Noninvasive Detection of Stress by Biochemical Profiles from the Skin

Elias Mansour, Eilam Palzur, Yoav Y. Broza, Walaa Saliba, Sharon Kaisari, Pavel Goldstein, Alon Shamir, Hossam Haick

Research output: Contribution to journalArticlepeer-review


Stress is a leading cause of several disease types, yet it is underdiagnosed as current diagnostic methods are mainly based on self-reporting and interviews that are highly subjective, inaccurate, and unsuitable for monitoring. Although some physiological measurements exist (e.g., heart rate variability and cortisol), there are no reliable biological tests that quantify the amount of stress and monitor it in real time. In this article, we report a novel way to measure stress quickly, noninvasively, and accurately. The overall detection approach is based on measuring volatile organic compounds (VOCs) emitted from the skin in response to stress. Sprague Dawley male rats (n = 16) were exposed to underwater trauma. Sixteen naive rats served as a control group (n = 16). VOCs were measured before, during, and after induction of the traumatic event, by gas chromatography linked with mass spectrometry determination and quantification, and an artificially intelligent nanoarray for easy, inexpensive, and portable sensing of the VOCs. An elevated plus maze during and after the induction of stress was used to evaluate the stress response of the rats, and machine learning was used for the development and validation of a computational stress model at each time point. A logistic model classifier with stepwise selection yielded a 66-88% accuracy in detecting stress with a single VOC (2-hydroxy-2-methyl-propanoic acid), and an SVM (support vector machine) model showed a 66-72% accuracy in detecting stress with the artificially intelligent nanoarray. The current study highlights the potential of VOCs as a noninvasive, automatic, and real-time stress predictor for mental health.

Original languageEnglish
Pages (from-to)1339-1347
Number of pages9
JournalACS Sensors
Issue number3
StatePublished - 24 Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.


  • behavioral
  • sensor
  • skin
  • stress
  • volatile organic compound

ASJC Scopus subject areas

  • Bioengineering
  • Instrumentation
  • Fluid Flow and Transfer Processes
  • Process Chemistry and Technology


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