Biosensor, iontophoretic sampling system, and methods of use thereof
First Claim
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1. A sampling system for monitoring the concentration or amount of an analyte present in a biological system, said sampling system comprising:
- (a) a collection reservoir comprising an enzyme capable of reacting with the analyte to produce hydrogen peroxide;
(b) sampling means for extracting the analyte from the biological system into the collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the collection reservoir, wherein said sampling means is in operative contact with the collection reservoir; and
(c) a sensor element in operative contact with the collection reservoir, said sensor element comprising an electrode, wherein said electrode reacts electrochemically with the hydrogen peroxide produced in the collection reservoir to provide a detectable signal, said electrode comprising a geometric surface area that ranges from about 0.1 to 3 cm2, a background current that ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity that ranges from about 6 to 180 nA/μ
M of hydrogen peroxide when measured in a buffer solution at 0.6V.
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Abstract
An automated system for continual transdermal extraction of analytes present in a biological system is provided. The system can be used for detecting and/or measuring the concentration of the analyte using an electrochemical biosensor detection means. The system optionally uses reverse iontophoresis to carry out the continual transdermal extraction of the analytes.
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Citations
63 Claims
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1. A sampling system for monitoring the concentration or amount of an analyte present in a biological system, said sampling system comprising:
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(a) a collection reservoir comprising an enzyme capable of reacting with the analyte to produce hydrogen peroxide;
(b) sampling means for extracting the analyte from the biological system into the collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the collection reservoir, wherein said sampling means is in operative contact with the collection reservoir; and
(c) a sensor element in operative contact with the collection reservoir, said sensor element comprising an electrode, wherein said electrode reacts electrochemically with the hydrogen peroxide produced in the collection reservoir to provide a detectable signal, said electrode comprising a geometric surface area that ranges from about 0.1 to 3 cm2, a background current that ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity that ranges from about 6 to 180 nA/μ
M of hydrogen peroxide when measured in a buffer solution at 0.6V.- View Dependent Claims (2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19)
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7. The sampling system of claim 7, wherein the iontophoretic electrode is a bimodal electrode that is also able to act as a counter electrode, and wherein the sensor element comprises a sensing electrode and a reference electrode.
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18. The sampling system of 1, wherein (i) said biological system comprises a skin surface, and (ii) said sampling system further comprises a skin permeability enhancer, said skin permeability enhancer comprising micro-needles.
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20. A sampling system for monitoring the concentration or amount of an analyte present in a biological system, said sampling system comprising:
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(a) first and second collection reservoirs, wherein each collection reservoir comprises an ionically conductive medium and at least one collection reservoir further comprises an enzyme capable of reacting with the analyte to produce hydrogen peroxide;
(b) reverse iontophoretic sampling means for extracting the analyte from the biological system into the collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the collection reservoir, wherein said sampling means is in operative contact with the collection reservoir and comprises first and second iontophoretic electrodes in contact with said first and second collection reservoirs, wherein each iontophoretic electrode comprises a geometric area ranging from about 0.3 to 1.0 cm2 , and is capable of repeated cycles of current passage in the range of about 0.01 to 1.0 mA/cm2 of electrode area; and
(c) first and second sensor elements in operative contact with the first and second collection reservoirs, wherein each sensor element comprises an electrode that reacts electrochemically with the hydrogen peroxide produced in the collection reservoir to provide a detectable signal, each electrode comprising a geometric surface area that ranges from about 0.1 to 3 cm2 , a background current that ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity that ranges from about 6 to 180 nA/μ
M of hydrogen peroxide when measured in a buffer solution at 0.6V.- View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28)
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29. The sampling system of 20, wherein (i) said biological system comprises a skin surface, and (ii) said sampling system further comprises a skin permeability enhancer, said skin permeability enhancer comprising micro-needles.
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30. A method for monitoring the concentration or amount of an analyte present in a biological system, said method comprising:
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(a) extracting said analyte from the biological system into a collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in said collection reservoir;
(b) contacting the analyte extracted in step (a) with an enzyme that reacts with the analyte to produce hydrogen peroxide;
(c) detecting the hydrogen peroxide produced in step (b) with a sensor element comprising an electrode that reacts electrochemically with the hydrogen peroxide to produce a detectable signal, said electrode comprising a geometric surface area that ranges from about 0.1 to 3 cm2, a background current that ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity that ranges from about 6 to 180 nA/μ
M of hydrogen peroxide when measured in a buffer solution at 0.6V;
(d) measuring the signal produced in step (c);
(e) correlating the measurement obtained in step (d) with the concentration or amount of the analyte in the biological system; and
(f) performing repeated cycles of steps (a)-(e) over a time period to monitor the concentration or amount of the analyte in the biological system. - View Dependent Claims (31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46)
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47. A method for monitoring the concentration or amount of an analyte present in a biological system, said method comprising:
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(a) contacting a sampling system with the biological system, said sampling system comprising (i) first and second collection reservoirs, wherein each collection reservoir comprises an ionically conductive medium and at least the first collection reservoir further comprises an enzyme capable of reacting with the analyte to produce hydrogen peroxide;
(ii) reverse iontophoretic sampling means for extracting the analyte from the biological system into the first collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the collection reservoir, wherein said sampling means comprises first and second iontophoretic electrodes in operative contact with said first and second collection reservoirs, wherein each iontophoretic electrode comprises a geometric area ranging from about 0.3 to 1.0 cm2, and is capable of repeated cycles of current passage in the range of about 0.01 to 1.0 mA/cm2 of electrode area; and
(iii) first and second sensor elements in operative contact with the first and second collection reservoirs, wherein each sensor element comprises an electrode capable of reacting electrochemically with the hydrogen peroxide produced in the collection reservoir to provide a detectable signal, each electrode comprising a geometric surface area that ranges from about 0.1 to 3 cm2, a background current that ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity that ranges from about 6 to 180 nA/μ
M of hydrogen peroxide when measured in a buffer solution at 0.6V;
(b) extracting said analyte from the biological system into the first collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the first collection reservoir, wherein said extracting is carried out using the reverse iontophoretic system;
(c) contacting the analyte extracted in step (b) with an enzyme that reacts with the analyte to produce hydrogen peroxide;
(d) detecting the hydrogen peroxide produced in step (c) with the first sensor element that reacts electrochemically with the hydrogen peroxide to produce a detectable signal;
(e) measuring the signal produced in step (d);
(f) correlating the measurement obtained in step (e) with the concentration or amount of the analyte in the biological system; and
(g) performing repeated cycles of steps (b)-(f) over a time period to monitor the concentration or amount of the analyte in the biological system. - View Dependent Claims (48, 49, 50, 51, 52, 53, 54, 55, 56)
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57. A method for monitoring the concentration or amount of an analyte present in a biological system, said method comprising:
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(a) contacting a sampling system with the biological system, said sampling system comprising (i) first and second collection reservoirs, wherein each collection reservoir comprises an ionically conductive medium and an enzyme capable of reacting with the analyte to produce hydrogen peroxide;
(ii) reverse iontophoretic sampling means for extracting the analyte from the biological system into the collection reservoirs to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the collection reservoirs, wherein said sampling means comprises first and second iontophoretic electrodes in operative contact with said first and second collection reservoirs, wherein each iontophoretic electrode comprises a geometric area ranging from about 0.3 to 1.0 cm2, and is capable of repeated cycles of current passage in the range of about 0.01 to 1.0 mA/cm2 of electrode area; and
(iii) first and second sensor elements in operative contact with the first and second collection reservoirs, wherein each sensor element comprises an electrode capable of reacting electrochemically with the hydrogen peroxide produced in the collection reservoir to provide a detectable signal, each electrode comprising a geometric surface area that ranges from about 0.1 to 3 cm2, a background current that ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity that ranges from about 6 to 180 nA/μ
M of hydrogen peroxide when measured in a buffer solution at 0.6V;
(b) extracting said analyte from the biological system into the first collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the first collection reservoir, wherein said extracting is carried out using the reverse iontophoretic system;
(c) contacting the analyte extracted in step (b) with an enzyme that reacts with the analyte to produce hydrogen peroxide;
(d) detecting the hydrogen peroxide produced in step (c) with the first sensor element that reacts electrochemically with the hydrogen peroxide to produce a detectable signal;
(e) measuring the signal produced in step (d);
(f) correlating the measurement obtained in step (e) with the concentration or amount of the analyte in the biological system;
(g) extracting said analyte from the biological system into the second collection reservoir to obtain a sub-millimolar (sub-mM) concentration or amount of the analyte in the second collection reservoir, wherein said extracting is carried out using the reverse iontophoretic system;
(h) contacting the analyte extracted in step (g) with an enzyme that reacts with the analyte to produce hydrogen peroxide;
(i) detecting the hydrogen peroxide produced in step (h) with the second sensor element that reacts electrochemically with the hydrogen peroxide to produce a detectable signal;
(j) measuring the signal produced in step (i);
(k) correlating the measurement obtained in step (j) with the concentration or amount of the analyte in the biological system; and
(l) performing repeated cycles of (i) steps (b)-(e) alternating with (ii) steps (g)-(j) over a time period, and periodically performing steps (f) and (k) over the time period to monitor the concentration or amount of the analyte in the biological system. - View Dependent Claims (58, 59, 60, 61, 62, 63)
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Specification