Microchannel analyzing device having a filling confirmation region
09757722 · 2017-09-12
Assignee
Inventors
Cpc classification
B01L2200/06
PERFORMING OPERATIONS; TRANSPORTING
A61B5/150251
HUMAN NECESSITIES
B01L3/502738
PERFORMING OPERATIONS; TRANSPORTING
B01L2400/0688
PERFORMING OPERATIONS; TRANSPORTING
G01N2035/00237
PHYSICS
B01L3/50273
PERFORMING OPERATIONS; TRANSPORTING
A61B5/157
HUMAN NECESSITIES
B01L2300/047
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0636
PERFORMING OPERATIONS; TRANSPORTING
A61B5/150343
HUMAN NECESSITIES
B01L3/5021
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/046
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502
PERFORMING OPERATIONS; TRANSPORTING
A61B5/14532
HUMAN NECESSITIES
A61B5/150755
HUMAN NECESSITIES
Y10T436/111666
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
B01L2300/0816
PERFORMING OPERATIONS; TRANSPORTING
A61B5/1455
HUMAN NECESSITIES
International classification
B01L3/00
PERFORMING OPERATIONS; TRANSPORTING
A61B5/145
HUMAN NECESSITIES
G01N35/00
PHYSICS
A61B5/157
HUMAN NECESSITIES
Abstract
An analyzing device has a main body and is configured to draw a sample liquid from a spot application section of the main body and transfer the sample liquid to a measurement chamber via a microchannel structure formed inside the main body by a centrifugal force. The spot application section has an inlet. The analyzing device includes a supplying capillary channel formed within the spot application section. The supplying capillary channel has an end connected to the inlet of the spot application section. The analyzing device also includes a holding chamber connected to another end of the supplying capillary channel and having a thickness sized to generate a capillary force to move the sample liquid. The holding chamber is formed between a first side wall and a second side wall. The first side wall and the second side wall define the holding chamber.
Claims
1. An analyzing device having a main body, the analyzing device being configured to draw a sample liquid from a spot application section of the main body and transfer the sample liquid to a measurement chamber of the main body via a microchannel structure formed inside the main body by a centrifugal force, the spot application section having an inlet, the analyzing device comprising: a supplying capillary channel formed within the spot application section, the supplying capillary channel having an end connected to the inlet of the spot application section; a holding chamber connected to another end of the supplying capillary channel, the holding chamber having a thickness sized to generate a capillary force to move the sample liquid, the holding chamber being formed between a first side wall and a second side wall; the first side wall and the second side wall defining the holding chamber; and a filling confirmation region formed at a trailing end of the holding chamber, the filling confirmation region being located centrally between the first side wall and the second side wall without contacting either the first side wall or the second side wall, the holding chamber being located between the filling confirmation region and the supplying capillary channel, wherein the filling confirmation region has a thickness that is smaller than a thickness of a recessed portion located between the filling confirmation region and the first side wall, and wherein the holding chamber has a uniform thickness.
2. The analyzing device according to claim 1, wherein a confirmation window is formed on the main body in correspondence to the filling confirmation region.
3. The analyzing device according to claim 1, wherein the main body comprises a cover substrate and a base substrate with an internal recess that makes up the holding chamber defined between the cover substrate and the base substrate, the filling confirmation region is formed between the cover substrate and a protrusion that protrudes from the base substrate toward the cover substrate, and the thickness of the filling confirmation region is formed between an upper end of the protrusion and the cover substrate, the thickness of the filling confirmation region being smaller than the thickness of the holding chamber; the filling confirmation region being sized to allow a capillary force to act on the sample liquid contained in the filling confirmation region.
4. The analyzing device according to claim 1, wherein the main body comprises a cover substrate and a base substrate with an internal recess that makes up the holding chamber defined between the cover substrate and the base substrate, the recess portion is formed at a bottom of the base substrate, and the thickness of the recess portion is measured between the base substrate and the cover substrate, the thickness of the recess portion being greater than the thickness of the holding chamber, the recess portion being sized to allow a capillary force to act on the sample liquid contained in the recess portion.
5. The analyzing device according to claim 1, wherein a second recess having a thickness greater than the thickness of the filling confirmation region is provided between the filling confirmation region and the second side wall.
6. The analyzing device according to claim 5, wherein the main body comprises a cover substrate and a base substrate with an internal recess that makes up the holding chamber defined between the cover substrate and the base substrate, a protrusion protruding from the base substrate toward the cover substrate being formed between the filling confirmation region and the base substrate, the thickness of the filling confirmation region being formed between an upper end of the protrusion and the cover substrate, the thickness of the filling confirmation region being smaller than the thickness of the holding chamber; the filling confirmation region being sized to allow a capillary force to act on the sample liquid contained in the filling confirmation region.
7. The analyzing device according to claim 1, wherein the analyzing device is configured to move the sample liquid from the supplying capillary channel to the holding chamber and to the filling confirmation region by capillary force.
8. The analyzing device according to claim 1, wherein the main body comprises a cover substrate and a base substrate with an internal recess that makes up the holding chamber defined between the cover substrate and the base substrate, a protrusion protruding from the base substrate toward the cover substrate being formed between the filling confirmation region and the base substrate, the thickness of the filling confirmation region being formed between an upper end of the protrusion and the cover substrate, the thickness of the filling confirmation region being smaller than the thickness of the holding chamber; the filling confirmation region being sized to allow a capillary force to act on the sample liquid contained in the filling confirmation region.
9. An analyzing system comprising: the analyzing device of claim 1, and an optical measurement unit that reads the sample liquid by irradiating light to the measurement chamber of the main body of the analyzing device.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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BEST MODE FOR CARRYING OUT THE INVENTION
First Embodiment
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(125) The analyzing device 1 is made up of four parts including: a base substrate 3 with one face on which is formed a microchannel structure having minute irregularities on a surface thereof; a cover substrate 4 for covering a surface of the base substrate 3; a diluent container 5 holding a diluent; and a protective cap 2 for preventing scattering of a sample liquid.
(126) The base substrate 3 and the cover substrate 4 are bonded in a state where the diluent container 5 and the like are internally set, whereby the protective cap 2 is attached to the base substrate 3 and the cover substrate 4 in the bonded state.
(127) By covering the openings of the several depressions formed on the upper face of the base substrate 3 with the cover substrate 4, a plurality of containment areas to be described later (the same as the measurement spots to be described later) and channels having microchannel structures which interconnect the containment areas are formed. Among the containment areas, those required hold, in advance, reagents necessary for performing various analyses. One side of the protective cap 2 is pivotally supported so as to be capable of engaging shafts 6a and 6b formed on the base substrate 3 and the cover substrate 4 and to be openable and closable. When a sample liquid to be tested is blood, gaps between respective channels with microchannel structures in which capillary force acts are set to 50 μm to 300 μm.
(128) An analysis process using the analyzing device 1 described above can be summarized as spot-applying a sample liquid to the analyzing device 1 in which a diluent has been set in advance, and performing measurement after diluting at least a portion of the sample liquid with the diluent.
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(134) When the protective cap 2 is opened as illustrated in
(135) In this case, a sample liquid is spot-applied to an exposed inlet 13 of the analyzing device 1 and the protective cap 2 is closed. At this point, by closing the protective cap 2, a wall face 14 forming the locking groove 12 abuts a face 5b of the latch 10 of the diluent container 5 on a side of the protective cap 2 and pushes the diluent container 5 in the direction of the arrow J (in a direction approaching the liquid discharge position). An opening rib 11a is formed on the diluent container containing section 11 as a protrusion from a side of the base substrate 3. When the diluent container 5 is pushed by the protective cap 2, as illustrated in
(136) A component analysis of a sample liquid can be performed by setting the analyzing device 1 onto a rotor 101 of an analyzing apparatus 100 with the cover substrate 4 facing downwards as illustrated in
(137) A groove 102 is formed on an upper face of the rotor 101. When the analyzing device 1 is set on the rotor 101, a rotation supporting section 15 formed on the cover substrate 4 of the analyzing device 1 and a rotation supporting section 16 formed on the protective cap 2 engages the groove 102 and the analyzing device 1 is contained.
(138) After setting the analyzing device 1 on the rotor 101, when a door 103 of the analyzing apparatus is closed before rotating the rotor 101, a movable piece 104 provided on a side of the door 103 pushes a position of the set analyzing device 1 on the rotation axial center of the rotor 101 towards the rotor 101 using a biasing force of a spring 105, thereby causing the analyzing device 1 to integrally rotate with the rotor 101 that is rotationally driven by a rotation driving unit 106. Reference numeral 107 denotes an axial center during rotation of the rotor 101. The protective cap 2 is attached in order to prevent sample liquid adhering to a vicinity of the inlet 13 from scattering to the outside due to centrifugal force during an analysis.
(139) Resin material with low material cost and superior mass productivity is desirably used for the parts that make up the analyzing device 1. Since the analyzing apparatus 100 analyzes sample liquids using an optical measurement method in which light transmitted through the analyzing device 1 is measured, a synthetic resin with a high optical transparency such as PC, PMMA, AS, MS, and the like is desirably used as the material for the base substrate 3 and the cover substrate 4.
(140) In addition, since it is required that the diluent 8 be sealed inside the diluent container 5 over a long period of time, a crystalline synthetic resin with a low moisture permeability such as PP and PE is desirably used as the material of the diluent container 5. As for the material of the protective cap 2, any material with good moldability shall suffice. Inexpensive resins such as PP and PE are desirable.
(141) The bonding between the base substrate 3 and the cover substrate 4 is desirably performed using a method that is unlikely to affect the reaction activity of reagents held in the containment areas. Desirable methods include ultrasonic welding and laser welding which are less likely to create reactive gases or solvents during bonding.
(142) In addition, a portion for transferring a solution by a capillary force of a minute gap between the base substrate 3 and the cover substrate 4 formed by the bonding of the two substrates 3 and 4 is subjected to a hydrophilic treatment to enhance capillary force. Specifically, a hydrophilic treatment using a hydrophilic polymer or a surfactant is performed. In this case, hydrophilicity refers to a contact angle of less than 90 degrees with respect to water, and more favorably, a contact angle of less than 40 degrees.
(143)
(144) The analyzing apparatus 100 is made up of: a rotation driving unit 106 for rotating the rotor 101; an optical measurement unit 108 for optically measuring a solution in the analyzing device 1; a control unit 109 that controls the rotational speed and rotational direction of the rotor 101, the measurement timing of the optical measurement unit, and the like; a computing section 110 for processing a signal obtained by the optical measurement unit 108 and computing a measurement result; and a displaying section 111 for displaying a result obtained by the computing section 110.
(145) In addition to rotating the analyzing device 1 around the rotation axial center 107 via the rotor 101 in any direction at a predetermined rotational speed, the rotation driving unit 106 is arranged so as to be capable of causing the analyzing device 1 to perform a left-right reciprocating movement centered around the rotation axial center 107 at a predetermined stop position and at predetermined amplitude range and frequency so as to swing the analyzing device 1.
(146) The optical measurement unit 108 includes: a light source 112 for irradiating light to a measurement section of the analyzing device 1; and a photodetector 113 that detects a light intensity of transmitted light having passed through the analyzing device 1 among the light irradiated from the light source 112.
(147) The analyzing apparatus 100 is arranged such that, by rotationally driving the analyzing device 1 by the rotor 101, a sample liquid or a solution taken inside from the inlet 13 is transferred inside the analyzing device 1 by a centrifugal force that is generated by rotating the analyzing device 1 around the rotation axial center 107 positioned circumferentially inward from the inlet 13 and by a capillary force of a capillary channel provided inside the analyzing device 1. A microchannel structure of the analyzing device 1, together with analysis processes, will now be described in detail.
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(150) Instead of being a rectangular shape whose back end-side is vertical as illustrated in
(151) A separation cavity 23 as a receiving cavity with a gap at which capillary force does not act is formed via and beyond the capillary cavity 19 as seen from the guide section 17. A cavity 24 whose one end is connected to the separation cavity 23 and the other end opened to the air is formed to a side of the capillary cavity 19 and parts of the bent section 22 and the guide section 17. Due to the action of the cavity 24, as illustrated in
(152)
Process 1
(153) The analyzing device 1 is set on the rotor 101 in a state where, as illustrated in
Process 2
(154) When the rotor 101 is rotationally driven clockwise (direction depicted by C2) after closing the door 103, the held sample liquid is broken at the position of the bent section 22. A sample liquid inside the guide section 17 is discharged into the protective cap 2. The sample liquid 18 inside the capillary cavity 19 flows into the separation cavity 23 and is centrifugally separated in the separation cavity 23 into a blood plasma component 18a and a blood cell component 18b as illustrated in
(155) With respect to the diluent container 5, the shape of a bottom on the opposite side to the opening 7 sealed by the aluminum seal 9 is formed by an arc face 32 as illustrated in
Process 3
(156) Next, when the rotation of the rotor 101 is stopped, the blood plasma component 18a is siphoned by a capillary cavity 33 formed on a wall face of the separation cavity 23 and then flows into a measurement channel 38 via a capillary channel 37 that communicates with the capillary cavity 33 as illustrated in
Process 4
(157) When the rotor 101 is rotationally driven counter-clockwise (direction depicted by C1), as illustrated in
Process 5
(158) The rotor 101 is rotated counter-clockwise (direction depicted by C1) or clockwise (direction depicted by C2). A reference value is determined when the computing section 110 reads a detected value of the photodetector 113 at a timing where a measurement spot of the reference measurement chamber 31 passes between the light source 112 and the photodetector 113. Furthermore, the computing section 110 reads a detected value of the photodetector 113 at a timing where a measurement spot of the measurement chamber 40 passes between the light source 112 and the photodetector 113 to calculate a specific component based on the reference value.
(159) As seen, since a user can open the diluent container 5 and transfer a diluted liquid into the analyzing device 1 by an opening/closing operation of the protective cap 2 when collecting a sample liquid, an analyzing apparatus can be simplified, cost can be reduced, and user operability can be improved.
(160) Furthermore, since the diluent container 5 sealed by the aluminum seal 9 as a seal member is used and the diluent container 5 is opened by breaking the aluminum seal 9 with the opening rib 11a as a protrusion, a diluent does not evaporate and decrease even during long-term preservation, thereby enabling improvement in analytical precision to be realized.
(161) Moreover, in a shipping state of the analyzing device 1 illustrated in
(162)
(163) Shapes from the inlet 13 to a vicinity of the capillary cavity 19 will be described in detail.
(164) As illustrated in
(165) Furthermore, for the purpose of improving safety, as illustrated in
(166) Moreover, as illustrated in
(167) In addition, since the analyzing apparatus 100 rotationally drives the analyzing device 1 around the rotation axial center 107 (the center of the groove 42 provided on a lower face of the diluent container 5) set inside the analyzing device 1, a turning radius can be reduced in comparison to a conventional analyzing apparatus that rotationally drives the analyzing device 1 around an axial center set to the outside of the analyzing device 1, thereby enabling downsizing to be achieved.
(168) In each embodiment presented above, a case where the groove 42 is provided on a lower face of the diluent container 5 has been described as an example. Alternatively, the groove 42 may be provided on an upper face of the diluent container 5, and the hole 43 may be provided on the base substrate 3 so as to correspond to the groove 42, whereby the protrusion 44a of the locking jig 44 is to be brought into engagement with the groove 42.
(169) In the embodiment described above, the locking groove 12 of the protective cap 2 directly engages the latch 10 of the diluent container 5 to lock the diluent container 5 at the liquid holding position. Alternatively, the diluent container 5 may be locked at the liquid holding position by having the locking groove 12 of the protective cap 2 and the latch 10 of the diluent container 5 indirectly engage each other.
(170) In each embodiment presented above, a case has been described as an example in which a component centrifugally separated from a sample liquid by rotating the analyzing device 1 around the rotation axial center 107 and the diluent 8 discharged from the diluent container 5 are transferred to the measurement chamber 40 to be diluted, whereby analysis is performed by accessing a solution component separated from a sample liquid or a reactant of a solution component separated from a sample liquid and a reagent. However, when a solution component need not be separated from a sample liquid, the separation process is no longer required. In this case, the analyzing device 1 is rotated around the rotation axial center 107 to transfer all of a fixed amount of a sample liquid among a spot-applied sample liquid and the diluent 8 discharged from the diluent container 5 to the measurement chamber 40 to be diluted, whereby analysis is performed by accessing a solution component diluted by the diluent or a reactant of a solution component diluted by the diluent and a reagent. Alternatively, the analyzing device 1 may be rotated around the rotation axial center 107 to transfer a solid component separated from a sample liquid and a diluent discharged from the diluent container 5 to the measurement chamber to be diluted, whereby analysis may be performed by accessing the solid component separated from the sample liquid or a reactant of the solid component separated from the sample liquid and a reagent.
(171) In the embodiment described above, an analyzing device main body having, formed inside, a microchannel structure with minute surface irregularities is structured with two layers, namely, the base substrate 3 and the cover substrate 4. Alternatively, the analyzing device main body may be structured by pasting together three or more substrates. Conceivable specific examples include a three-layer structure that is a microchannel structure formed by setting a substrate notched according to a microchannel structure at center, pasting separate substrates on an upper face and a lower face of the central substrate, and closing the notches.
Second Embodiment
(172)
(173) With the structure of the analyzing device 1 according to the first embodiment, as illustrated in
(174) In consideration thereof, in the present second embodiment, a part of an inner face of a base substrate 3 forming a portion of an inlet 13 of the base substrate 3 and a cover substrate 4 as illustrated in
(175) In the case of the structure of the analyzing device 1 in which a liquid reservoir 122 is formed, by setting the analyzing device 1 to a vertical posture or by inclining the posture of the analyzing device 1 as illustrated in
(176) Due to such a configuration, even when the analyzing device 1 is detached from the fingertip after the inlet 13 is brought into contact with the blood drop 121, as illustrated in
Third Embodiment
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(178) With the analyzing device 1 according to the second embodiment described above, a portion of the inner face of the base substrate 3 is thinly molded so as to form the liquid reservoir 122. However, with the analyzing device 1B according to the present third embodiment, by reducing a length of a cover substrate 4 forming a portion of an inlet 13 of a base substrate 3 and the cover substrate 4 as illustrated in
(179) In the case of the structure of the analyzing device 1B in which a liquid reservoir 122 is formed, by inclining the posture of the analyzing device 1 as illustrated in
(180) Due to such a configuration, even when the analyzing device 1 is detached from the fingertip after the inlet 13 is brought into contact with the blood drop 121, blood as a sample adhered to the liquid reservoir 122 is suctioned up to a capillary cavity 19 by the capillary forces of the guide section 17 and the capillary cavity 19. In addition, after detaching the analyzing device 1 from the fingertip, by maintaining the analyzing device 1 at a posture such as a horizontal posture in which gravity is less likely to affect suction of a sample liquid, blood suction time can be reduced. Furthermore, since a fixed amount of blood can be sampled even when a period of time in which the analyzing device 1 is brought into contact with the fingertip 120 of the testee is shorter than what is conventional, accurate analysis can be realized.
Fourth Embodiment
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(182) With the analyzing device 1B according to the third embodiment described above, the liquid reservoir 122 formed in an arc-like shape on the leading end 4a of the cover substrate 4 is formed as an arc-like shape perpendicular to the base substrate 3. However, with the analyzing device 1C according to the present fourth embodiment, as illustrated in
(183) In the case of the structure of the analyzing device 1C in which a liquid reservoir 122 is formed, by inclining the posture of the analyzing device 1 as illustrated in
(184) Due to such a configuration, even when the analyzing device 1 is detached from the fingertip after the inlet 13 is brought into contact with the blood drop 121, blood as a sample adhered to the liquid reservoir 122 is suctioned up to a capillary cavity 19 by the capillary forces of the guide section 17 and the capillary cavity 19. In addition, after detaching the analyzing device 1 from the fingertip, by maintaining the analyzing device 1 at a posture such as a horizontal posture in which gravity is less likely to affect suction of a sample liquid, blood suction time can be reduced. Furthermore, by forming the groove 123, even when blood is not spherically formed on the fingertip (a state where blood wets and spreads across the fingertip), blood can be guided to the guide section 17 via the groove 123. While only one groove 123 has been formed in the present embodiment, a plurality of grooves may be formed. Moreover, the cross-sectional shape of the groove 123 may be formed so as to have an arc-like shape, a triangular shape, or a quadrangular shape.
Fifth Embodiment
(185) For the respective embodiments described above, the case of an analyzing device that transfers a sample liquid suctioned via a guide section 17 and a capillary cavity 19 to a subsequent-stage measurement chamber 40 and which is to be used for reading involving accessing a test object in the measurement chamber 40 as a measurement spot has been described as an example. However, even in a case of an analyzing device that directly suctions a sample liquid from an inlet 13 to a measurement chamber having a capillary force and which is to be used for reading involving accessing a test object in the measurement chamber, by providing the liquid reservoir 122 described in the second to fourth embodiments, blood adhering to the liquid reservoir 122 can be suctioned by a capillary force of a measurement chamber even when the inlet 13 is only brought into contact with a blood drop for a short period of time. Consequently, the fixed amount of blood can be sampled and accurate analysis can be realized.
(186) In addition, a filter member can be provided on a part of or all of the liquid reservoir 122 according to the respective embodiments described above, whereby a component to be suctioned from the liquid reservoir 122 into the guide section 17 having a capillary force or into a measurement chamber having a capillary force can be selected by the filter member. Specifically, when the sample liquid is blood, by preventing or reducing the passage of a blood cell component by the filter member, a component to come into contact with a reagent inside the measurement chamber can be selected, thereby enabling a precise reaction between the reagent and a blood plasma component and a reduction in variances in the reaction. Consequently, an improvement in analytical precision can be expected.
Sixth Embodiment
(187) The gap between the base substrate 3 and the cover substrate 4 at the portion of the capillary cavity 19 illustrated in
(188)
(189) The analyzing device 1D is made up of a base substrate 3 having a thickness of 0.1 mm to 7 mm and on which a recess is formed, and a cover substrate 4 having a thickness of 1 mm to 7 mm to be bonded to the base substrate 3. For example, both the base substrate 3 and the cover substrate 4 are made from a transparent base material.
(190) A microchannel 203 is formed between the base substrate 3 and the cover substrate 4 bonded together with an adhesive. The microchannel 203 includes: a sample measuring section 201 made up of a capillary channel and which quantitatively measures a fixed amount of a sample liquid to be analyzed; and a receiving section 202 connected to the sample measuring section 201 and which accepts the fixed amount of the sample liquid measured by the sample measuring section 201 and causes a reaction with a reagent. Specifically, a reagent is contained in the receiving section 202 so that a reaction immediately occurs once the sample liquid is transferred to the receiving section 202. The reagent may either be a solid reagent or a reagent applied to a wall face. For example, glucose oxidase or glucose dehydrogenase for glucose measurement, cholesterol esterase or cholesterol hydrogenase for cholesterol measurement, and the like may be used as the reagent.
(191) The inlet 206a is formed on a sample collecting section 206 on one end of the sample measuring section 201. Another end of the sample measuring section 201 is connected to the receiving section 202. The sample collecting section 206 is formed so as to have an arc-like shape with a width Wc as its diameter.
(192) Although an external shape of the analyzing device 1D differs from the external shapes of the analyzing devices 1, 1A, 1B, and 1C according to the respective embodiments described above, in the present embodiment, the shape of a boundary between the sample measuring section 201 and the receiving section 202 has been creatively designed in order to prevent more than a required amount of a sample liquid from entering the receiving section 202 from the sample measuring section 201. The sample collecting section 206 corresponds to the inlet 13 according to the respective embodiments described above. The sample measuring section 201 corresponds to the capillary cavity 19, and the receiving section 202 to the separation cavity 23.
(193) The sample measuring section 201 is made up of: a capillary channel primary segment 207a with a gap that is uniform in a direction towards the receiving section 202 from the sample collecting section 206 (direction depicted by arrow F); and a connected section 207b between the receiving section 202 and a trailing end position P1 of the primary segment 207a.
(194) More specifically, in a capillary channel whose gap dimension is the same as the primary segment 207a at the connected section 207b of the sample measuring section 201, partition walls 401a and 401b that split the channel in a width direction are formed at an interval in the width direction of the channel.
(195) The partition walls 401a and 401b are formed in a slope that rises towards the receiving section 202. The heights of the partition walls 401a and 401b at a connected plane of the sample measuring section 201 and the receiving section 202 are equal to the gap of the capillary channel of the sample measuring section 201.
(196) In
(197) A part of or all of wall faces of the base substrate 3 and the cover substrate 4 have been subjected to hydrophilic treatment in order to reduce viscous resistance within the microchannel 203 and promote fluid movement. Specifically, any of a bottom (the side of the base substrate 3) or a ceiling (the side of the cover substrate 4) of the sample measuring section 201 and the receiving section 202 is formed by a continuous plane subjected to hydrophilic treatment. The partition walls 401a and 401b have also been subjected to hydrophilic treatment.
(198) In this case, hydrophilicity refers to a contact angle of less than 90 degrees with respect to water, and more favorably, a contact angle of less than 40 degrees. Specifically, methods of such hydrophilic treatment include a surface treatment method using plasma, corona, ozone, or an active gas such as fluorine, and surface treatment with a surfactant.
(199) Alternatively, a hydrophilic material such as glass may be used for at least one of the base substrate 3 and the cover substrate 4, or a hydrophilizing agent such as a surfactant, a hydrophilic polymer, and a hydrophilic powder such as a silica gel may be added when molding at least one of the base substrate 3 and the cover substrate 4 so as to impart a material surface with hydrophilicity.
(200) A process in which a sample liquid is collected in the analyzing device 1D created as described above and a fixed amount is measured is illustrated in
(201) In
(202) Next, as illustrated in
(203) This occurs because a part of a wall face that has been continuous in a flowing direction of the sample liquid is severed by a face of the coupled section of the sample measuring section 201 and the receiving section 202, resulting in a decrease in a wet interfacial tension due to the sample liquid flowing in a direction of the receiving section 202 and breaking the capillary force that had been previously dominant.
(204) Moreover, by providing two partition walls 401a and 401b formed from a face where the sample measuring section 201 and the receiving section 202 are coupled towards the inside of the sample measuring section 201, an interface of the sample liquid filling the sample measuring section 201 becomes continuous at the coupled section of the sample measuring section 201 and the receiving section 202. In addition, by reducing a rate of contact with wall faces subjected to hydrophilic treatment, a surface tension of the sample liquid can be arranged so as to exceed a wet interfacial tension from the sample measuring section 201 towards the receiving section 202. As a result, an overflow amount of the sample liquid into the receiving section 202 can be suppressed.
(205) An effect of the present sixth embodiment will now be described based on specific dimensions.
(206) When causing a reaction between a sample liquid and a reagent disposed in the receiving section 202 to measure absorbance, 10 μL of the sample liquid must be collected at the sample measuring section 201. In addition, for the purpose of improving analytical precision, it is required that quantitative variance at the sample measuring section 201 be kept to within ±5% or, in other words, 9.5 to 10.5 μL of the sample liquid must be collected. In consideration thereof, the shape of the sample measuring section 201 is set such that: length Lc=5.0 mm; width Wc=5.0 mm; and thickness Dc=0.3 mm. In addition, the partition walls 401a and 401b are given a sloped shape whose width W1=0.6 mm and length L1=1 mm and are designed to split a portion between the coupled section of the sample measuring section 201 and the receiving section 202 and a position 1 mm towards the inside of the sample measuring section 201 into three equal parts.
(207) A relationship in this case between the width W1 of the partition walls 401a and 401b of the coupled section of the sample measuring section 201 and the receiving section 202 and an overflow amount of a sample liquid that overflows into the receiving section 202 is illustrated in
(208) It is shown that when the width W1 of the partition walls 401a and 401b is set such that W1=0.6 mm, the overflow amount is 0.32 μL. It is also shown that the overflow amount to the receiving section 202 can be suppressed by increasing the width W1 of the partition walls 401a and 401b. In a case where the partition walls 401a and 401b do not exist (W1=0), the overflow amount of the sample liquid to the receiving section 202 is 0.68 W4.
(209) These results indicate that by disposing the partition walls 401a and 401b at the coupled section of the sample measuring section 201 and the receiving section 202, control reliability of a sample liquid at the coupled section of the sample measuring section 201 and the receiving section 202 can be improved and the sample liquid can be accurately measured. Collection of blood measured by the sample measuring section 201 is completed in this state to enable a sample liquid to be analyzed with high accuracy.
(210) In the embodiment described above, while two partition walls 401a and 401b have been formed in a capillary channel of the connected section 207b of the sample measuring section 201 and the receiving section 202, even when the number of partition walls splitting the channel in a width direction is one or three or more, a reduction in the overflow amount of a sample liquid to the receiving section 202 has been confirmed in comparison to a case where no partition walls are provided (W1=0).
Seventh Embodiment
(211)
(212) The analyzing apparatus is configured as illustrated in
(213) A recess 116 on which is set the analyzing device 1D having collected a sample liquid is formed on a disk-like rotor 101A to be rotationally driven around a rotation axial center 107 by a rotation driving unit 106 that is a motor or the like. A penetrating hole 114 is provided in the recess 116 in correspondence to a position of a receiving section 202 of the set analyzing device 1D.
(214) An optical measurement unit 108 that accesses the receiving section 202 of the analyzing device 1D set on the rotor 101A is made up of a light source 112 and a photodetector 113 disposed with the rotor 101A in-between so as to be able to receive light that passes through the hole 114 of the rotor 101A.
(215) A control unit 109 controls a rotational speed and a rotational direction of the rotor 101A, a measurement timing of the optical measurement unit 108, and the like. More specifically, in addition to controlling the rotation driving unit 106 so as to rotate the analyzing device 1D around the rotation axial center 107 via the rotor 101A in any direction at a predetermined rotational speed, the control unit 109 is arranged so as to be capable of causing the analyzing device 1D to perform a left-right reciprocating movement centered around the rotation axial center 107 at a predetermined stop position and at a predetermined amplitude range and a predetermined frequency so as to swing the analyzing device 1D.
(216) A detection light 115 outputted from the light source 112 is transmitted through the hole 114 of the rotor 101A and through a reactant in the receiving section 202 of the set analyzing device 1D, and is received by the photodetector 113 and inputted to a computing section 110. The computing section 110 analyzes characteristics of the sample liquid from an absorption measurement result and displays the characteristics on a displaying section 111.
(217) A centrifugal transfer process and a reagent reaction process of the sample liquid measured by a sample measuring section 201 will be described with reference to
(218) After setting and fixing the analyzing device 1D whose sample measuring section 201 has been filled with a sample liquid onto the recess 116 of the rotor 101A, by rotating the rotor 101A in a direction depicted by an arrow as illustrated in
(219) The rotor 101A is swingingly moved so as to accelerate a reaction with a reagent. The swinging operation is performed by repetitively changing rotational directions of the rotor 101A. Specifically, by swingingly moving clockwise and counter-clockwise respectively over ±1 degrees in a state where the microchannel 203 of the analyzing device 1D is oriented in a nine o'clock direction as illustrated in
(220) The analyzing apparatus 100 processes a result of an absorbance measurement by the optical measurement unit 108 with the computing section 110 and displays an analysis result of characteristics of the sample liquid on the displaying section 111.
(221) As shown, since the control unit 109 instructs the rotation driving unit 106 to swingingly move the analyzing device 1D via the rotor 101A, the sample liquid can be analyzed with extremely high accuracy.
(222)
Eighth Embodiment
(223) The gap between the base substrate 3 and the cover substrate 4 at the portion of the capillary cavity 19 illustrated in
(224)
(225) The analyzing device 1E is made up of a base substrate 3 having a thickness of 1 mm to 7 mm and on which a recess is formed and a cover substrate 4 having a thickness of 1 mm to 7 mm to be bonded to the base substrate 3. For example, both the base substrate 3 and the cover substrate 4 are made from a transparent base material.
(226) A microchannel 203 is formed between the base substrate 3 and the cover substrate 4 bonded together with an adhesive. The microchannel 203 includes: a sample measuring section 201 made up of a capillary channel and which quantitatively measures a fixed amount of a sample liquid to be analyzed; and a receiving section 202 connected to the sample measuring section 201 and which accepts the fixed amount of the sample liquid measured by the sample measuring section 201 and causes a reaction with a reagent. Specifically, a reagent is contained in the receiving section 202 so that a reaction immediately occurs once the sample liquid is transferred to the receiving section 202. The reagent may either be a solid reagent or a reagent applied to a wall face. For example, glucose oxidase or glucose dehydrogenase for glucose measurement, cholesterol esterase or cholesterol hydrogenase for cholesterol measurement, and the like may be used as the reagent.
(227) The inlet 206a is formed on a sample collecting section 206 on one end of the sample measuring section 201. Another end of the sample measuring section 201 is connected to the receiving section 202. The sample collecting section 206 is formed so as to have an arc-like shape with a width Wc as its diameter.
(228) The sample measuring section 201 is made up of: a capillary channel primary segment 207a with a gap that is uniform in a direction towards the receiving section 202 from the sample collecting section 206 (direction depicted by arrow F); and a connected section 207b between the receiving section 202 and a trailing end position P1 of the primary segment 207a. More specifically, the connected section 207b of the sample measuring section 201 is molded as an inclined face 205 whose bottom face is an elliptical arc of a recess of the base substrate 3. A capillary channel is widely configured towards the receiving section 202.
(229) In
(230) A part of or all of wall faces of the base substrate 3 and the cover substrate 4 have been subjected to hydrophilic treatment in order to reduce viscous resistance within the microchannel 203 and promote fluid movement. Specifically, any of a bottom (the side of the base substrate 3) or a ceiling (the side of the cover substrate 4) of the sample measuring section 201 and the receiving section 202 is formed by a continuous plane subjected to hydrophilic treatment.
(231) In this case, hydrophilicity refers to a contact angle of less than 90 degrees with respect to water, and more favorably, a contact angle of less than 40 degrees. Specifically, methods of such hydrophilic treatment include a surface treatment method using plasma, corona, ozone, or an active gas such as fluorine, and surface treatment with a surfactant. Alternatively, a hydrophilic material such as glass may be used for at least one of the base substrate 3 and the cover substrate 4, or a hydrophilizing agent such as a surfactant, a hydrophilic polymer, and a hydrophilic powder such as a silica gel may be added when molding at least one of the base substrate 3 and the cover substrate 4 so as to impart a material surface with hydrophilicity.
(232) A process in which a sample liquid is collected in the analyzing device 1E created as described above and a fixed amount is measured is illustrated in
(233) In
(234) Next, as illustrated in
(235) This occurs because a part of a wall face of the sample measuring section 201 which has been continuous in a flowing direction of the sample liquid is severed by the inclined face 205, resulting in a decrease in a wet interfacial tension component due to the sample liquid flowing in a direction of the receiving section 202 and breaking the capillary force that had been previously dominant. Furthermore, as illustrated in
(236) Moreover, in the present embodiment, a face of the microchannel 203 which opposes the inclined face 205 is either made of a hydrophilic material or has been subjected to hydrophilic treatment for imparting hydrophilicity.
(237) An effect of the present eighth embodiment will now be described based on specific dimensions.
(238) At the receiving section 202 of the analyzing device 1E, when causing a reaction between the sample liquid and a reagent disposed in the receiving section 202 to measure absorbance, 10 μL of the sample liquid must be collected at the sample measuring section 201. In addition, for the purpose of improving analytical precision, it is required that quantitative variance at the sample measuring section 201 be kept to within ±5% or, in other words, 9.5 to 10.5 μL of the sample liquid must be collected. In this case, the shape of the sample measuring section 201 is set such that: Lc=9.8 mm; Wc=4.0 mm; and Dc=0.3 mm. Furthermore, in regards to the inclined face 205 of the connected section 207b, as illustrated in
(239) As a result, the amount of sample fluid overflowing to the receiving section 202 is 0.12 μL, sufficiently satisfying the ±5% quantitative variance for a sample liquid. A relationship between the elliptic arc shape of the inclined face 205 disposed in the sample measuring section 201 and an overflow amount of the sample liquid that overflows into the receiving section 202 is illustrated in
(240) A major axis L of the elliptical arc is set such that L1=1.0 mm while the length of the minor axis Dc2−Dc1 is varied. For example, it is shown that while the overflow amount of the sample liquid into the receiving section 202 is 0.68 μL in a case where the inclined face 205 has not been provided, by disposing the inclined face 205, the overflow amount of the sample liquid into the receiving section 202 is reduced to 0.2 μL or less. It is also shown that the overflow amount into the receiving section 202 can be suppressed by increasing the minor axis: Dc2−Dc1 of the elliptical arc.
(241) From the results described above, by disposing the inclined face 205 at the connected section 207b of the sample measuring section 201 and the receiving section 202, measurement of a sample liquid can be accurately performed solely by the shape of the sample measuring section 201. Collection of a sample liquid measured by the sample measuring section 201 is completed in this state to enable the sample liquid to be analyzed with high accuracy.
(242) The shape of the inclined face 205 may be a part of an arc with a radius of L as illustrated in
Ninth Embodiment
(243)
(244) The analyzing apparatus is configured as illustrated in
(245) A recess 116 on which is set the analyzing device 1E having collected a sample liquid is formed on a disk-like rotor 101B to be rotationally driven around a rotation axial center 107 by a rotation driving unit 106 that is a motor or the like. A penetrating hole 114 is provided in the recess 116 in correspondence to a position of a receiving section 202 of the set analyzing device 1E.
(246) An optical measurement unit 108 that accesses the receiving section 202 of the analyzing device 1E set on the rotor 101B is made up of a light source 112 and a photodetector 113 disposed with the rotor 101B in-between so as to be able to receive light that passes through the hole 114 of the rotor 101B.
(247) A control unit 109 controls a rotational speed and a rotational direction of the rotor 101B, a measurement timing of the optical measurement unit 108, and the like. More specifically, in addition to controlling the rotation driving unit 106 so as to rotate the analyzing device 1E around the rotation axial center 107 via the rotor 101B in any direction at a predetermined rotational speed, the control unit 109 is arranged so as to be capable of causing the analyzing device 1E to perform a left-right reciprocating movement centered around the rotation axial center 107 at a predetermined stop position and at a predetermined amplitude range and a predetermined frequency so as to swing the analyzing device 1E.
(248) A detection light 115 outputted from the light source 112 is transmitted through the hole 114 of the rotor 101B and through a reactant in the receiving section 202 of the set analyzing device 1E, and is received by the photodetector 113 and inputted to a computing section 110. The computing section 110 analyzes characteristics of the sample liquid from an absorption measurement result and displays the characteristics on a displaying section 111.
(249) A centrifugal transfer process and a reagent reaction process of the sample liquid measured by a sample measuring section 201 will be described with reference to
(250) After setting and fixing the analyzing device 1E whose sample measuring section 201 has been filled with a sample liquid onto the recess 116 of the rotor 101B, by rotating the rotor 101B in a direction depicted by an arrow as illustrated in
(251) The rotor 101B is swingingly moved so as to accelerate a reaction with a reagent. The swinging operation is performed by repetitively changing rotational directions of the rotor 101B. Specifically, by swingingly moving clockwise and counter-clockwise respectively over ±1 degrees in a state where the microchannel 203 of the analyzing device 1E is oriented in a nine o'clock direction as illustrated in
(252) The analyzing apparatus 100 processes a result of an absorbance measurement by the optical measurement unit 108 with the computing section 110 and displays an analysis result of characteristics of the sample liquid on the displaying section 111.
(253) As shown, since the control unit 109 instructs the rotation driving unit 106 to swingingly move the analyzing device 1E via the rotor 101B, the sample liquid can be analyzed with extremely high accuracy.
(254)
(255) While the base substrate 3 and the cover substrate 4 have been formed with a substrate thickness of 1 mm to 7 mm in the sixth and eighth embodiments described above, no limitations need be imposed as long as the substrate thickness enables the microchannel 203 to be formed. The shapes of the base substrate 3 and the cover substrate 4 also need not be limited and a shape suitable for applications and purposes such as a sector-like shape, a disk-like shape, a plate-like shape, and other complicated shapes of a molded material or the like may be adopted.
(256) In addition, while plastic has been used as the material of the base substrate 3 and the cover substrate 4 in the sixth and eighth embodiments described above from the perspectives of moldability, high productivity, and low cost, no limitations need be imposed as long as a bondable material such as glass, a silicon wafer, metal, and ceramic is used.
(257) In the sixth and eighth embodiments described above, while the cover substrate 4 and the base substrate 3 are bonded using an adhesive, bonding may be achieved by such bonding methods as fusion joining, anodic bonding, and laser bonding according to the materials used.
Tenth Embodiment
(258) A rectangular shape of a leading end of a spot application section according to the respective embodiments described above disadvantageously causes a sample liquid to adhere to external wall faces of an analyzing device other than the spot application section during spot application. However, with an analyzing device 1F according to the present tenth embodiment, a proximal end of a spot application section 13A is connected to a capillary cavity 131 and a leading end thereof protrudes from a cover substrate 4, and a shape of the leading end of the spot application section 13A is formed as a hemisphere that protrudes in a direction away from a channel forming face of a base substrate 3.
(259) As illustrated in
(260) The cover substrate 4 includes an inlet 13B, a rib 13C, and an air open hole 136. The base substrate 3 includes the spot application section 13A, the capillary cavity 131, a holding chamber 132, a channel 8, a measurement chamber 133, a channel 9, and an outlet port 130.
(261) In the analyzing device 1F, a predetermined amount of a sample liquid such as blood injected into the inlet 13B is temporarily held in the holding chamber 132 via the capillary cavity 131. The holding chamber 132 holds an analytical reagent (not shown). The sample liquid and the analytical reagent are mixed, and the mixed liquid is transferred to the measurement chamber 133 via a capillary cavity 8. The measurement chamber 133 communicates with a capillary cavity 9 having the air open hole 136. Predetermined items of the mixture of the sample liquid and the analytical reagent transferred to the measurement chamber 133 are measured and analyzed by an optical method.
(262) As for the shape of the spot application section 13A according to the present embodiment, a proximal end is connected to the capillary cavity 131 and a leading end protrudes from a cover substrate 4. A shape of the leading end of the spot application section 13A is formed as a hemisphere that protrudes in a direction away from a channel forming face of a base substrate 3. Specifically, as illustrated in
(263) At this point, by superimposing the cover substrate 4 on the base substrate 3, a shape is formed in which the leading end of the spot application section 13A protrudes from the inlet 13B of the cover substrate 4 so as to enable spot application of a sample liquid to be performed easily.
(264) In addition, a diameter D of the inlet 13B and the spot application section 13A is set equal to or slightly greater than a droplet of the sample liquid that is a measurement object, thereby enabling the sample liquid to flow in from any portion of the inlet 13B when spot-applying the sample liquid. Due to such a setup, a configuration capable of causing the adhered sample liquid to entirely flow into the capillary cavity is realized.
(265) In this case, as for a droplet diameter of a sample liquid, when the sample liquid is blood, an amount of blood appearing on a fingertip pierced by a puncture device is approximately 10 μL. Since a diameter of blood in this amount is around 4 mm, a diameter D of the inlet 13B and the spot application section 13A is favorably arranged so as to be around 4 mm which is equal to a blood droplet diameter or to be around 5 mm which is slightly greater.
(266) Furthermore, providing the rib 13C on the cover substrate 4 so as to surround the spot application section 13A has an effect of preventing a finger or the like from coming into contact with locations other than the spot application section 13A and preventing blood from adhering to such locations during spot application. A height of the rib 13C is set lower than the spot application section 13A. This is because if the height of the rib 13C is greater than the spot application section 13A, a sample liquid cannot be suctioned when a fingertip is pressed against the inlet 13B to completely cover the inlet 13B. The rib 13C is integrally resin-molded with the cover substrate 4. A surface of the rib 13C molded from a synthetic resin material is able to repel blood due to a water-shedding quality of the synthetic resin material itself.
(267) When mixing of the reagent and the sample liquid reaches a predetermined level, a sample liquid in the holding chamber 132 is carried to an inlet port of the measurement chamber 133 by a capillary force through a channel 8, and is then transferred into the measurement chamber 133 utilizing a centrifugal force generated by rotating the analyzing device 1F at a predetermined number of revolutions. A predetermined item of the transferred sample liquid is optically measured at the measurement chamber 133.
(268) A measurement of the sample liquid involves irradiating light on the measurement chamber 133 and optically analyzing a reactive state of the liquid sample to be tested and an analytical reagent. Since absorbance varies according to a ratio of a reaction between a sample liquid and an analytical reagent, a predetermined item can be measured and a reactive state can be analyzed by measuring an absorbance of light to be irradiated. In the present embodiment, a sample liquid is held in the holding chamber 132 by a capillary force via the capillary cavity 131 that leads to the inlet 13B.
(269) Wall faces of channels 134 and 135 have been subjected to hydrophilic treatment. Methods of such hydrophilic treatment include a surface treatment method using plasma, corona, ozone, or an active gas such as fluorine, and surface treatment with a surfactant or a hydrophilic polymer. In this case, hydrophilicity refers to a contact angle with water that is less than 90 degrees.
(270) An effect according to the present embodiment will be described.
(271) A specific example of dimensions of the analyzing device 1F will be described.
(272) In this case, as illustrated in
(273) A size of the analyzing device 1F can be varied as appropriate to achieve a suitable size as a sample liquid collecting section. In addition, a thickness of the capillary cavity 131 forming a channel of the sample liquid or, in other words, a channel depth is set to 0.1 mm. On the other hand, a depth of the holding chamber 132 coupled to the capillary cavity 131 and formed on the base substrate 3 of the analyzing device 1F is formed deeper than the thickness of the capillary cavity 131 (i.e., eventual channel depth) so as to be 0.3 mm to 0.5 mm. Due to such a configuration, a sample liquid injected into the capillary cavity 131 does not proceed to the holding chamber 132 by a capillary force alone and is transferred utilizing a centrifugal force obtained by rotating the analyzing device 1F. It is obvious that a similar effect can be obtained by cross-sectional shapes of the capillary cavity 131 other than a rectangular shape such as a circular shape and an elliptic shape as long as the shape enables capillary force to act.
(274) While depths of the capillary cavity 131 and the channels 134 and 135 according to the present invention are formed so as to be equal to or greater than 0.02 mm and less than 0.3 mm, such dimensions are not restrictive as long as a sample liquid flows by a capillary force. Generally, since a liquid such as blood is to be measured and analyzed, depths are desirably set so as to equal to or greater than 0.02 mm and less than 0.3 mm. In addition, while the depths of the holding chamber 132 and the measurement chamber 133 are formed so as to range from 0.3 mm to 0.5 mm, the depths can be adjusted according to a sample solution volume and conditions for measuring absorbance (optical path length, measured wavelength, reaction concentration of sample solution, reagent type, and the like). Subsequently, a sample liquid transferred to the measurement chamber 133 is optically measured.
(275)
(276) Reference characters (a-1) and (a-2) in
(277)
(278) In
(279) However, from
(280)
(281) As illustrated in
(282) From the description above, it is confirmed that a sample liquid can be made to adhere only to a spot application section by arranging a leading end of the spot application section so as to have a hemispherical shape.
Eleventh Embodiment
(283) With the analyzing devices according to the respective, embodiments described above, when injecting a sample from a sample injection tool such as a syringe, a dropper, or a pipette, it is required that a leading end of the sample injection tool is brought into contact with a sample inlet of the analyzing device, and the sample must be suctioned by a capillary force by spot-applying small amounts of the sample a number of times which can be held at the outside of the inlet by surface tension. Alternatively, a sample must be dropped from a sample injection tool onto a sheet-like test specimen made of plastic or glass and suctioned by bringing a sample inlet of an analyzing device into contact with the dropped sample. However, by forming a plurality of inlets as is the case with an eleventh embodiment on the analyzing devices according to the respective embodiments described above, a mode of injection using a sample injection tool can be accommodated in addition to direct spot application.
(284)
(285)
(286) The analyzing device 1G is configured by a bonding of a cover substrate 4 and a base substrate 3. A microchannel structure having minute irregularities is formed on a face of the base substrate 3 and is arranged so that various functions such as sample liquid transfer and retention of a predetermined liquid amount are carried out. The cover substrate 4 and the base substrate 3 are to be bonded by a well known bonding method such as ultrasonic bonding and UV adhesion. After bonding, a protective cap 2 is attached that is openable and closable around a shaft 6a in order to prevent scattering of a sample liquid.
(287) A first inlet 13a is an inlet port-side opening made up of a groove-like first capillary cavity 140 formed on the base substrate 3 and a convex protrusion 4b (refer to
(288) A second inlet 141 is made up of a recess 141b formed on the base substrate 3 and a hole 141a formed on the cover substrate 4 and which communicates with the recess 141b. In an in-use state, an opening of the hole 141a is covered and closed by a lid 41a formed on the protective cap 2.
(289)
(290)
(291) As illustrated in
(292) By forming the recess 161 so as to have a gently curving structure in which a sectional area of an axial center-side opening of the recess is equal to or greater than a sectional area of a circumferentially outward opening of the recess, a sample liquid having adhered to a periphery of the first inlet 13a is reliably transferred to the rear of the recess 161 by a centrifugal force accompanying a rotation of the rotor 101, and becomes more likely to be transferred to a lowermost location of the recess 161. Therefore, the sample liquid can be collected without being scattered to the outside of the recess 161.
(293) As illustrated in
(294) Hereinafter, in regards to a specific sample liquid measurement method of the analyzing apparatus 100 according to the present invention, procedures up to an insertion of the analyzing device 1G into the analyzing apparatus will be described with reference to
(295) Before mounting the analyzing device 1G onto the analyzing apparatus 100, a user injects a sample liquid into the analyzing device 1G through the first inlet 13a or through the second inlet to be described later. Subsequently, as illustrated in
(296) By inserting the analyzing device 1G into the analyzing device holding member 154 and closing the door 149, the analyzing device holding member 154 returns to a position depicted by an imaginary line and holds the analyzing device 1G at a predetermined position on the rotor 101.
(297) Subsequently, the user operates an operating section 308 at which an operating button for instructing a start of measurement and the like are arranged to start a measurement of a sample liquid component. An instruction from a user is interpreted at the central processing section 301. The motor 143 is driven by the drive control section 302 to rotate and/or stop the analyzing device 1G, and utilizing a centrifugal force and/or a capillary force, an analysis object is eventually introduced into a measurement chamber 133 (refer to
(298) Prior to the introduction to the measurement chamber 133, an enzymatic reaction has been caused between blood plasma and a reagent (not shown) made up of an enzyme, a pigment, a buffer and the like disposed in the holding chamber 132 of the analyzing device 1G and a color reaction is given. At this point, melting and agitation can be promoted by varying the number of revolutions of the motor 143 from, for example, 500 rpm to 1500 rpm so as to apply acceleration or by repeating positive and negative rotational movements from clockwise to counter-clockwise. The color-reacted reaction liquid is transferred to the measurement chamber 133 and irradiated by a light source 147 via the hole 128, whereby a transmitted light is detected by a detector 146. Absorbance is determined from a ratio of reflected light against incident light, and based on a calibration curve held in a memory 309, a concentration of a specific component is computed by the central processing section 301 and displayed on a displaying section 307.
(299) In addition, when the sample liquid is a blood specimen, temperature dependence is generally high and affects measurement time and measurement accuracy. Therefore, preferably, at least the temperature after starting a reagent reaction is kept constant (30° C. to 37° C.). To this end, with the analyzing apparatus 100, heaters 150a to 150d are controlled by a temperature control section 306 based on a detection result of a temperature data processing section 305 of a temperature sensor 155 to manage the air temperature inside the housing space in order to set the temperature to at least 37° C. upon start of the reaction with the reagent. By keeping the air temperature inside the housing constant in this manner, the analyzing device 1G can be uniformly heated without unevenness.
(300) Moreover, depending on applications, depending on configurations of chambers and channels inside the analyzing device 1G, the analyzing apparatus 100 can also become a centrifugal separator that transfers and centrifugally separates a liquid inside the analyzing device 1G utilizing a centrifugal force generated by a rotation around an axial center.
(301) The analyzing device 1G may have a sector-like shape, a cubic shape, or any other shape. A plurality of analyzing devices 1G may be simultaneously mounted on the rotor 101.
(302) Next, a microchannel configuration of the analyzing device 1G and a sample liquid transfer process according to the present eleventh embodiment will be described in detail.
(303)
(304) As illustrated in
(305) In this case, while depths of the first capillary cavity 140 and the channels 134 and 135 are formed so as to range from 50 μm to 300 μm, such dimensions are not restrictive as long as a sample liquid flows by a capillary force. While the depths of the holding chamber 132, the measurement chamber 133, and the cavities 24 and 16 are formed so as to range from 0.3 mm to 5 mm, the depths can be adjusted according to a sample solution volume and conditions for measuring absorbance (optical path length, measured wavelength, reaction concentration of sample solution, reagent type, and the like).
(306) In order to cause a sample liquid to flow by a capillary force, wall faces of the first capillary cavity 140 and channels 134 and 135 have been subjected to hydrophilic treatment. Methods of such hydrophilic treatment include a surface treatment method using plasma, corona, ozone, or an active gas such as fluorine, and surface treatment with a surfactant or a hydrophilic polymer. In this case, hydrophilicity refers to a contact angle of less than 90 degrees with respect to water, and more favorably, a contact angle of less than 40 degrees.
(307) —Transfer Process when Sample Liquid is Introduced into the First Inlet 13a—
(308) A transfer process in this case is to be executed as illustrated in
(309) In order to supply a sample liquid to the analyzing device 1G, a sample liquid is spot-applied to the first inlet 13a from a lateral face of the analyzing device 1G before setting the analyzing device 1G on the analyzing apparatus 100. Immediately after spot application, as illustrated in
(310) At this point, since the cavity 24 for discharging air inside the first capillary cavity 140 is provided on a lateral face of the first capillary cavity 140, the sample liquid becomes a capillary flow in which a central portion of the first capillary cavity 140 precedingly flows instead of a capillary flow in which lateral face-portions of the first capillary cavity 140 precedingly flows, and fills the inside of the first capillary cavity 140. Therefore, even if the sample liquid spot-applied to the first inlet 13a runs out while the first capillary cavity 140 is being filled or if the sample liquid is inadvertently detached from the first inlet 13a while the first capillary cavity 140 is being filled, by recommencing spot-application from the first inlet 13a, the sample liquid at the central portion of the first capillary cavity 140 precedingly flows and comes into contact with a central portion of a sample liquid held in the capillary cavity, and proceeds to fill the capillary cavity while discharging air in a lateral face-direction in which the cavity 24 exists. Therefore, air bubbles are not generated, and spot-applications can be repeatedly performed until a predetermined amount of the sample liquid is held by the first capillary cavity 140.
(311) As for the first capillary cavity 140 and the cavity 24, the cavity 24 whose cross-sectional dimension in the thickness direction is greater than the cross-sectional dimension of the first capillary cavity 140 is provided on a lateral face on one side of the rectangular first capillary cavity 140 formed on the base substrate 3 as illustrated in
(312) With the configuration illustrated in
(313) After the first and second capillary cavities 140 and 156 are filled with the sample liquid, by setting the analyzing device 1G in a state where the protective cap 2 is closed as illustrated in
(314) The sample liquid having flowed into the holding chamber 132 is mixed with the analytical reagent held in the holding chamber 132 by a swinging motion caused by acceleration of a rotation of the analyzing apparatus 100 or by liquid diffusion during suspension of rotation. However, mixing may alternatively be performed by applying an external force that directly vibrates the holding chamber itself.
(315) Next, when mixing of the reagent and the sample liquid reaches a predetermined level, as illustrated in
(316) Subsequently, as illustrated in
(317) —Transfer Process when Sample Liquid is Introduced into the Second Inlet 141—
(318) A transfer process in this case is to be executed as illustrated in
(319) In this case, before setting the analyzing device 1G on the analyzing apparatus 100, a user spot-applies a sample liquid into the widely opened hole 141a of the second inlet 141 using a sample injection tool such as a syringe, a dropper or a pipette. Immediately after spot application, as illustrated in
(320) At this point, as illustrated in
(321) After the first and second capillary cavities 140 and 156 are filled with the sample liquid, by setting the analyzing device 1G in a state where the protective cap 2 is closed as illustrated in
(322)
(323) Regarding subsequent transferring of a reagent liquid, since
(324) By providing an air open hole that communicates with a summit of the second capillary cavity 156, a quantitativity of the sample liquid to be transferred to the holding chamber 132 can be further improved.
(325) Moreover, the motor 143, the shaft 151, couplings 144a and 144b for coupling the motor 143 and the shaft 151, the rotor 101, the rotor holding member 152, the drive control section 302 that controls the motor 143, and the central processing section 301 that controls the drive control section 302 illustrated in
(326) The detector 146, the light source 147, a signal processing section 304 that converts a transmitted light detected by the detector 146 into an electrical signal, a light source control section 303 that controls outputted light of the light source 147, and the central processing section 301 that controls the signal processing section 304 and the light source control section 303 and which calculates an absorbance illustrated in
Twelfth Embodiment
(327)
(328) Parts achieving the same effects as those illustrated in
(329) As illustrated in
(330) As illustrated in
(331) Moreover, in the present twelfth embodiment, a width W4 of the protrusion 242 of the base substrate 3 in a vicinity of the opening 240 and a width W5 of the protrusion 243 of the cover substrate 4 in a vicinity of the opening 240 are formed so as to equal each other.
(332) In addition, wall faces of the supplying capillary channel 17a, a holding chamber 19a, and channels 134 and 135 have been subjected to hydrophilic treatment. Methods of hydrophilic treatment include a surface treatment method using plasma, corona, ozone, or an active gas such as fluorine, and surface treatment with a surfactant or a hydrophilic polymer. In this case, hydrophilicity refers to a contact angle with water that is less than 90 degrees.
(333) As for specific dimensions of the analyzing device 1H, a thickness of the base substrate 3 is 15 mm, a thickness of the cover substrate 4 is 1 mm, and when the analyzing device 1H is arranged as an approximately 80 mm square, a depth of the holding chamber 19a is 0.1 mm. A depth of a reagent chamber 132a is formed deeper than a depth of the holding chamber 19a so as to range from 0.3 mm to 0.5 mm. Due to such a configuration, blood injected into the holding chamber 19a does not proceed to the reagent chamber 132a by a capillary force alone and the sample liquid is transferred utilizing a centrifugal force obtained by rotating the analyzing device 1H.
(334) While depths of the supplying capillary channel 17a, the holding chamber 19a, and the channels 134 and 135 are formed so as to be equal to or greater than 0.02 mm and less than 0.3 mm, such dimensions are not restrictive as long as a sample liquid flows by a capillary force. Generally, since a liquid such as blood is to be measured and analyzed, depths are desirably set so as to equal to or greater than 0.02 mm and less than 0.3 mm. In addition, while the depths of the reagent chamber 132a and the measurement chamber 133 are formed so as to range from 0.3 mm to 0.5 mm, the depths can be adjusted according to a sample solution volume and conditions for measuring absorbance (optical path length, measured wavelength, reaction concentration of sample solution, reagent type, and the like). Subsequently, a sample liquid transferred to the measurement chamber 133 is optically measured.
(335) The width W4 of the protrusion 242 of the base substrate 3 and the width W5 of the protrusion 243 of the cover substrate 4 are set so as to range from 3 to 5 mm, and a protrusion length L3 of the spot application section 13A from an analyzing device main body 241 is set to 8 mm.
(336) Due to such a configuration, when performing an analysis of blood as a sample liquid, as is the case with the analyzing device 1H depicted by an imaginary line in
(337) Therefore, by inclining the analyzing device 1H as depicted by a solid line in
(338) As shown, by forming the shape of the leading end of the spot application section 13A as the inclined face 244, as illustrated in
(339) Accordingly, occurrences of situations of insufficiency where blood held in the holding chamber 19b fails to reach a fixed amount can be reduced, and an accurate analysis can be performed when blood held in the holding chamber 19a is transferred towards the measurement chamber 133 by a centrifugal force and a solution in the measurement chamber 133 is optically accessed and analyzed.
Thirteenth Embodiment
(340)
(341) In the case of the twelfth embodiment, it is conceivable that when the analyzing device 1H is excessively pressed against the fingertip 120 of a testee as illustrated in
(342) Due to such a configuration, even when the analyzing device 1H is excessively pressed against a fingertip 120 of a testee, as illustrated in
Fourteenth Embodiment
(343)
(344) In the twelfth embodiment, since the inclined face 244 is formed at the spot application section 13A, an area wetted by blood when the inclined face 244 is brought into contact with the blood drop 121 increases in comparison to a comparative example illustrated in
(345) In the twelfth embodiment, the width W4 of the protrusion 242 of the base substrate 3 and the width W5 of the protrusion 243 of the cover substrate 4 are formed so as to equal each other. However, in the present fourteenth embodiment, while an incline of the inclined face 244 of the spot application section 13A is the same, a width W5 of a protrusion 243 of a cover substrate 4 in a vicinity of the opening 240 is formed narrower than a width W4 of a protrusion 242 of a base substrate 3. In
(346) Due to such a configuration, blood is first suctioned by a capillary force into a holding chamber 19a via a supplying capillary channel 17a as illustrated in
(347) In the twelfth, thirteenth, and fourteenth embodiments, the more acute the incline of the spot application section, the more the analyzing device 1H can be inclined horizontally, which is effective in reducing filling time. While an incline of the spot application section 13A ranging from 30 to 45 degrees has been confirmed effective when blood is used as a sample liquid, the angle is not restricted thereto if an angle of 45 degrees or greater is effective in regards to filling time depending on the sample liquid.
(348) While the case of an analyzing device to be used for reading involving optically accessing a solution in the measurement chamber 133 has been described as an example in the twelfth, thirteenth, and fourteenth embodiments, an analyzing device to be used for reading involving accessing a solution in the measurement chamber 133 provided with an electrochemical sensor can be similarly implemented.
(349) In addition, while the case where blood suctioned by a capillary force into the holding chamber 19a is transferred by a centrifugal force to the measurement chamber 133 has been described as an example in the twelfth, thirteenth, and fourteenth embodiments, even in a case of an analyzing device to be used for reading involving directly suctioning a sample liquid from the opening 240 into a measurement chamber having a capillary force and accessing a test object in the measurement chamber, the fixed amount of blood can be sampled and an accurate analysis can be realized by forming a shape of a leading end of the spot application section 13A as the inclined face 244 as described in the twelfth, thirteenth, and fourteenth embodiments.
Fifteenth Embodiment
(350) In a case where a spot application section of an analyzing device is directly brought into contact with a blood drop 121 to suction and sample blood by a capillary force, an insufficient amount of blood is sampled to an analyzing device when the contact time of the spot application section to the blood drop is short. Fifteenth to twenty-first embodiments will describe, based on specific examples, specific configurations in which analyzing devices according to the respective embodiments described above are provided with a confirmation window that enables a sampling amount to be visually confirmed.
(351)
(352) An analyzing device 1J is constructed by a bonding of a base substrate 3 and a cover substrate 4 illustrated in
(353) An internal recess to become a holding chamber 19a, a reagent chamber 132a, a channel 134, a measurement chamber 133, and a channel 135 is formed on a bonding face 3a of the base substrate 3 with the cover substrate 4. The reagent chamber 132a holds an analytical reagent (not shown). The cover substrate 4 molded from a transparent synthetic resin covers respective opening faces of the internal recess so as to form a cavity having a predetermined gap so as to realize respective functions such as transferring of a sample liquid by a capillary force and retention of a predetermined liquid volume. Reference character 136b denotes an air open hole formed on the cover substrate 4 in correspondence to a position of an outlet port 136a on a side of the base substrate 3.
(354) In addition, wall faces of a supplying capillary channel 17a, the holding chamber 19a, and the channels 134 and 135 have been subjected to hydrophilic treatment. Methods of hydrophilic treatment include a surface treatment method using plasma, corona, ozone, or an active gas such as fluorine, and surface treatment with a surfactant or a hydrophilic polymer. In this case, hydrophilicity refers to a contact angle with water that is less than 90 degrees.
(355) As for specific dimensions of the analyzing device 1J, a thickness of the base substrate 3 is 15 mm, a thickness of the cover substrate 4 is 1 mm, and when the analyzing device 1J is arranged as an approximately 80 mm square, a depth of the holding chamber 19a is formed so as to be equal to or greater than 0.02 mm and less than 0.3 mm. The depth of the holding chamber 19a when measuring and analyzing a liquid such as blood is preferably 0.1 mm. A depth of the reagent chamber 132a is formed deeper than the depth of the holding chamber 19a so as to be greater than 0.3 mm and equal to or less than 0.5 mm. Due to such a configuration, blood injected into the holding chamber 19a does not proceed to the reagent chamber 132a by a capillary force alone and the sample liquid is transferred utilizing a centrifugal force obtained by rotating the analyzing device 1J.
(356) While depths of the supplying capillary channel 17a, the holding chamber 19a, and the channels 134 and 135 are formed so as to be equal to or greater than 0.02 mm and less than 0.3 mm, such dimensions are not restrictive as long as a sample liquid flows by a capillary force. In addition, while the depths of the reagent chamber 132a and the measurement chamber 133 are formed so as to be greater than 0.3 mm and equal to or less than 0.5 mm, the depths can be adjusted according to a sample solution volume and conditions for measuring absorbance (optical path length, measured wavelength, reaction concentration of sample solution, reagent type, and the like). Subsequently, a sample liquid transferred to the measurement chamber 133 is optically measured.
(357) The spot application section 13A is formed by a bonding of a protrusion 242 of the base substrate 3 and a protrusion 243 of the cover substrate 4. As illustrated in
(358) When blood is used as a sample liquid, all of gaps of the supplying capillary channel 17a and most gaps of the holding chamber 19a are formed so as to be, for example, less than 0.3 mm, and a gap of the reagent chamber 132a is formed so as to be greater than 0.3 mm and equal to or less than 0.5 mm.
(359) The only difference from the comparative example illustrated in
(360) The difference from the comparative example is that, as illustrated in
(361) In addition, as illustrated in
(362) Due to such a configuration, when performing an analysis of blood as a sample liquid, by setting the analyzing device 1J to a vertical posture and bringing the spot application section 13A into contact with a blood drop 121 on a fingertip 120 of a testee, as illustrated in
(363) Once suctioned blood reaches a fixed amount, the suctioned blood reaches the filling confirmation region 246 as illustrated in
(364) In the case of the comparative example illustrated in
(365) While the protrusion 247 is provided on the side of the base substrate 3 and the gap is formed so as to be 0.1 mm in the present fifteenth embodiment, the protrusion 247 may alternatively be provided on the side of the cover substrate 4 and an 0.1 mm gap may be formed on a trailing end of the holding chamber 19a.
Sixteenth Embodiment
(366)
(367) As illustrated in
(368) Since the leading end of the spot application section 13A is formed on the inclined face 244, in the spot application section 13A formed by a bonding of a protrusion 242 of the base substrate 3 and a protrusion 243 of the cover substrate 4, a protrusion length L4 of the protrusion 243 is smaller than a protrusion length L3 of the protrusion 242. In addition, as illustrated in
(369) Moreover, a width W4 of the protrusion 242 of the base substrate 3 in a vicinity of the opening 240 and a width W5 of the protrusion 243 of the cover substrate 4 in a vicinity of the opening 240 are formed so as to equal each other.
(370) The width W4 of the protrusion 242 of the base substrate 3 and the width W5 of the protrusion 243 of the cover substrate 4 are set so as to range from 3 to 5 mm, and a protrusion length L3 of the spot application section 13A from an analyzing device main body 241 is set to 8 mm.
(371) The spot application section 13A is formed by a bonding of the protrusion 242 of the base substrate 3 and the protrusion 243 of the cover substrate 4. Configurations of a filling confirmation region 246 on a trailing end of the holding chamber 19a and a confirmation window 253 are the same as the fifteenth embodiment, and as illustrated in
(372) Due to such a configuration, when performing an analysis of blood as a sample liquid, as is the case with the analyzing device 1K depicted by an imaginary line in
(373) Therefore, by inclining the analyzing device 1K as depicted by a solid line in
(374) As shown, by forming the shape of the leading end of the spot application section 13A on the inclined, face 244, as illustrated in
(375) Furthermore, when suctioned blood reaches a fixed amount, the suctioned blood reaches the filling confirmation region 246, thereby enabling the suctioned blood to be confirmed from the confirmation window 253. Therefore, an accurate analysis can be performed when blood held in the holding chamber 19a is transferred towards the measurement chamber 133 by a centrifugal force and a solution in the measurement chamber 133 is optically accessed and analyzed.
Seventeenth Embodiment
(376)
(377) In the case of the sixteenth embodiment, it is conceivable that when the analyzing device 1K is excessively pressed against the fingertip 120 of a testee as illustrated in
(378) Configurations of a filling confirmation region 246 on a trailing end of a holding chamber 19a and the confirmation window 253 are the same as the fifteenth embodiment, and as illustrated in
(379) Due to such a configuration, even when the analyzing device 1K is excessively pressed against a fingertip 120 of a testee, as illustrated in
Eighteenth Embodiment
(380)
(381) In the sixteenth embodiment, since the inclined face 244 is formed at the spot application section 13A, an area wetted by blood when the inclined face 244 is brought into-contact with the blood drop 121 increases in comparison to a comparative example illustrated in
(382) In the sixteenth embodiment, the width W4 of the protrusion 242 of the base substrate 3 and the width W5 of the protrusion 243 of the cover substrate 4 are formed so as to equal each other. However, in the present seventeenth embodiment, while an incline of the inclined face 244 of the spot application section 13A is the same, a width W5 of a protrusion 243 of a cover substrate 4 in a vicinity of the opening 240 is formed narrower than a width W4 of a protrusion 242 of a base substrate 3. In
(383) Configurations of a filling confirmation region 246 on a trailing end of a holding chamber 19a and the confirmation window 253 are the same as the fifteenth embodiment, and as illustrated in
(384) Due to such a configuration, blood is first suctioned by a capillary force into a holding chamber 19a via a supplying capillary channel 17a as illustrated in
(385) In the respective embodiments described above, the more acute the incline of the spot application section, the more the analyzing device 1K can be inclined horizontally, which is effective in reducing filling time. While an incline of the spot application section 13A ranging from 30 to 45 degrees has been confirmed as being effective when blood is used as a sample liquid, the angle is not restricted thereto if an angle of 45 degrees or greater is effective in regards to filling time depending on the sample liquid.
Nineteenth Embodiment
(386)
(387) In the fifteenth embodiment, the protrusion 247 that forms the filling confirmation region 246 having a smaller gap (0.1 mm) than the capillary force-generating gap (0.3 mm) of the holding chamber 19a is formed on a trailing end of the holding chamber 19a. However, the present nineteenth embodiment differs from the fifteenth embodiment in that, as illustrated in
(388) Due to such a configuration, as illustrated in
(389) Once the suctioned blood reaches a fixed amount, as illustrated in
(390) Moreover, while the nineteenth embodiment is an embodiment in which the filling confirmation region 246 formed as the protrusion 247 in the fifteenth embodiment is now formed as the recess 250, the nineteenth embodiment may alternatively be implemented by forming the filling confirmation region 246 formed as the protrusion 247 in the sixteenth, seventeenth, and eighteenth embodiments as the recess 250.
Twentieth Embodiment
(391)
(392) In the nineteenth embodiment, the gap provided on the trailing end of a holding chamber 19a and which is greater than the capillary force-generating gap of the holding chamber 19a is formed between the bottom of the recess 250 that penetrates on a side of the base substrate 3 towards an opposite side to the cover substrate 4 and the cover substrate 4. However, the present twentieth embodiment differs from the nineteenth embodiment in that a recess 251 is formed on the cover substrate 4 so as to correspond to a recess 250 formed on a side of a base substrate 3.
(393) As illustrated in
(394) In contrast, by forming the recess 251 on the cover substrate 4 as is the case with the twentieth embodiment, occurrences of situations where blood that is a sample liquid flows along a face of the cover substrate 4 and penetrates into the recess 250 can be avoided even when a diameter of the recess 250 is small. As a result, a fixed amount display viewed from a confirmation window 253 can be clarified.
Twenty-First Embodiment
(395)
(396) In the twentieth embodiment illustrated in
(397) Even in this case, a fixed amount display viewed from a confirmation window 253 can be clarified in the same manner as in the twentieth embodiment.
(398) In the respective embodiments described above, the confirmation window 253 is provided on a side of the base substrate 3. Alternatively, the respective embodiments described above may be arranged such that the confirmation window 253 is provided on a side of the cover substrate 4 in correspondence to the filling confirmation region 246.
(399) While the case of an analyzing device to be used for reading involving optically accessing a solution in the measurement chamber 133 has been described as an example in the respective embodiments described above, an analyzing device to be used for reading involving accessing a solution in the measurement chamber 133 provided with an electrochemical sensor can be similarly implemented.
(400) In addition, while the case where blood suctioned by a capillary force into the holding chamber 19a is transferred by a centrifugal force to the measurement chamber 133 has been described as an example in the fifteenth to twenty-first embodiments, even in a case of an analyzing device to be used for reading involving directly suctioning a sample liquid from the opening 240 into a measurement chamber having a capillary force and accessing a test object in the measurement chamber, the fixed amount of blood can be sampled and an accurate analysis can be realized by enabling blood suctioned into the holding chamber 19a to be confirmed from the confirmation window 253 as described in the fifteenth to twenty-first embodiments.
INDUSTRIAL APPLICABILITY
(401) The present invention is useful as, for example, a transfer control unit of an analyzing device to be used for component analysis of a liquid collected from a living organism or the like.