Electrochemical sensor and method for continuous analyte monitoring

A method for monitoring analyte concentration in a biological fluid by use of a sensor, the method comprising the steps of:

• providing a sensor comprising a volume of a hydrophilic medium for retaining an amount of analyte proportionate to the concentration of analyte in a biological fluid in contact with the sensor, an enclosure for said analyte retention volume, an electrode in contact with the hydrophilic medium, a redox enzyme in contact with the medium, and an electron transfer mediator for facilitating transfer of electrons between the enzyme and the electrode, the enzyme substantially not capable of transferring electrons to or from components of the biological fluid other than said analyte,
• contacting the biological fluid with the sensor and at initially predetermined intervals intermittently applying a potential to the electrode sufficient to oxidize the electron mediator and sensing current through said electrode as a function of the duration of the applied potential,
• maintaining the applied mediator oxidizing applied potential at least for a period of time sufficient to determine the rate of change of current with time through the electrode, and
• correlating the current flow with the current flow for known concentrations of said analyte in the retention medium,
• wherein the sensor additionally comprises at least a reference electrode and an auxiliary electrode and the method further comprises the steps of:
• intermittently establishing predetermined level of current to flow between said working electrode and said auxiliary electrode at initially predetermined intervals, and measuring the potential difference between said working electrode and the reference electrode to establish said level of current flow,
• maintaining said level of current flow at least for a period of time sufficient to determine the rate of change of potential necessary to maintain said current through said electrode with time, and
• correlating said potential with the potential for known concentrations of said analyte in the biological fluid.

A method for monitoring analyte concentration in a biological fluid by use of a sensor, the method comprising the steps of:

• providing a sensor comprising a volume of a hydrophilic medium for retaining an amount of analyte proportionate to the concentration of analyte in a biological fluid in contact with the sensor, an enclosure for said analyte retention volume, an electrode in contact with the hydrophilic medium, a redox enzyme in contact with the medium, and an electron transfer mediator for facilitating transfer of electrons between the enzyme and the electrode, the enzyme substantially not capable of transferring electrons to or from components of the biological fluid other than said analyte,
• contacting the biological fluid with the sensor and at initially predetermined intervals intermittently applying a potential to the electrode sufficient to oxidize the electron mediator and sensing current through said electrode as a function of the duration of the applied potential,
• retaining the redox enzyme and the mediator in the analyte retention volume by covalently bonding the mediator and the redox enzyme to the enclosure,
• maintaining the applied mediator oxidizing potential at least for a period of time sufficient to determine the rate of change of current with time through the electrode, and
• correlating the current flow with the current flow for known concentrations of said analyte in the retention medium.

A method for monitoring analyte concentration in a biological fluid, comprising:

• providing a sensor comprising a volume of a hydrophilic medium for retaining an amount of analyte in a biological fluid, an enclosure for said analyte retention volume, an electrode in contact with the hydrophilic medium, a redox enzyme in contact with the medium, and an electron transfer mediator for facilitating transfer of electrons between the enzyme and the electrode, the enzyme substantially not capable of transferring electrons to or from components of the biological fluid other than said analyte;
• contacting the biological fluid with the sensor and allowing an analyte of the biological fluid to diffuse into the analyte retention volume;
• varying the potential of the electrode over time from a mediator oxidizing potential sufficient to oxidize the electron mediator, to a potential at which no oxidation of the mediator occurs, to a reduction potential at which reduction of the mediator takes place;
• maintaining the mediator oxidizing applied potential at least for a period of time sufficient to determine the rate of change of current with time through the electrode;
• and
• sensing current through said electrode during application of the mediator oxidizing potential and correlating the sensed current with concentration of said analyte in the retention volume.

A method for monitoring analyte concentration in a biological fluid, comprising:

• providing a sensor comprising a volume of a hydrophilic medium for retaining an amount of analyte in a biological fluid, an enclosure for said analyte retention volume, an electrode in contact with the hydrophilic medium, a redox enzyme in contact with the medium, and a covalently bound electron transfer mediator that shifts between oxidized and reduced states for facilitating transfer of electrons between the enzyme and the electrode, the enzyme substantially not capable of transferring electrons to or from components of the biological fluid other than said analyte;
• contacting the biological fluid with the sensor and allowing an analyte of the biological fluid to diffuse into the analyte retention volume;
• applying in pulses of varying width a mediator oxidizing potential sufficient to oxidize the electron mediator to a potential at which no oxidation of the mediator occurs;
• maintaining the duration of the pulses of applied mediator oxidizing potential for a period of time sufficient to determine the rate of change of current with time through the electrode;
• and
• sensing current through said electrode during application of the mediator oxidizing potential and correlating the sensed current with concentration of said analyte in the retention volume.

A method for monitoring analyte concentration in a biological fluid, comprising:

• providing a sensor comprising a volume of a hydrophilic medium for retaining an amount of analyte in a biological fluid, an enclosure for said analyte retention volume, an electrode in contact with the hydrophilic medium, a redox enzyme in contact with the medium, and a covalently bound electron transfer mediator that shifts between oxidized and reduced states for facilitating transfer of electrons between the enzyme and the electrode;
• contacting the biological fluid with the sensor and allowing an analyte of the biological fluid to diffuse into the analyte retention volume;
• intermittently varying the potential of the electrode over time from a first potential at which no oxidation of the mediator takes place, to a second potential at which oxidation of the electron mediator takes place, to a third potential at which no oxidation of the mediator takes place;
• maintaining the second potential at least for a period of time sufficient to determine the rate of change of current with time through the electrode;
• and
• sensing current through said electrode during application of the second potential and correlating the sensed current with concentration of said analyte in the retention volume.