Source: http://www.freepatentsonline.com/7201042.html
Timestamp: 2018-03-18 02:21:17
Document Index: 75456670

Matched Legal Cases: ['art 21', 'art 22', 'art 23', 'art 24', 'art 25', 'art 26', 'art 21', 'art 21', 'art 21', 'art 22', 'art 21', 'art 22', 'art 22', 'art 23', 'art 23', 'art 33', 'art 33', 'art 23', 'art 23']

Measuring instrument provided with solid component concentrating means - Arkray, Inc.
United States Patent 7201042
The present invention relates to a measuring instrument (1) comprising a channel (60) for moving a sample liquid (BL) containing a solid component (B1) and providing a liquid reaction field and first and second electrodes (31, 32) which are used to apply voltage to the liquid reaction field. The first electrode (31) has an electron transfer interface (31a) for transferring electrons between it and the liquid reaction field when voltage is applied to the liquid reaction field via the first and second electrodes (31, 32). The measuring instrument (1) comprises concentrating means (51) for increasing the concentration of solid components at portions thereof which contact the electron transfer interface (31a) in the liquid reaction field. The concentrating means (51) preferably comprises a water-absorbing layer containing an absorbent polymer material.
Yamaoka, Hideaki (Kyoto, JP)
Katsuki, Koji (Kyoto, JP)
10/533602
73/64.56, 204/403.06, 324/71.4
G01N15/06; C12Q1/00; G01N1/00
324/71.4, 324/449, 73/64.56, 73/865.5, 204/403.06, 73/61.71, 204/403.11, 324/71.1, 204/403.01
Download PDF 7201042 PDF help
6761816 Printed circuit boards with monolayers and capture ligands 2004-07-13 Blackburn et al. 205/777.5
6723371 Process for preparing an electrochemical test strip 2004-04-20 Chih-hui 427/2.13
6719887 Biosensor 2004-04-13 Hasegawa et al.
6391265 Devices incorporating filters for filtering fluid samples 2002-05-21 Buechler et al.
4897173 Biosensor and method for making the same 1990-01-30 Nankai et al. 204/403.05
3238452 Apparatus and method for detecting contaminants in a fluid 1966-03-01 Schmitt et al. 324/666
EP1235068 2002-08-28 BIOSENSOR
JP63058149 March, 1988 BIOSENSOR
JP03170854 July, 1991 BIOSENSOR
JP6130023 May, 1994
JP8114539 May, 1996
JP9243591 September, 1997
JP200081407 March, 2000
JP2000338076A 2000-12-08
JP2002508698A 2002-03-19
JP2002189014A 2002-07-05
JP2002202283A 2002-07-19
JP2002535615A 2002-10-22
JP2002535616A 2002-10-22
WO2000042424A1 2000-07-20 MICROFABRICATED CAPILLARY ELECTROPHORESIS CHIP AND METHOD FOR SIMULTANEOUSLY DETECTING MULTIPLE REDOX LABELS
JP2000081407A 2000-03-21
JPH06130023A 1994-05-13
JPH09243591A 1997-09-19
JPS6358149A 1988-03-12
JPH03170854A 1991-07-24
JPH08114539A 1996-05-07
Hanning, I. et al. “Improved Blood Compatibility at a Glucose Enzyme Electrode Used for Extracorporeal Monitoring”, Analyticall Letters, 19(384), 461-478 (1986).
Hanning et al. “Improved blood compatibility at glucose enzyme electrode used for extracorporeal monitoring”, Analytical Letters, vol. 19, No. 3/4, pp. 461-478 (1986).
1. A measuring instrument comprising: a channel comprising a sample inlet opening and an exhaust opening, the channel allows for moving a sample liquid containing a solid component from the sample inlet opening toward the exhaust opening and for providing a liquid reaction field; a first electrode and a second electrode which are used to apply voltage to the liquid reaction field, wherein a distance from the sample inlet opening to the first electrode is greater than a distance from the sample inlet opening to the second electrode, wherein the first electrode comprises an electron transfer interface for providing electrons to the liquid reaction field or receiving electrons from the reaction field when voltage is applied to the liquid reaction field via the first and second electrodes; a concentration means for increasing the concentration of the solid component in a part in which solid component contacts the electron transfer interface in the liquid reaction field; and a water-absorbing layer positioned only downstream from the second electrode in a flow direction of the sample liquid, wherein the water-absorbing layer allows flow of the sample liquid from the sample inlet opening toward the second electrode but restricts flow of the sample liquid from the first electrode toward the exhaust opening.
10. The measuring instrument according to claim 9, wherein the water-absorbing layer has a relative length in the flow direction of the sample liquid is ¼ to ½ of a distance from the sample inlet opening of the channel to a furthest downstream point of the electron transfer interface in the flow direction of the sample fluid.
16. A measuring instrument comprising: a channel for moving a sample liquid containing a solid component and for providing a liquid reaction field, and first and second electrodes which are used to apply voltage to the liquid reaction field, wherein the first electrode comprises an electron transfer interface for providing electrons to the liquid reaction field or receiving electrons from the reaction field when voltage is applied to the liquid reaction field via the first and second electrodes, the measuring instrument comprising concentration means for increasing the concentration of the solid component in a part which contacts the electron transfer interface in the liquid reaction field; wherein the concentration means comprises a water-absorbing layer containing an absorbent polymer material; and wherein the absorbent polymer material has a water absorption power of 10 to 500 g/g.
The water-absorbing layer can also be placed downstream in the flow of sample liquid from the electron transfer interface in the channel. This water-absorbing layer is placed for example on either the substrate or the cover. In this case the dimension of the water-absorbing layer in the direction of flow of the sample liquid is preferably ¼ to ½ of the distance from the channel inlet to the furthest downstream point of the electron transfer interface in the direction of flow of the sample liquid so that the solid component can be concentrated as intended. For the same reasons it is desirable that during water absorption the thickness of the part having the formed water-absorbing layer be 0 to 15 μm.
Working electrode 31 and counter electrode 32 are formed extending in the long direction of substrate 3 on upper surface 30 of substrate 3. Reagent site 33 is also provided on upper surface 30 of substrate 3 so as to successively transect both working electrode 31 and counter electrode 32. The part of working electrode 31 which contacts reagent site 33 comprises electron transfer interface 31a.
Reagent site 33 is formed as a solid which comprises an oxidoreductase and an electron transporter. Glucose oxidase or glucose dehydrogenase for example can be used as the oxidoreductase. The electron transporter is oxidized or reduced by application of voltage and reactions, and in blood sugar measurement potassium ferricyanide for example is used as the electron transporter. In this embodiment, the electron transporter is included in its oxidized form before the blood is supplied.
As shown in FIGS. 2 and 3, water-absorbing layer 51 is formed on one side 50 of cover 5. This water-absorbing layer 51 is formed on one side 50 of cover 5 so as to face electron transfer interface 31a, which is located in internal channel 60 on working electrode 31. This water-absorbing layer 51 can be formed by affixing a water-absorbing sheet comprising an absorbent polymer material to cover 5. This water-absorbing layer 51 is formed so that its thickness is for example 1/30 to 1/10 of the height (H) of internal channel 60 without water absorption, and so that its thickness with water absorption is ⅕ to ⅗ the height (H) of internal channel 60.
As shown in FIG. 5, concentration measuring system 2 includes first and second terminals 20a and 20b, voltage applying part 21, current measuring part 22, detection part 23, control part 24, computation part 25 and display part 26.
First and second terminals 20a and 20b are provided for contact with terminals 31b and 32b of working electrode 31 and counter electrode 32 in biosensor 1 when biosensor 1 is mounted on concentration measuring system 2.
Voltage applying part 21 is for applying a voltage between working electrode 31 and counter electrode 32 of biosensor 1 via first and second terminals 20a and 20b. Voltage applying part 21 is electrically connected to first and second terminals 20a and 20b. Voltage applying part 21 includes for example a direct current power source such as a dry battery or charger.
Current measuring part 22 measures the current when a voltage is applied by means of voltage applying part 21 between terminals 31b and 32b of working electrode 31 and counter electrode 32.
As clearly shown in FIG. 5, biosensor 1 is first set on concentration measuring system 2. Terminals 31b and 32b of working electrode 31 and counter electrode 32 of biosensor 1 are thus connected to first and second terminals 20a and 20b of concentration measuring system 2. This allows voltage to be applied between working electrode 31 and counter electrode 32 via first and second terminals 20a and 20b. Under actual measurement conditions, a constant voltage is applied between working electrode 31 and counter electrode 32 as soon as biosensor 1 is mounted on concentration measuring system 2. The constant voltage applied between working electrode 31 and counter electrode 32 is set for example in the range of 100 to 1000 mV. In this embodiment, application of the constant voltage between working electrode 31 and counter electrode 32 is performed continuously until the response current for computing the blood sugar concentration has been measured.
Next, blood is supplied via end opening 61 of biosensor 1. As shown in FIGS. 4A and 4B, blood BL travels by capillary action through internal channel 60 from end opening 61 to end opening 62 of capillary 6. As clearly shown in FIG. 4B, blood BL is introduced until blood BL reaches end opening 62 and internal channel 60 of capillary 6 is full of blood BL. In this process reagent site 33 (see FIG. 4A) is dissolved by blood BL and a liquid reaction system is formed in internal channel 60. At this time water-absorbing layer 51 absorbs the plasma component of blood BL, and water-absorbing layer 51 grows in thickness. In this way, the movement of blood cells B1 is impeded by water-absorbing layer 51, and the concentration of blood cells B1 rises on and around the surface of electron transfer interface 31a of working electrode 31.
Within the liquid reaction system, the glucose in blood BL is oxidized by oxidoreductase while the electron transporter becomes reduced. When a voltage is applied, the reduced electron transporter moves to the surface of electron transfer interface 31a of working electrode 31, supplies electrons to electron transfer interface 31a and reverts to an oxidized electron transporter. The amount of electrons supplied to electron transfer interface 31a is measured as a response current by current measuring part 22 via first and second terminals 20a and 20b.
Meanwhile, the response current measured by current measuring part 22 is monitored by detection part 23, and once the response current exceeds a threshold detection part 23 detects that the blood has been supplied to reagent part 33 and reagent part 33 has dissolved. When detection part 23 has detected that the blood has been supplied, detection part 23 then evaluates whether a fixed time has passed since this detection.
In this embodiment, when blood BL is supplied to internal channel 60 of capillary 6 the plasma component of blood BL is absorbed by water-absorbing layer 51, increasing the concentration of blood cells B1 on and around the surface of electron transfer interface 31a of working electrode 31. In this way, the area on and around the surface of electron transfer interface 31a is artificially in the same state as if high-hematocrit blood BL were being supplied. Moreover, if an absorbent polymer material with a water absorption power of 10 to 500 g/g is used, water-absorbing layer 51 will absorb more plasma the lower the hematocrit value of blood BL. As a result, a similar high hematocrit state can be achieved around water-absorbing layer 51 regardless of whether the hematocrit value is high or low.
In the biosensor 1C shown in FIG. 8A, water-absorbing layer 51C is formed on substrate 3 downstream in the direction of blood flow from electron transfer interface 31a of working electrode 31. However, water-absorbing layer 51C may also be formed on cover 5.
In this biosensor 1C, as shown in FIG. 8B, when blood BL is introduced into capillary 6 water-absorbing layer 51C expands, decreasing the spatial cross-sectional area of the part of capillary 6 having formed water-absorbing layer 51C. As a result, the movement of blood cells B1 is impeded by water-absorbing layer 51C, blood cells B1 accumulate near electron transfer interface 31a and the concentration of blood cells B1 increases around electron transfer interface 31a.
In order for this to be effective, water-absorbing layer 51C is preferably formed so that the distance L between water-absorbing layer 51C and the upper surface of the capillary is 0 to 15 μm when capillary 6 is filled with blood. Moreover, in order to more reliably increase the concentration of blood cells B1 around electron transfer interface 31a it is desirable that dimension W1 of water-absorbing layer 51C in the direction of flow of blood BL be made relatively large. Dimension W1 in this case is preferably set to about ¼ to ½ of the distance W2 between inlet 68 of capillary 6 and downstream end 31a′ of electron transfer interface 31a.
A function similar to that of the water-absorbing layer 51C shown in FIGS. 8A and 8B can be achieved with a non-(or low-) water-soluble dam part. That is, rather than causing blood cells to accumulate due to absorption of the plasma component and expansion, the cross-sectional dimensions downstream from electron transfer interface 31a in capillary 6 can be made small by the formation of a dam before blood is supplied. This dam is preferably formed so that the distance (corresponding to L in FIG. 8B) between the dam and the substrate (or cover) is 5 to 15 μm. The dam can be formed on either the substrate or the cover.
In the biosensor 1D shown in FIG. 9, water-absorbing layer 51D is formed so as to have a part adjoining electron transfer interface 31a of working electrode 31. As shown in FIG. 10A, water-absorbing layer 51D may be arranged in two sites both upstream and downstream from electron transfer interface 31a (see FIG. 9), or as shown in FIG. 10B it can be formed as a rectangular frame. In the configuration shown in FIG. 10A, one of the two water-absorbing layers 51D may also be omitted.
In this example, a biosensor was formed with the same structure as in FIGS. 1 through 4. In this biosensor, the length L, width W and height H of internal channel 60 of capillary 6 were given as 3 mm, 1 mm and 40 μm, respectively (see FIGS. 1 and 3). Working electrode 31 and counter electrode 32 were formed by screen printing using carbon ink (Japan Acheson “Electrodag 423SS”). Reagent site 33 was given a two-layer structure consisting of an electron transport layer and an enzyme-containing layer. The electron transport layer was formed by first applying 0.4 μL of a first material liquid comprising an electron transporter to substrate 3, and then blow drying (30° C., 10% Rh) the first material liquid. The enzyme-containing layer was formed by first applying 0.3 μL of a second material liquid containing oxidoreductase to the electron transport layer, and then blow drying (30° C., 10% Rh) the second material liquid.
(1) SWN Solution (2) CHAPS Solution (3) Dis- (4) ACES Solution
Concen- Concen- tilled Concen-
tration Content tration Content water tration Content
Water-absorbing layer 51 was formed to a thickness of 2 μm by first applying 0.1 μL of a coating material comprising an absorbent polymer to the target site of cover 5 and then blow drying it (30° C., 10% Rh). 7 parts by weight of absorbent polymer (Sumitomo “Aquacork”) dissolved in 100 parts by weight of methanol was used as the coating material.
As can be seen from FIGS. 13 and 14, the biosensor of Example 1 had a bias of +5% in response current 5 seconds after initiation of blood supply within the range of Hct 20–69%, while the biosensor of Comparative Example 1 had a bias of ±20%. This means that in the biosensor of Example 1 Hct affects response current less than it does in the biosensor of Comparative Example 1. These results show that the effect of blood Hct is reduced by the inclusion of a water-absorbing layer 51 such as that of the biosensor in Example 1.
<- Previous Patent (Analysis method usin...) | Next Patent (Combustion pressure ...) ->