`20
`
`{0038]
`
`Referring to FIG. 7, a method of determining the
`
`amount of the specimen will be described below.
`
`FIG.
`
`7
`
`shows an image of the capillary 8 and a portion around
`the c

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