Nanosensor-Based Real-Time Monitoring of Stress Biomarkers in Human Saliva Using a Portable Measurement System
Abstract
Small molecules with no or little charge are considered to have minimal impact on signals measured by field effect transistor (FET) sensors. This fact typically excludes steroids from the family of analytes, detected by FETs. We present a portable multiplexed platform based on an array of nanowire sensors for label-free monitoring of daytime levels of the stress hormone cortisol in saliva samples, obtained from multiple donors. To achieve an effective quantification of the cortisol with FETs, we rely on the specific DNA aptamer sequences as receptors, bringing the complex "target-receptor" closer to the nanowire surface. Upon binding, cortisol induces conformational changes of negatively charged aptamers, wrapping it into a close proximity to the silicon nanowires, to efficiently modulate their surface potential. Thus, the sensors allow for a real-time assessment of the steroid biomarkers at low nanomolar concentration. The measurement platform is designed in a building-block concept, consisting of a modular measuring unit and a customizable biochip board, and operates using a complementary metal-oxide-semiconductor-integrated multiplexer. The platform is capable of continuous and simultaneous measurement of samples from multiple patients. Cortisol levels detected with the presented platform agreed well with the results obtained with a commercial high-sensitivity immunoassay.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
Kirschbaum, C., Pirke, K.-M., & Hellhammer, D. H. (2008) · Neuropsychobiology · doi:10.1159/000119004 · Cited by 6,093 · see citing works
Self-citationMultiplexed electrical detection of cancer markers with nanowire sensor arrays
Zheng, G., Patolsky, F., Cui, Y., Wang, W. U., & Lieber, C. M. (2005) · Nature Biotechnology · doi:10.1038/nbt1138 · Cited by 2,430 · see citing works
Salivary cortisol as a biomarker in stress research
Hellhammer, D. H., Wüst, S., & Kudielka, B. M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.10.026 · Cited by 1,925 · see citing works
Circular dichroism and conformational polymorphism of DNA
Kypr, J., Kejnovská, I., Renčiuk, D., & Vorlı́čková, M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp026 · Cited by 1,782 · see citing works
Hahm, J., & Lieber, C. M. (2003) · Nano Letters · doi:10.1021/nl034853b · Cited by 1,304 · see citing works
The effect of surface probe density on DNA hybridization
Peterson, A. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.24.5163 · Cited by 977 · see citing works
Importance of the Debye Screening Length on Nanowire Field Effect Transistor Sensors
Stern, E., Wagner, R., Sigworth, F. J., Breaker, R., Fahmy, T. M., & Reed, M. A. (2007) · Nano Letters · doi:10.1021/nl071792z · Cited by 806 · see citing works
Aptamer-field-effect transistors overcome Debye length limitations for small-molecule sensing
Nakatsuka, N., Yang, K., Abendroth, J., Cheung, K. M., Xu, X., Yang, H., Zhao, C., Zhu, B., Rim, Y., Yang, Y., et al. (2018) · Science · doi:10.1126/science.aao6750 · Cited by 793 · see citing works
Detection principles of biological and chemical FET sensors
Kaisti, M. (2017) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2017.07.010 · Cited by 581 · see citing works
Aptamers: Problems, Solutions and Prospects
Лахин, А. В., Tarantul, V. Z., & Gening, L. V. (2013) · Acta Naturae · doi:10.32607/20758251-2013-5-4-34-43 · Cited by 578 · see citing works
Subthreshold Regime has the Optimal Sensitivity for Nanowire FET Biosensors
Gao, X. P. A., Zheng, G., & Lieber, C. M. (2010) · Nano Letters · doi:10.1021/nl9034219 · Cited by 571 · see citing works
Label-free detection of small-molecule–protein interactions by using nanowire nanosensors
Wang, W. U., Chen, C., Lin, K.-H., Fang, Y. Z., & Lieber, C. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406368102 · Cited by 535 · see citing works
Peake, J. M., Kerr, G., & Sullivan, J. P. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00743 · Cited by 523 · see citing works
Development of a criteria set and a structured interview for disorders of extreme stress (SIDES)
Pelcovitz, D., van der Kolk, B. A., Roth, S., Mandel, F. S., Kaplan, S. J., & Resick, P. A. (1997) · Journal of Traumatic Stress · doi:10.1023/a:1024800212070 · Cited by 507 · see citing works
Silanes and Other Coupling Agents
(2020) · CRC Press eBooks · doi:10.1201/9780429070426 · Cited by 467 · see citing works
Silicon Nanowire Arrays for Label-Free Detection of DNA
Gao, Z., Agarwal, A., Trigg, A. D., Singh, N., Fang, C., Tung, C., Fan, Y., Buddharaju, K. D., & Kong, J. (2007) · Analytical Chemistry · doi:10.1021/ac061808q · Cited by 430 · see citing works
Cortisol in Saliva - Reference Ranges and Relation to Cortisol in Serum
Aardal, E., & Holm, A.-C. (1995) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1995.33.12.927 · Cited by 402 · see citing works
Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications
Ruscito, A., & DeRosa, M. C. (2016) · Frontiers in Chemistry · doi:10.3389/fchem.2016.00014 · Cited by 394 · see citing works
Graphene and Nanowire Transistors for Cellular Interfaces and Electrical Recording
Cohen‐Karni, T., Qing, Q., Li, Q., Fang, Y. Z., & Lieber, C. M. (2010) · Nano Letters · doi:10.1021/nl1002608 · Cited by 385 · see citing works
Zangheri, M., Cevenini, L., Anfossi, L., Baggiani, C., Simoni, P., Di Nardo, F., & Roda, A. (2015) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2014.08.048 · Cited by 373 · see citing works
Cortisol Effects on Body Mass, Blood Pressure, and Cholesterol in the General Population
Fraser, R., Ingram, M. C., Anderson, N., Morrison, C. E., Davies, E., & Connell, J. (1999) · Hypertension · doi:10.1161/01.hyp.33.6.1364 · Cited by 371 · see citing works
Biocompatible and Bioactive Surface Modifications for Prolonged In Vivo Efficacy
Meyers, S. R., & Grinstaff, M. W. (2011) · Chemical Reviews · doi:10.1021/cr2000916 · Cited by 294 · see citing works
Surface Charge Sensitivity of Silicon Nanowires: Size Dependence
Elfström, N., Juhasz, R., Sychugov, I., Engfeldt, T., Karlström, A. E., & Linnros, J. (2007) · Nano Letters · doi:10.1021/nl0709017 · Cited by 275 · see citing works
Smart, soft contact lens for wireless immunosensing of cortisol
Ku, M., Kim, J., Won, J., Kang, W., Park, Y., Park, J., Lee, J., Cheon, J., Lee, H. H., & Park, J. (2020) · Science Advances · doi:10.1126/sciadv.abb2891 · Cited by 274 · see citing works
Aptamer-based lateral flow assay for point of care cortisol detection in sweat
Dalirirad, S., & Steckl, A. J. (2018) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2018.11.161 · Cited by 260 · see citing works
Screening-Limited Response of NanoBiosensors
Nair, P. R., & Alam, M. A. (2008) · Nano Letters · doi:10.1021/nl072593i · Cited by 228 · see citing works
Miller, R., Stalder, T., Jarczok, M., Almeida, D. M., Badrick, E., Bartels, M., Boomsma, D. I., Coe, C. L., Dekker, M. C. J., Donzella, B., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.07.201 · Cited by 203 · see citing works
Self-citationIn Vivo Biosensing: Progress and Perspectives
Rong, G., Corrie, S. R., & Clark, H. A. (2017) · ACS Sensors · doi:10.1021/acssensors.6b00834 · Cited by 201 · see citing works
Silicon Nanoribbons for Electrical Detection of Biomolecules
Elfström, N., Karlström, A. E., & Linnros, J. (2008) · Nano Letters · doi:10.1021/nl080094r · Cited by 183 · see citing works
Type D personality: the heart, stress, and cortisol
Sher, L. (2005) · QJM · doi:10.1093/qjmed/hci064 · Cited by 167 · see citing works
Zhang, G., Chua, J. H., Chee, R.-E., et al. (2008) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2008.02.006 · Cited by 161 · see citing works
Hosseini, S. A., & Khalilzadeh, M. A. (2010) · International Conference on Biomedical Engineering and Computer Science · doi:10.1109/icbecs.2010.5462520 · Cited by 149 · see citing works
Cantilever-based sensing: the origin of surface stress and optimization strategies
Godin, M., Tabard‐Cossa, V., Miyahara, Y., et al. (2010) · Nanotechnology · doi:10.1088/0957-4484/21/7/075501 · Cited by 141 · see citing works
Tunable stringency aptamer selection and gold nanoparticle assay for detection of cortisol
Martin, J. A., Chávez, J. L., Chushak, Y. G., Chapleau, R. R., Hagen, J. A., & Kelley‐Loughnane, N. (2014) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-014-7883-8 · Cited by 120 · see citing works
Electrochemically Exfoliated High‐Quality 2H‐MoS2 for Multiflake Thin Film Flexible Biosensors
Zhang, P., Yang, S. H., Pineda‐Gómez, R., Ibarlucea, B., Ma, J., Lohe, M. R., Akbar, T. F., Baraban, L., Cuniberti, G., & Feng, X. (2019) · Small · doi:10.1002/smll.201901265 · Cited by 98 · see citing works
Self-citationA Study of Causes of Stress and Stress Management among Youth
Bhargava, D., & Trivedi, H. (2018) · IRA-International Journal of Management & Social Sciences · doi:10.21013/jmss.v11.n3.p1 · Cited by 97 · see citing works
Kim, K. S., Lee, H.-S., Yang, J., et al. (2009) · Nanotechnology · doi:10.1088/0957-4484/20/23/235501 · Cited by 94 · see citing works
Self-citationNegative Photoconductance in Heavily Doped Si Nanowire Field-Effect Transistors
Baek, E., Rim, T., Schütt, J., et al. (2017) · Nano Letters · doi:10.1021/acs.nanolett.7b02788 · Cited by 94 · see citing works
Phenylalanine Monitoring via Aptamer-Field-Effect Transistor Sensors
Cheung, K. M., Yang, K.-A., Nakatsuka, N., Zhao, C., Ye, M., Jung, M. E., Yang, H., Weiss, P. S., Stojanović, M. N., & Andrews, A. M. (2019) · ACS Sensors · doi:10.1021/acssensors.9b01963 · Cited by 89 · see citing works
Label free detection of plant viruses with organic transistor biosensors
Berto, M., Vecchi, E., Baiamonte, L., et al. (2018) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2018.10.080 · Cited by 86 · see citing works
Jang, H.-J., Lee, T., Song, J., Russell, L., Li, H., Dailey, J., Searson, P. C., & Katz, H. E. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b18855 · Cited by 80 · see citing works
Mitchell, J. S., Lowe, T. E., & Ingram, J. R. (2008) · The Analyst · doi:10.1039/b817083p · Cited by 79 · see citing works
Manickam, P., Pasha, S. K., Snipes, S. A., & Bhansali, S. (2016) · Journal of The Electrochemical Society · doi:10.1149/2.0781702jes · Cited by 78 · see citing works
Array feature size influences nucleic acid surface capture in DNA microarrays
Dandy, D. S., Wu, P., & Grainger, D. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606054104 · Cited by 76 · see citing works
Kim, K. S., Ryeol, L. S., Kim, S., Lee, J. Y., Chung, C., Choe, W., & Yoo, P. J. (2016) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2016.09.135 · Cited by 66 · see citing works
Self-citationDiamond electrolyte solution gate FETs for DNA and protein sensors using DNA/RNA aptamers
Kawarada, H., & Ruslinda, A. R. (2011) · physica status solidi (a) · doi:10.1002/pssa.201100503 · Cited by 65 · see citing works
Tran, D. P., Winter, M. A., Wolfrum, B. L., et al. (2016) · ACS Nano · doi:10.1021/acsnano.5b07136 · Cited by 57 · see citing works
The stress of life: a modern complaint?
Jackson, M. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60093-3 · Cited by 55 · see citing works
Nanowire sensors monitor bacterial growth kinetics and response to antibiotics
Ibarlucea, B., Rim, T., Baek, C., de Visser, J. A. G. M., Baraban, L., & Cuniberti, G. (2017) · Lab on a Chip · doi:10.1039/c7lc00807d · Cited by 53 · see citing works
Self-citationPlasmonic Biosensor Based on Vertical Arrays of Gold Nanoantennas
Klinghammer, S., Uhlig, T., Patrovsky, F., et al. (2018) · ACS Sensors · doi:10.1021/acssensors.8b00315 · Cited by 52 · see citing works
Self-citationChang, J., Zhou, G., Gao, X., Mao, S., Cui, S., Ocola, L. E., Yuan, C. Y., & Chen, J. (2015) · Sensing and Bio-Sensing Research · doi:10.1016/j.sbsr.2015.07.009 · Cited by 48 · see citing works
Ambulatory measurement of cortisol: Where do we stand, and which way to follow?
Hogenelst, K., Soeter, M., & Kallen, V. (2018) · Sensing and Bio-Sensing Research · doi:10.1016/j.sbsr.2018.100249 · Cited by 38 · see citing works
Jeon, D., Pregl, S., Park, S. J., et al. (2015) · Nano Letters · doi:10.1021/acs.nanolett.5b01188 · Cited by 37 · see citing works
Nanowire Field Effect Transistors: Principles and Applications
Kim, D. M., & Jeong, Y. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8124-9 · Cited by 37 · see citing works
Highly sensitive and rapid sequential cortisol detection using twin sensor QCM
Ito, T., Aoki, N., Kaneko, S., & Suzuki, K. A. O. (2014) · Analytical Methods · doi:10.1039/c4ay01387e · Cited by 32 · see citing works
Gang, A., Gabernet, G., Renner, L. D., et al. (2015) · RSC Advances · doi:10.1039/c5ra04469c · Cited by 30 · see citing works
Römhildt, L., Pahlke, C., Zörgiebel, F., et al. (2013) · ACS Applied Materials & Interfaces · doi:10.1021/am4038245 · Cited by 28 · see citing works
Bottom-up synthesis of ultrathin straight platinum nanowires: Electric field impact
Nerowski, A., Opitz, J. L., Baraban, L., et al. (2013) · Nano Research · doi:10.1007/s12274-013-0303-0 · Cited by 26 · see citing works
Self-citationGating Hysteresis as an Indicator for Silicon Nanowire FET Biosensors
Ibarlucea, B., Römhildt, L., Zörgiebel, F., et al. (2018) · Applied Sciences · doi:10.3390/app8060950 · Cited by 26 · see citing works
Tahara, Y., Huang, Z., Kiritoshi, T., Onodera, T., & Toko, K. (2014) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2014.00015 · Cited by 23 · see citing works
Klinghammer, S., Rauch, S., Pregl, S., Uhlmann, P., Baraban, L., & Cuniberti, G. (2020) · Micromachines · doi:10.3390/mi11030274 · Cited by 23 · see citing works
Self-citationKlopfenstein, B. J., Purnell, J. Q., Brandon, D. D., Isabelle, L. M., & DeBarber, A. E. (2010) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2010.12.008 · Cited by 19 · see citing works
Electrical Characteristics of Doped Silicon Nanowire Channel Field-Effect Transistor Biosensors
Rim, T., Kim, K., Cho, H., et al. (2016) · IEEE Sensors Journal · doi:10.1109/jsen.2016.2625420 · Cited by 14 · see citing works
Self-citationCMOS multiplexer for portable biosensing system with integrated microfluidic interface
Voitsekhivska, T., Suthau, E., & Wolter, K. (2014) · 2022 IEEE 72nd Electronic Components and Technology Conference (ECTC) · doi:10.1109/ectc.2014.6897285 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Shajari, S., Salahandish, R., Zare, A., Hassani, M., Moossavi, S., Munro, E., Rashid, R., Rosenegger, D., Bains, J. S., & Sanati Nezhad, A. (2023) · Advanced Science · doi:10.1002/advs.202204171 · Cited by 55 · see citing works
- Authors
- Klinghammer, S., Voitsekhivska, T., Licciardello, N., Kim, K., Baek, C.-K., Cho, H., Wolter, K.-J., Kirschbaum, C., Baraban, L., & Cuniberti, G.
- Affiliations
- Max Bergmann Center of Biomaterials (DE)
- Helmholtz-Zentrum Dresden-Rossendorf (DE)
- Pohang University of Science and Technology (KR)
- Technische Universität Dresden (DE)
- Corresponding author
- Baraban, Larysa
- ORCID
- Venue
- ACS Sensors
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-12-03
- Volume
- 5
- Issue
- 12
- Pages
- 4081-4091
- ISSN
- 2379-3694 (ISSN-L)
- OpenAlex
- W3110229389
- Cited by
- 62
- References
- 64
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 12 · 2023: 12 · 2022: 10 · 2021: 3
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Sensors (publishedVersion)
- PubMed (publishedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Physical Sciences › Engineering › Biomedical Engineering › Nanowire Synthesis and Applications
- Physical Sciences › Chemical Engineering › Bioengineering › Analytical Chemistry and Sensors
- Keywords
- cortisol, stress biomarkers, saliva, field-effect transistor sensors, nanowire sensors, DNA aptamers, label-free detection, real-time monitoring, steroid hormones, biochips, conformational change
- MeSH terms
- Humans, Saliva, Transistors, Electronic, Biosensing Techniques, Biomarkers, Nanowires
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review