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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 synthetic sweat using DC modulation.(a) Change in transverse current for varying orthogonal voltage at constant transverse voltage of 0.1 V for each immunoassay. (b) Change in transverse current for varying transverse voltage at constant 0 V orthogonal voltage for each immunoassay step. Inset shows transverse current-voltage output curve with applied transverse voltage from 0 V to 3 V and 3 V to 0 V for each immunoassay step. (c) Transverse current values under orthogonal voltage for each step of immunoassay for constant transverse voltage at 0.1 V and 0.5 V. (d) Change in the slope for every immunoassay step calculated from Fig. 4b.
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f4: Sensor performance evaluation in synthetic sweat using DC modulation.(a) Change in transverse current for varying orthogonal voltage at constant transverse voltage of 0.1 V for each immunoassay. (b) Change in transverse current for varying transverse voltage at constant 0 V orthogonal voltage for each immunoassay step. Inset shows transverse current-voltage output curve with applied transverse voltage from 0 V to 3 V and 3 V to 0 V for each immunoassay step. (c) Transverse current values under orthogonal voltage for each step of immunoassay for constant transverse voltage at 0.1 V and 0.5 V. (d) Change in the slope for every immunoassay step calculated from Fig. 4b.

Mentions: DC measurements included measuring standard transfer characteristics of three electrode sensor system. Changes in transverse current were observed by varying orthogonal and transverse voltages, one at a time while the other voltage was kept constant. Five sensors fabricated separately on nanoporous substrates were tested for the consistency in performance using cortisol. Figure 4a shows change in transverse current as orthogonal voltage is varied from −1 V to 1 V for different bio-immunoassay steps. These measurements are taken at a constant transverse voltage of 0.1 V. The variation of current from 4.1 mA to 2.5 mA due to different cortisol concentrations of 1 pg/ml to 100 ng/mL is observed. It is evident from Fig. 4a that baseline was differing by less than 0.5 mA over the range of 1 pg/mL and 100 pg/mL cortisol concentrations. The higher concentrations showed less than 2 mA deviation from the baseline current response. Figure 4b shows the transverse current vs. transverse voltage characteristic for different steps of the bio-immunoassay. These measurements were taken at a constant orthogonal voltage of 0.1 V. The Fig. 4d shows the slopes of the transfer characteristic calculated at each immunoassay step (ΔI/ΔV) in transverse direction. This indicates change in conductance between two electrodes as different biomolecules are functionalized on ZnO surface. It was observed that the slopes of the graphs varied from 19.1 to 8.7. The slopes at 1 pg/mL and 100 pg/mL concentration were 12.8 and 12.7 respectively very close to the slope of baseline measurement of 13. The antibody-hormone EDL formation is not being detected by DC measurement as the DC voltage applied is at a constant frequency and therefore is unable to read into the charge modulation occurring due to bioconjugation in EDL. The range of change in slope in Fig. 4d for 1 pg/mL to 100 ng/mL was 12.8 (2%) to 8.7 (33%) wrt baseline, where the baseline measurement was almost overlapping with output curves of lower concentrations 1 pg/mL and 100 pg/mL. The specific signal threshold was at 9.7 (25.4%) and the limit of detection was at 100 ng/mL.


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 synthetic sweat using DC modulation.(a) Change in transverse current for varying orthogonal voltage at constant transverse voltage of 0.1 V for each immunoassay. (b) Change in transverse current for varying transverse voltage at constant 0 V orthogonal voltage for each immunoassay step. Inset shows transverse current-voltage output curve with applied transverse voltage from 0 V to 3 V and 3 V to 0 V for each immunoassay step. (c) Transverse current values under orthogonal voltage for each step of immunoassay for constant transverse voltage at 0.1 V and 0.5 V. (d) Change in the slope for every immunoassay step calculated from Fig. 4b.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Sensor performance evaluation in synthetic sweat using DC modulation.(a) Change in transverse current for varying orthogonal voltage at constant transverse voltage of 0.1 V for each immunoassay. (b) Change in transverse current for varying transverse voltage at constant 0 V orthogonal voltage for each immunoassay step. Inset shows transverse current-voltage output curve with applied transverse voltage from 0 V to 3 V and 3 V to 0 V for each immunoassay step. (c) Transverse current values under orthogonal voltage for each step of immunoassay for constant transverse voltage at 0.1 V and 0.5 V. (d) Change in the slope for every immunoassay step calculated from Fig. 4b.
Mentions: DC measurements included measuring standard transfer characteristics of three electrode sensor system. Changes in transverse current were observed by varying orthogonal and transverse voltages, one at a time while the other voltage was kept constant. Five sensors fabricated separately on nanoporous substrates were tested for the consistency in performance using cortisol. Figure 4a shows change in transverse current as orthogonal voltage is varied from −1 V to 1 V for different bio-immunoassay steps. These measurements are taken at a constant transverse voltage of 0.1 V. The variation of current from 4.1 mA to 2.5 mA due to different cortisol concentrations of 1 pg/ml to 100 ng/mL is observed. It is evident from Fig. 4a that baseline was differing by less than 0.5 mA over the range of 1 pg/mL and 100 pg/mL cortisol concentrations. The higher concentrations showed less than 2 mA deviation from the baseline current response. Figure 4b shows the transverse current vs. transverse voltage characteristic for different steps of the bio-immunoassay. These measurements were taken at a constant orthogonal voltage of 0.1 V. The Fig. 4d shows the slopes of the transfer characteristic calculated at each immunoassay step (ΔI/ΔV) in transverse direction. This indicates change in conductance between two electrodes as different biomolecules are functionalized on ZnO surface. It was observed that the slopes of the graphs varied from 19.1 to 8.7. The slopes at 1 pg/mL and 100 pg/mL concentration were 12.8 and 12.7 respectively very close to the slope of baseline measurement of 13. The antibody-hormone EDL formation is not being detected by DC measurement as the DC voltage applied is at a constant frequency and therefore is unable to read into the charge modulation occurring due to bioconjugation in EDL. The range of change in slope in Fig. 4d for 1 pg/mL to 100 ng/mL was 12.8 (2%) to 8.7 (33%) wrt baseline, where the baseline measurement was almost overlapping with output curves of lower concentrations 1 pg/mL and 100 pg/mL. The specific signal threshold was at 9.7 (25.4%) and the limit of detection was at 100 ng/mL.

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.