Redox probing for chemical information

A method for detecting the presence of an oxidative stress disorder from a signal signature comprising:

• contacting a sample with one or more redox-mediators defining a redox potential, wherein the sample is a biological sample derived from a subject at a point-of-care;
• providing an electrical input to the sample, the electrical input being a sequence having oxidative and reductive pulses including:
• a first input pulse defined by a first oxidative voltage greater than the redox potential and imposed for a first duration;
• a second input pulse defined by a second oxidative voltage equal to the first oxidative voltage and imposed for a second duration different than the first duration, the first input pulse and the second input pulse being separated by a first off voltage, the first off voltage being imposed for a duration greater than the first duration;
• and
• a third input pulse with a second off voltage between the second input pulse and the third input pulse, the third input pulse defined by a third oxidative voltage equal to the first oxidative voltage and a fourth oxidative voltage less than the third oxidative voltage, the third and fourth oxidative voltages bracketing the redox potential of the one or more redox mediators;
• measuring by electrodes a dynamic pattern of current and charge continuously over a period of time of the sample based on the one or more redox-mediators and the electrical input;
• measuring by an optical sensor an optical output continuously over the period of time of the sample based on the one or more redox-mediators and the electrical input;
• and
• using the dynamic pattern of current and charge and the optical output over the continuous period of time to derive a plurality of electrochemical or spectroelectrochemical pattern signal signatures for determining the presence of the oxidative stress disorder, thereby assaying for the presence of the oxidative stress disorder within the subject at the point-of-care.

A method of redox probing to access global chemical information on oxidative stress from a serum sample from a patient at a point-of-care, the method comprising:

• diluting the serum sample at the point-of-care with an iridium-based redox-mediator having a redox potential to define an assay with sensitivity to glutathione (GSH);
• providing a three pulse-redox-relaxation sequence electrical input to the diluted serum sample by dropping the diluted serum sample onto a screen-printed electrode system at the point-of-care;
• capturing at the point-of-care an optical signal and an electrical signal as a redox-state-dependent output response to the three pulse-redox-relaxation sequence electrical input in contact with the diluted serum sample, the three pulse-redox-relaxation sequence electrical input including:
• a first input pulse defined by a first on-voltage that is greater than the redox potential and imposed for a duration of one minute;
• a second input pulse defined by a second on-voltage that is greater than the redox potential and imposed for a duration of three minutes, the first and second input pulses separated by an off-voltage applied for a duration that allows the optical signal to decay;
• and
• a third input pulse defined by a third on-voltage that is greater than the redox potential and imposed for a duration of three minutes, and a fourth on-voltage that is less than the redox potential and imposed for a duration of three minutes;
• accessing the global chemical information on oxidative stress from the redox-state-dependent output response, the global chemical information being defined by a plurality of quantitative metrics relevant to oxidative stress, including:
• determining over the duration of each of the first input pulse, second input pulse and third input pulse each of (i) a charge transferred;
• (ii) an optical absorbance;
• and (iii) a cross-modal response defined as a slope between the optical signal and the electrical signal;
• determining a first-order rate constant for the decay of the optical signal over the duration of the off-voltage;
• and
• determining for the third input pulse a ratio of the charge transfer at the third on-voltage over the charge transfer at the fourth on-voltage.