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Cited by 158Analytical Chemistry and SensorsElectrochemical sensors and biosensorsAdvanced biosensing and bioanalysis techniques

The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index.

Extended gate field-effect-transistor for sensing cortisol stress hormone

Open access
Sheibani, Shokoofeh, Capua, Luca, Kamaei, Sadegh, Akbari, Sayedeh Shirin Afyouni, Zhang, Junrui, Guerin, Hoel, Ionescu, Adrian M.·2021·Communications Materials
DOI 10.1038/s43246-020-00114-xPMC PMC7815575
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Abstract

Cortisol is a hormone released in response to stress and is a major glucocorticoid produced by adrenal glands. Here, we report a wearable sensory electronic chip using label-free detection, based on a platinum/graphene aptamer extended gate field effect transistor (EG-FET) for the recognition of cortisol in biological buffers within the Debye screening length. The device shows promising experimental features for real-time monitoring of the circadian rhythm of cortisol in human sweat. We report a hysteresis-free EG-FET with a voltage sensitivity of the order of 14 mV/decade and current sensitivity up to 80% over the four decades of cortisol concentration. The detection limit is 0.2 nM over a wide range, between 1 nM and 10 µM, of cortisol concentrations in physiological fluid, with negligible drift over time and high selectivity. The dynamic range fully covers those in human sweat. We propose a comprehensive analysis and a unified, predictive analytical mapping of current sensitivity in all regimes of operation.

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Crossref · 10.1038/s43246-020-00114-x

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Figures

Fig. 1 Cortisol circadian rhythm and sensing principle of the extended-gate FET configuration for its measurement in a wearable patch. a Qualitative depiction of regular and irregular circadian levels of the cortisol produced by the adrenal glands in human body through the day, showing the need for high time granularity measurements to capture the pulsatile nature of cortisol, b concept of 3D-integrated cortisol sensor embedded in a patch used as wearable on the upper arm: at the bottom, the FET gate is extended through metal vias to a top metal layer covered with aptamer-decorated graphene. The system includes a top microfluidic channel that guides the sweat (LUT) over an integrated planar reference electrode and the functionalized graphene. c Schematic of extended-gate FET configuration used in this work: the functionalized electrode is electrically connected to the gate of the MOSFET transducer and immersed in the measurement solution while the extended-gate electrode is biased via the voltage applied on the reference electrode.
Fig. 1 Cortisol circadian rhythm and sensing principle of the extended-gate FET configuration for its measurement in a wearable patch. a Qualitative depiction of regular and irregular circadian levels of the cortisol produced by the adrenal glands in human body through the day, showing the need for high time granularity measurements to capture the pulsatile nature of cortisol, b concept of 3D-integrated cortisol sensor embedded in a patch used as wearable on the upper arm: at the bottom, the FET gate is extended through metal vias to a top metal layer covered with aptamer-decorated graphene. The system includes a top microfluidic channel that guides the sweat (LUT) over an integrated planar reference electrode and the functionalized graphene. c Schematic of extended-gate FET configuration used in this work: the functionalized electrode is electrically connected to the gate of the MOSFET transducer and immersed in the measurement solution while the extended-gate electrode is biased via the voltage applied on the reference electrode.CC BY · PubMed Central
Fig. 2 Functionalization steps of graphene electrode with aptamers and related experimental impedance and imaging. a Schematic of the process flow with successive functionalization steps of graphene electrode. b Depiction of the estimated nanoscale thicknesses of the functionalization layers. c EIS curves at different functionalization steps. d SEM image of the bare transferred graphene on top of the Pt electrode. e SEM image of the transferred graphene after functionalization with aptamers. As explained in the Supplementary Note 1, the aptamer sequence used in this work is 5′-amine-AG CAG CAC AGA GGT CAGATG CAA ACC ACA CCT GAG TGG TTAGCG TAT GTC ATT TAC GGACC-3′.
Fig. 2 Functionalization steps of graphene electrode with aptamers and related experimental impedance and imaging. a Schematic of the process flow with successive functionalization steps of graphene electrode. b Depiction of the estimated nanoscale thicknesses of the functionalization layers. c EIS curves at different functionalization steps. d SEM image of the bare transferred graphene on top of the Pt electrode. e SEM image of the transferred graphene after functionalization with aptamers. As explained in the Supplementary Note 1, the aptamer sequence used in this work is 5′-amine-AG CAG CAC AGA GGT CAGATG CAA ACC ACA CCT GAG TGG TTAGCG TAT GTC ATT TAC GGACC-3′.CC BY · PubMed Central
Fig. 3 AFM 3D morphology of the Pt electrode and XPS characterization. a After the graphene transfer, b after the PBSE linking, c after the aptamers functionalization. d–f Corresponding XPS graphs and fitting for different functionalization of the Pt electrode.
Fig. 3 AFM 3D morphology of the Pt electrode and XPS characterization. a After the graphene transfer, b after the PBSE linking, c after the aptamers functionalization. d–f Corresponding XPS graphs and fitting for different functionalization of the Pt electrode.CC BY · PubMed Central
Fig. 4 Experimental electrical validation of the proposed cortisol sensor and extracted sensitivities. a ID–VG transfer characteristics of cortisol sensor, in semi-logarithmic and linear scale for different cortisol concentrations. b Drift study and hysteresis. c Voltage sensitivity, SV, for different current levels in subthreshold and in linear working regime. d Experimental 3D mapping of extracted voltage sensitivity as a function of concentration and drain current (all range of experiments). e Comparison between the current sensitivity in the two working regimes, the solid symbols indicate the real data and the dashed lines indicate the expected current sensitivity based on calibrated modeling. f 3D mapping current sensitivity, SI, for different applied voltages (all operation range) and analyte concentration based on calibrated compact modeling using unified model of Eq. (2). g Predictive drain current model (solid line), based on Eq. (2), vs. cortisol concentration compared to data points (symbols) in weak (VREF = −0.2 V), moderate (VREF = 0.1 V) and strong inversion (VREF = 0.4 V). h Photo of the 0.18μm CMOS silicon chip designed and used in this work; the central pads are the top gate contacts of FET sensors.
Fig. 4 Experimental electrical validation of the proposed cortisol sensor and extracted sensitivities. a ID–VG transfer characteristics of cortisol sensor, in semi-logarithmic and linear scale for different cortisol concentrations. b Drift study and hysteresis. c Voltage sensitivity, SV, for different current levels in subthreshold and in linear working regime. d Experimental 3D mapping of extracted voltage sensitivity as a function of concentration and drain current (all range of experiments). e Comparison between the current sensitivity in the two working regimes, the solid symbols indicate the real data and the dashed lines indicate the expected current sensitivity based on calibrated modeling. f 3D mapping current sensitivity, SI, for different applied voltages (all operation range) and analyte concentration based on calibrated compact modeling using unified model of Eq. (2). g Predictive drain current model (solid line), based on Eq. (2), vs. cortisol concentration compared to data points (symbols) in weak (VREF = −0.2 V), moderate (VREF = 0.1 V) and strong inversion (VREF = 0.4 V). h Photo of the 0.18μm CMOS silicon chip designed and used in this work; the central pads are the top gate contacts of FET sensors.CC BY · PubMed Central

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Metadata

Authors
Sheibani, S., Capua, L., Kamaei, S., Akbari, S. S. A., Zhang, J., Guerin, H., & Ionescu, A. M.
Affiliations
  • University of Tehran (IR)
  • École Polytechnique Fédérale de Lausanne (CH)
Corresponding author
Ionescu, Adrian M.
ORCID
Venue
Communications Materials
Publisher
Springer Science and Business Media LLC
Published
2021-01-19
Volume
2
Issue
1
Pages
10-10
ISSN
2662-4443 (ISSN-L)
DOI
10.1038/s43246-020-00114-x
PMC
PMC7815575
OpenAlex
W3123066175
Cited by
158
References
61
Citations by year
2026: 17 · 2025: 30 · 2024: 40 · 2023: 28 · 2022: 28 · 2021: 15
FWCI
13.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Materials (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • H2020 European Research Council (695459)
Topics
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Chemistry and Sensors
  • Physical Sciences › Chemistry › Analytical Chemistry › Electrochemical sensors and biosensors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
Keywords
extended-gate field-effect transistor, wearable biosensors, label-free detection, human sweat, circadian rhythm, Debye screening, current sensitivity, detection limit

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