Biosensors with porous chromatographic membranes
First Claim
1. A biosensor with porous membranes, comprising:
- (a) a lower substrate;
(b) an electrode layer patterned on the lower substrate;
(c) a porous membrane formed on a portion of the electrode layer, defining an area for an at least one electrode;
(d) an adhesive formed over a portion of the electrode layer not having the porous membrane, serving as an insulator;
(e) an upper substrate having a hole, the upper substrate facing with the porous membrane; and
(f) a second upper substrate containing a sample inlet for introducing samples through the hole to the biosensor, wherein either the at least one electrode or the porous membrane has an oxidase enzyme and an electron transfer mediator immobilized thereto, when a whole blood sample is introduced to the biosensor, the whole blood sample is separated into its components during the chromatographic motion through the porous membrane so that only blood plasma can be contacted with the electrode system.
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Accused Products
Abstract
Disclosed is a porous membrane built-in biosensor comprising (a) at least one substrate; (b) an electrode layer patterned on the substrate, consisting of an electrode system and a circuit connector; (c) an insulator, formed on parts of the electrode layer, for electrically separating the electrode system from a circuit connector; and (d) a porous membrane via the insulator on the electrode system, wherein, when a whole blood sample is introduced to the biosensor, the whole blood sample is separated into its components during the chromatographic motion through the porous membrane so that only blood plasma can be contacted with the electrode system. The porous membrane built-in biosensor is provided with a sample inlet, which allows samples to be introduced in a constant quantity to the biosensors porous membranes without pretreatment.
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Citations
27 Claims
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1. A biosensor with porous membranes, comprising:
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(a) a lower substrate;
(b) an electrode layer patterned on the lower substrate;
(c) a porous membrane formed on a portion of the electrode layer, defining an area for an at least one electrode;
(d) an adhesive formed over a portion of the electrode layer not having the porous membrane, serving as an insulator;
(e) an upper substrate having a hole, the upper substrate facing with the porous membrane; and
(f) a second upper substrate containing a sample inlet for introducing samples through the hole to the biosensor, wherein either the at least one electrode or the porous membrane has an oxidase enzyme and an electron transfer mediator immobilized thereto, when a whole blood sample is introduced to the biosensor, the whole blood sample is separated into its components during the chromatographic motion through the porous membrane so that only blood plasma can be contacted with the electrode system. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
(a) the lower substrate 10;
(b) the electrode layer formed on the lower substrate 10, comprising a J-shaped working electrode connector strip 11′
with a working electrode 11 established thereon, a counter electrode connector strip 12′
, and a reference electrode connector strip 13′
with a reference electrode 13 established thereon;
(c) the porous membrane 16 or the working electrode 11 having the oxidase enzyme and the electron transfer mediator immobilized thereto;
(d) the adhesive 17 covered over a portion of the lower substrate 10 not having the porous membrane 16;
(e) a Y-shaped circuit connector strip 20 with a counter electrode 12 on the branched line ends, and (f) the upper substrate 10′
, fixed by the adhesive 17, having the hole 18; and
(g) the second upper substrate 10″
, fixed to the first upper substrate 10′
via an adhesive 17, having the sample inlet 14, wherein the sample inlet has two opposite open ends through which samples are introduced to the biosensor.
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3. The biosensor as set forth in claim 1, wherein said biosensor is a face-to-face type with a three-electrode system, comprising:
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(a) the lower substrate 10;
(b) the electrode layer formed on the lower substrate 10, comprising a J-shaped working electrode connector strip 11′
with a working electrode 11 established thereon, a counter electrode connector strip 12′
, and a reference electrode connector strip 13′
with a reference electrode 13 established thereon;
(c) the porous membrane 16 or the working electrode 11 having the oxidase enzyme and the electron transfer mediator immobilized thereto;
(d) the adhesive 17 covered over a portion of the lower substrate 10 not having porous membrane 16;
(e) a Y-shaped circuit connector strip 20 with a counter electrode 12 on the branched line ends, and (f) the upper substrate 10′
, via the adhesive 17, having the hole 18; and
(g) the second upper substrate 10″
with a second hole 18′
fixed to the first upper substrate 10′
via an adhesive 17, having the sample inlet 14 extending from a mid point to an end of the second upper substrate 10″
, wherein the sample inlet has one open end through which samples are introduced to the biosensor.
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4. The biosensor as set forth in claim 1, wherein said biosensor is a face-to-face type employing a two-electrode system, comprising:
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(a) the lower substrate 10;
(b) the electrode layer formed on the lower substrate 10, comprising a Y-shaped working electrode connector strip 11′
with a working electrode 11 established thereon and a counter electrode connector strip 12′
the latter it is connected to one end portion of a circuit connector strip 20 on the upper substrate 10′
;
(c) the porous membrane 16 or the working electrode 11 having the oxidase enzyme and the electron transfer mediator immobilized thereto;
(d) the adhesive 17 covered over a portion of the lower substrate 10 not having the porous membrane 16;
(e) the Y-shaped circuit connector strip 20 with a counter electrode 12 on the branched line ends, and (f) the upper substrate 10′
, via the adhesive 17, having the hole 18; and
(g) the second upper substrate 10″
, having the sample inlet, fixed to the first upper substrate 10′
14 via an adhesive 17, wherein the sample inlet has two opposite open ends through which samples are introduced to the biosensor.
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5. The biosensor as set forth in claim 1, wherein said biosensor is a face-to-face type with a two-electrode system, comprising:
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(a) the lower substrate 10;
(b) the electrode layer formed on the lower substrate 10, comprising a Y-shaped working electrode connector strip 11′
with a working electrode 11 established thereon and a counter electrode connector strip 12′
established thereon;
(c) the porous membrane 16 or the working electrode 11 having the oxidase enzyme and the electron transfer mediator immobilized thereto;
(d) the adhesive 17 covered over a portion of the lower substrate 10 not having the porous membrane 16;
(e) a Y-shaped circuit connector strip 20 with a counter electrode 12 on the branched line ends, (f) the upper substrate 10′
, fixed by the adhesive 17, having the hole 18; and
(g) the second upper substrate 10″
with a second hole of upper substrate 18′
, having the sample inlet 14, fixed to the first upper substrate 10′
via an adhesive 17, wherein the sample inlet has one open end through which samples are introduced to the biosensor.
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6. The biosensor as set forth in claim 1, wherein said biosensor is a face-to-face type employing a two-electrode system, all of the electrodes being made of carbon ink only, comprising:
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(a) the lower substrate 10;
(b) the electrode layer formed on the lower substrate 10, comprising a Y-shaped working electrode connector strip 11′
with a working electrode 11 established thereon and a counter electrode connector strip 12′
;
(c) the porous membrane 16 or the working electrode 11 having the oxidase enzyme and the electron transfer mediator immobilized thereto;
(d) the adhesive 17 covered over a portion of the lower substrate 10 not having the porous membrane 16;
(e) a Y-shaped circuit connector strip 20 with a counter electrode 12 on the branched line ends, (f) the upper substrate 10′
, formed on the adhesive 17, having the hole 18; and
(g) the second upper substrate 10″
, having the sample inlet 14, fixed to the first upper substrate 10′
via an adhesive 17, wherein the sample inlet has two opposite open ends through which samples are introduced to the biosensor.
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7. The biosensor as set forth in claim 1, wherein said biosensor is a face-to-face type with a three-electrode system characterized by providing a circular space for a sample inlet, comprising:
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(a) the lower substrate 10;
(b) the electrode layer formed on the lower substrate 10, comprising a J-shaped working electrode connector strip 11′
with a working electrode 11 established thereon, a counter electrode connector strip 12′
, and a reference electrode connector strip 13′
with a reference electrode 13 established thereon;
(c) the porous membrane 16 or the working electrode 11 having the oxidase enzyme and the electron transfer mediator immobilized thereto;
(d) the adhesive 17 covered over a portion of the lower substrate 10 not having the porous membrane 16;
(e) a Y-shaped circuit connector strip 20 with a counter electrode 12 on the branched line ends, (f) the upper substrate 10′
, fixed by the adhesive 17, having the hole 18 through which samples are introduced inside the biosensor; and
(g) a circular second upper substrate 10″
with a circular sample inlet 14, fixed to the upper substrate 10′
via an adhesive 17.
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8. The biosensor as set forth in claim 1, wherein said biosensor is a face-to-face type with a two-electrode system characterized by providing a circular space for a sample inlet, comprising:
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(a) the lower substrate 10;
(b) the electrode layer formed on the lower substrate 10, comprising a J-shaped working electrode connector strip 11′
with a working electrode 11 established thereon, a counter electrode connector strip 12′
, the latter it is connected to one end portion circuit connector strip 20 on the upper substrate 10′
;
(c) the porous membrane 16 or the working electrode 11 having the oxidase enzyme and the electron transfer mediator immobilized thereto;
(d) the adhesive 17 covered over a portion of the lower substrate 10 not having the porous membrane 16;
(e) the Y-shaped circuit connector strip 20 with a counter electrode 12 on the branched line ends, (f) the upper substrate 10′
, fixed by the adhesive 17, having the hole 18 through which samples are introduced inside the biosensor; and
(g) a circular second upper substrate 10″
with a circular sample inlet 14, fixed to the upper substrate 10′
via an adhesive 17.
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9. The biosensor as set forth in claim 1, wherein said biosensor is a flat type adopting a three-electrode system, comprising:
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(a) the lower substrate 10;
(b) the electrode layer, formed on the lower substrate 10, comprising a working electrode connector strip 11′
with a working electrode 11 established thereon, a counter electrode connector strip 12′
with a J-shaped counter electrode 12 established thereon, and a reference electrode connector strip 13′
with a reference electrode 13 established thereon;
(c) the porous membrane 16, formed on a predetermined area of the electrode layer, covering the working electrode 11, and the adhesive 17 deposited over a portion of the lower substrate not having the porous membrane 16;
(d) the upper substrate 10′
with the hole 18 fixed to the lower substrate 10 via the adhesive 17; and
(e) the second upper substrate 10″
with a second hole 18′
, having the sample inlet, fixed to the first upper substrate 10′
14 via an adhesive 17, wherein said sample inlet 14 is formed straightly extending from a mid point to one end of the second upper substrate 10″ and
is introduced samples to the biosensor.
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10. The biosensor as set forth in claim 1, wherein said biosensor is a flat type employing a two-electrode system, comprising:
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(a) the lower substrate 10;
(b) the electrode layer, formed on the substrate 10, consisting of a working electrode connector strip 11′
with a working electrode 11 established thereon and a counter electrode connector strip 12′
with a J-shaped counter electrode 12 established thereon;
(c) the porous membrane 16, formed on a predetermined area of the electrode system, covering the working electrode 11, and an adhesive 17 deposited over a portion of the lower substrate not having the porous membrane 16;
(d) the upper substrate 10′
with the hole 18 fixed to the lower substrate 10 via the adhesive 17; and
(e) the second upper substrate 10″
with a second hole of 18′
, having the sample inlet 14, fixed to the first upper substrate 10′
via an adhesive 17, wherein said a sample inlet 14 is formed straightly extending from a mid point to one end of the second upper substrate 10″ and
is introduced samples to the biosensor.
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11. The biosensor as set forth in claim 1, wherein the porous membrane 16 contains pores ranging from 5 to 20 μ
- m in diameter.
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12. The biosensor as set forth in claim 1, wherein the porous membrane 16 is selected from paper, a hydrophilic organic polymer or a hygroscopic ceramic polymer.
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13. The biosensor as set forth in claim 12, wherein a hydrophilic organic polymer or a hygroscopic ceramic polymer is selected from the group consisting of nylon, hydrophilic polyester sulfone membranes, hydrophilic mixed cellulose esters, polytetrafluoroethylene membranes, polyvinylidine fluoride membranes, ion-selective membranes, glass fiber, and polyester fiber or its modified fiber membranes.
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14. The biosensor as set forth in claim 1, wherein the porous membrane 16 is selected from a group consisting of nitrocellulose paper, polyester fiber or its modified fiber membranes and filter paper.
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15. The biosensor as set forth in claim 1, wherein the oxidase is selected from the group consisting of glucose oxidase, lactate oxidase, cholesterol oxidase, glutamate oxidase, horse radish peroxidase and alcohol oxidase.
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16. The biosensor as set forth in claim 1, wherein the electron transfer mediator is selected from the group consisting of hexaamineruthenium (III) chloride, potassium ferricyanide, potassium ferrocyanide, dimethylferrocene (DMF), ferricinium, ferocene-monocarboxylic acid (FCOOH), 7,7,8,8-tetracyanoquinodimethane (TCNQ), tetrathiafulvalene (TTF), nickelocene (Nc), N-methylacidinium (NMA+), tetrathiatetracene (TTT, N-methylphenazinium (NMP+), hydroquinone, 3-dimethylaminobenzoic acid (MBTHDMAB), 3-methyl-2-benzothiozolinone hydrazone, 2-methoxy-4-allylphenol, 4-aminoantipyrine (AAP), dimethylaniline, 4-aminoantipyrene, 4-methoxynaphthol, 3,3′
- ,5,5′
-tetramethylbenzidine (TMB), 2,2-azino-di-[3-ethylbenzothizoline sulfonate], o-dianisidine, o-toluidine, 2,4-dichloro phenol, 4-aminophenazone, benzidine, prussian blue as mixed-valence compounds capable of forming redox couples.
- ,5,5′
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17. The biosensor as set forth in claim 1, wherein the substrate is formed of ceramic, plastic, silicon, alumina glass plates, or polymeric materials.
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18. The biosensor as set forth in claim 1, further comprising a protective membrane 22 is formed of an organic polymer selected from the group consisting of polyester, polyvinyl chloride, and polycarbonate.
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19. The biosensor as set forth in claim 1, wherein the at least one electrode is fabricated in a direct chemical vacuum deposition process or in a plasma deposition process.
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20. The biosensor as set forth in claim 1, wherein the sample inlet 14 is modified with a surfactant or by additives to improve the mobility of the whole blood sample through the porous membrane.
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21. The biosensor as set forth in claim 1, wherein the sample inlet 14 is modified in morphology and size by applying grooves to the sample inlet or the hole.
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22. The biosensor as set forth in claim 1, wherein the pretreatment layer 19 is provided with a sample inlet for removing various interfering materials, whereby the quantification of samples of interest can be improved in measurement convenience, accuracy and precision.
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23. A biosensor with porous membranes, wherein said biosensor is a differential face-to face type with a three-electrode system, comprising:
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(a) a lower substrate 10;
(b) a plurality of spaced first circuit connectors;
formed on the lower substrate 10,(c) a counter electrode 12 and a reference electrode 13, both being coated on the first circuit connectors 9 at predetermined regions;
(d) an insulator 15 covering the surface of the lower substrate 10 with the exception of a portion of the lower substrate containing the counter electrode 12 the reference electrode 13, and a terminal region of the lower substrate 10;
(e) a porous membrane 16 located on the counter electrode 12 and the reference electrode 13, the porous membrane 16 having the same dimension as the exposed portion of the counter electrode 12 and a reference electrode 13;
(f) an adhesive 17 deposited over the insulator 15 (g) a working electrode 11 atop the porous membrane 16;
(h) a second circuit connector 9′
extending to the working electrode 11;
(i) upper substrate 10′
covering second insulator 15′
that exposes the working electrode 11;
(j) a plurality of differential circuit connectors 90 formed below the lower substrate 10;
(k) a differential counter electrode 120 and a differential reference electrode 130;
(l) a differential insulator 150 formed on the differential circuit connectors 90;
(m) a differential porous membrane 160;
(n) a differential adhesive 170 below the differential insulator 150;
(o) a differential working electrode 110 on the differential porous membrane 160;
(p) a second differential circuit connector 90 with the differential adhesive 170;
(q) a differential second insulator 150; and
(r) a differential upper substrate 100, each of the differential elements of (i) through (r) functioning in the same manner as that of its corresponding elements of (a) through (j).
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24. A biosensor with porous membranes, wherein said biosensor is a differential face-to-face type with a two-electrode system, comprising:
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(a) a lower substrate 10;
(b) a plurality of spaced first circuit connectors 9;
formed on the lower substrate 10,(c) a counter electrode 12 being coated on the first circuit connectors 9 at a predetermined region;
(d) an insulator 15 covering the surface of the lower substrate 10 exception of a portion of the lower substrate containing the counter electrode 12 and a terminal region of the lower substrate 10;
(e) a porous membrane 16 located on the counter electrode 12, having the same dimension as the exposed portion containing the counter electrode;
(f) an adhesive 17 deposited over the insulator 15;
(g) a working electrode 11 atop the porous membrane 16;
(h) a second circuit connector 9′
extending to the working electrode 11;
(i) upper substrate 10′
covering a second insulator 15′
that exposes the working electrode 11;
(j) a plurality of differential circuit connectors 90 formed below the lower substrate 10;
(k) a differential counter electrode 120;
(l) a differential insulator 150 formed on the differential circuit connectors 90;
(m) a differential porous membrane 160;
(n) a differential adhesive 170 below the differential insulator 150;
(o) a differential working electrode 110 on the differential porous membrane 160;
(p) a second differential circuit connector 90 with the differential adhesive 170;
(q) a differential second insulator 150; and
(r) a differential upper substrate 100, each of the differential elements of (j) through (r) functioning in the same manner as that of its corresponding elements of (a) through (i).
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25. A biosensor with porous membranes, wherein said biosensor is a face-to-face type employing a two-electrode system, characterized in that the sample inlet 14 is formed in an upper substrate 10 not in a second upper substrate 10 and all electrodes are fabricated by carbon ink only, comprising:
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(a) a lower substrate 10;
(b) an electrode layer formed on the lower substrate 10, comprising a Y-shaped working electrode connector strip 11 with a working electrode 11 established thereon and a counter electrode connector strip 12, all of the electrodes coated with carbon ink only;
(c) a porous membrane 16, formed on a predetermined area of the electrode layer, covering the working electrode 11;
(d) an adhesive 17 covered over a portion of the lower substrate 10 not having the porous membrane 16;
(e) a Y-shaped circuit connector strip 20 with a counter electrode 12 coated with carbon ink only, (f) an upper substrate 10, fixed by the adhesive 17, having a sample inlet 14 extending in the lengthwise direction to one end of the upper substrate 10 from a mid point and thus having an open end; and
(g) a second upper substrate 10, fixed to the first upper substrate 10 via an adhesive 17, having a second hole of upper substrate 18.
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26. A biosensor with porous membranes, wherein said biosensor is a flat type employing a three-electrode system, which has a porous membrane as a lower substrate, comprising:
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(a) a lower substrate made of a porous membrane 16;
(b) an insulator 15 formed on one half portion of the lower substrate 16, an electrode system, formed on the insulator 15, comprising a working electrode connector strip 11 with a working electrode 11 established thereon, a counter electrode connector strip 12 with a counter electrode 12 established thereon, and a reference electrode connector strip 13 with a reference electrode 13 established thereon, and a pretreatment layer 19 adjacent to the insulator 15; and
(c) an upper substrate 10 fixed onto the another half portion of the porous membrane 16 via an adhesive 17, having an sample inlet 14 which is formed in the direction traversing the electrode system and has two open ends, wherein through the sample inlet having two open ends, samples can be introduced from both the left and right ends of the biosensor adopting the three-electrode system.
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27. A biosensor with porous membranes, wherein said biosensor is a flat type employing a two-electrode system, which has a porous membrane as a lower substrate, comprising:
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(a) a lower substrate made of a porous membrane 16;
(b) an insulator 15 formed on one half portion of the lower substrate 16, an electrode system, formed on the insulator 15, comprising a working electrode connector strip 11 with a working electrode 11 established thereon and a counter electrode connector strip 12 with a counter electrode 12 established thereon and a pretreatment layer 19 adjacent to the insulator 15; and
(c) an upper substrate 10 fixed onto the another half portion of the porous membrane 16 via an adhesive 17, having an sample inlet 14 which is formed in the direction traversing the electrode system and has two open ends, wherein through the sample inlet having two open ends, samples can be introduced from both the left and right ends of the biosensor adopting the three-electrode system.
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Specification