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Flexible nanoporous tunable electrical double layer biosensors for sweat diagnostics.

Munje RD, Muthukumar S, Panneer Selvam A, Prasad S - Sci Rep (2015)

Bottom Line: High sensitivity of detection of 1 pg/mL or 2.75 pmol cortisol in synthetic sweat and 1 ng/mL in human sweat is demonstrated with these novel biosensors.Specificity in synthetic sweat was demonstrated using a cytokine IL-1β.Cortisol detection in human sweat was demonstrated over a concentration range from 10-200 ng/mL.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Road, EC 39, Richardson, TX 75080.

ABSTRACT
An ultra-sensitive and highly specific electrical double layer (EDL) modulated biosensor, using nanoporous flexible substrates for wearable diagnostics is demonstrated with the detection of the stress biomarker cortisol in synthetic and human sweat. Zinc oxide thin film was used as active region in contact with the liquid i.e. synthetic and human sweat containing the biomolecules. Cortisol detection in sweat was accomplished by measuring and quantifying impedance changes due to modulation of the double layer capacitance within the electrical double layer through the application of a low orthogonally directed alternating current (AC) electric field. The EDL formed at the liquid-semiconductor interface was amplified in the presence of the nanoporous flexible substrate allowing for measuring the changes in the alternating current impedance signal due to the antibody-hormone interactions at diagnostically relevant concentrations. High sensitivity of detection of 1 pg/mL or 2.75 pmol cortisol in synthetic sweat and 1 ng/mL in human sweat is demonstrated with these novel biosensors. Specificity in synthetic sweat was demonstrated using a cytokine IL-1β. Cortisol detection in human sweat was demonstrated over a concentration range from 10-200 ng/mL.

No MeSH data available.


Sensor performance evaluation in human sweat using AC modulation through EIS.(a) Variation in imaginary impedance for cortisol concentration variation of 1 ng/mL to 200 ng/mL in human sweat. Inset shows the percent change in impedance. (b) Calibration dose response rationalization over the range of 1 ng/mL to 200 ng/mL. Inset shows test sample mapping using exponential fit.
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f6: Sensor performance evaluation in human sweat using AC modulation through EIS.(a) Variation in imaginary impedance for cortisol concentration variation of 1 ng/mL to 200 ng/mL in human sweat. Inset shows the percent change in impedance. (b) Calibration dose response rationalization over the range of 1 ng/mL to 200 ng/mL. Inset shows test sample mapping using exponential fit.

Mentions: We performed dose calibration experiments using human sweat for cortisol concentration of 1 ng/mL to 200 ng/mL. Since human sweat is a complex medium, we used higher concentration of 500 μg/mL of cortisol antibody (see Supplementary Fig. S2 online). The results shown in Fig. 6 are based on the Zimag measurements obtained at 100 Hz frequency for varying cortisol concentration in human sweat as we observed the highest SNR (signal-to-noise ratio) at this frequency. It can be observed from the inset of Fig. 6a that the percent change in impedance over the cortisol concentration in human sweat of 1 ng/mL to 200 ng/mL varies from 10% to 42%. The specific signal threshold is beyond 1 ng/mL concentration. Thus the limit of detection in human sweat is found to be at 1 ng/mL. However, the change in slope between 1 ng/mL to 10 ng/mL is not substantial. Thus we achieve LDR from 10 ng/mL to 200 ng/mL. As per the literature, cortisol concentration range in human sweat is reported ~8 ng/mL to 140 ng/mL3. The fractional change in dose Zimag impedance measurements with respect to the baseline Zimag impedance measurements for varying cortisol doses in human sweat is shown in Fig. 6b. This response was fitted using exponential fit and the correlation was found to be 0.9961. Figure 6b also shows the response for two test samples (human sweat with 50 ng/mL and 150 ng/mL cortisol dose concentrations respectively). The table inset in Fig. 6b compares the actual concentrations of cortisol tested to the measured values of cortisol concentration estimated from exponential fit. The measured values of cortisol estimated from the calibration dose response varied from the actual value of cortisol by an average of 12.5%, which is within the permissible limits of clinical standards as published by the Clinical And Laboratory Standards Institute22. Observed correlation between the measured and expected values of the test samples demonstrate analytical precision of the sensor. It can be concluded that the sensor performance is effective in clinically relevant range and the flexible sensor has demonstrated the potential for practical diagnostic applications.


Flexible nanoporous tunable electrical double layer biosensors for sweat diagnostics.

Munje RD, Muthukumar S, Panneer Selvam A, Prasad S - Sci Rep (2015)

Sensor performance evaluation in human sweat using AC modulation through EIS.(a) Variation in imaginary impedance for cortisol concentration variation of 1 ng/mL to 200 ng/mL in human sweat. Inset shows the percent change in impedance. (b) Calibration dose response rationalization over the range of 1 ng/mL to 200 ng/mL. Inset shows test sample mapping using exponential fit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588585&req=5

f6: Sensor performance evaluation in human sweat using AC modulation through EIS.(a) Variation in imaginary impedance for cortisol concentration variation of 1 ng/mL to 200 ng/mL in human sweat. Inset shows the percent change in impedance. (b) Calibration dose response rationalization over the range of 1 ng/mL to 200 ng/mL. Inset shows test sample mapping using exponential fit.
Mentions: We performed dose calibration experiments using human sweat for cortisol concentration of 1 ng/mL to 200 ng/mL. Since human sweat is a complex medium, we used higher concentration of 500 μg/mL of cortisol antibody (see Supplementary Fig. S2 online). The results shown in Fig. 6 are based on the Zimag measurements obtained at 100 Hz frequency for varying cortisol concentration in human sweat as we observed the highest SNR (signal-to-noise ratio) at this frequency. It can be observed from the inset of Fig. 6a that the percent change in impedance over the cortisol concentration in human sweat of 1 ng/mL to 200 ng/mL varies from 10% to 42%. The specific signal threshold is beyond 1 ng/mL concentration. Thus the limit of detection in human sweat is found to be at 1 ng/mL. However, the change in slope between 1 ng/mL to 10 ng/mL is not substantial. Thus we achieve LDR from 10 ng/mL to 200 ng/mL. As per the literature, cortisol concentration range in human sweat is reported ~8 ng/mL to 140 ng/mL3. The fractional change in dose Zimag impedance measurements with respect to the baseline Zimag impedance measurements for varying cortisol doses in human sweat is shown in Fig. 6b. This response was fitted using exponential fit and the correlation was found to be 0.9961. Figure 6b also shows the response for two test samples (human sweat with 50 ng/mL and 150 ng/mL cortisol dose concentrations respectively). The table inset in Fig. 6b compares the actual concentrations of cortisol tested to the measured values of cortisol concentration estimated from exponential fit. The measured values of cortisol estimated from the calibration dose response varied from the actual value of cortisol by an average of 12.5%, which is within the permissible limits of clinical standards as published by the Clinical And Laboratory Standards Institute22. Observed correlation between the measured and expected values of the test samples demonstrate analytical precision of the sensor. It can be concluded that the sensor performance is effective in clinically relevant range and the flexible sensor has demonstrated the potential for practical diagnostic applications.

Bottom Line: High sensitivity of detection of 1 pg/mL or 2.75 pmol cortisol in synthetic sweat and 1 ng/mL in human sweat is demonstrated with these novel biosensors.Specificity in synthetic sweat was demonstrated using a cytokine IL-1β.Cortisol detection in human sweat was demonstrated over a concentration range from 10-200 ng/mL.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Road, EC 39, Richardson, TX 75080.

ABSTRACT
An ultra-sensitive and highly specific electrical double layer (EDL) modulated biosensor, using nanoporous flexible substrates for wearable diagnostics is demonstrated with the detection of the stress biomarker cortisol in synthetic and human sweat. Zinc oxide thin film was used as active region in contact with the liquid i.e. synthetic and human sweat containing the biomolecules. Cortisol detection in sweat was accomplished by measuring and quantifying impedance changes due to modulation of the double layer capacitance within the electrical double layer through the application of a low orthogonally directed alternating current (AC) electric field. The EDL formed at the liquid-semiconductor interface was amplified in the presence of the nanoporous flexible substrate allowing for measuring the changes in the alternating current impedance signal due to the antibody-hormone interactions at diagnostically relevant concentrations. High sensitivity of detection of 1 pg/mL or 2.75 pmol cortisol in synthetic sweat and 1 ng/mL in human sweat is demonstrated with these novel biosensors. Specificity in synthetic sweat was demonstrated using a cytokine IL-1β. Cortisol detection in human sweat was demonstrated over a concentration range from 10-200 ng/mL.

No MeSH data available.