Biosensor and methods of use thereof
First Claim
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1. A sampling system for monitoring the concentration of an analyte present in a biological system, said sampling system comprising:
- (a) a reservoir containing an ionically conductive medium and 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 reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in the reservoir which reacts with the enzyme to produce hydrogen peroxide, wherein said sampling means is in operative contact with the reservoir; and
(c) a sensor element in operative contact with the reservoir, wherein said sensor element reacts electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal, and said sensor element comprises an electrode having a geometric surface area which ranges from about 0.1 to 3 cm2, a background current which ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity which 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
56 Claims
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1. A sampling system for monitoring the concentration of an analyte present in a biological system, said sampling system comprising:
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(a) a reservoir containing an ionically conductive medium and 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 reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in the reservoir which reacts with the enzyme to produce hydrogen peroxide, wherein said sampling means is in operative contact with the reservoir; and
(c) a sensor element in operative contact with the reservoir, wherein said sensor element reacts electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal, and said sensor element comprises an electrode having a geometric surface area which ranges from about 0.1 to 3 cm2, a background current which ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity which 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, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A sampling system for monitoring the concentration of an analyte present in a biological system, said sampling system comprising:
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(a) first and second reservoirs where each reservoir contains an ionically conductive medium and at least one reservoir further contains 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 reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in the reservoir which reacts with the enzyme to produce hydrogen peroxide, wherein said sampling means is in operative contact with the reservoir and comprises first and second iontophoretic electrodes in contact with said first and second reservoirs, wherein each iontophoretic electrode has 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 reservoirs, wherein said sensor element reacts electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23)
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24. A method for monitoring the concentration 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 reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in said 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 which reacts electrochemically with the hydrogen peroxide to produce a detectable signal, wherein said sensor element comprises an electrode having a geometric. surface area which ranges from about 0.1 to 3 cm2, a background current which ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity which 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 of the analyte in the biological system; and
(f) performing steps (a)-(d) continually, and step (e) periodically to monitor the concentration of the analyte in the biological system. - View Dependent Claims (25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 46)
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37. A method for monitoring the concentration 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 reservoirs where each reservoir contains an ionically conductive medium and at least the first reservoir further contains 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 reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in the reservoir which reacts with the enzyme to produce hydrogen peroxide, wherein said sampling means comprises first and second iontophoretic electrodes in operative contact with said first and second reservoirs, wherein each iontophoretic electrode has 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 reservoirs, wherein each sensor element is capable of reacting electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal;
(b) extracting said analyte from the biological system into the first reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in the first 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 which 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 of the analyte in the biological system; and
(g) performing steps (b)-(e) continually, and step (f) periodically to monitor the concentration of the analyte in the biological system. - View Dependent Claims (38, 39, 40, 41, 42, 43, 44, 45, 47)
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48. A method for monitoring the concentration 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 reservoirs where each reservoir contains 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 reservoirs to obtain a sub-millimolar (sub-mM) concentration of the analyte in the reservoirs which reacts with the enzyme to produce hydrogen peroxide, wherein said sampling means comprises first and second iontophoretic electrodes in operative contact with said first and second reservoirs, wherein each iontophoretic electrode has 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 reservoirs, wherein each sensor element is capable of reacting electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal;
(b) extracting said analyte from the biological system into the first reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in the first 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 which 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 of the analyte in the biological system;
(g) extracting said analyte from the biological system into the second reservoir to obtain a sub-millimolar (sub-mM) concentration of the analyte in the second 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 which 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 of the analyte in the biological system; and
(1) continually performing (i) steps (b)-(e) alternating with (ii) steps (g)-(j), and periodically performing steps (f) and (k) to monitor the concentration of the analyte in the biological system. - View Dependent Claims (49, 50, 51, 52, 53, 54)
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55. The sampling system of 1, wherein said biological system has a skin surface, and said extracting of analyte from the biological system into a reservoir further comprises enhancement of skin permeability by pricking with micro-needles.
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56. The sampling system of 15, wherein said biological system has a skin surface, and said extracting of analyte from the biological system into a reservoir further comprises enhancement of skin permeability by pricking with micro-needles.
Specification