Abstract
Early detection is critical to successfully eradicating a variety of cancers, so the development of a new cancer primary screening system is essential. Herein, we report an animal nose sensor system for the potential primary screening of lung cancer. To establish this, we developed an odor discrimination training device based on operant conditioning paradigms for detection of toluene, an odor indicator component of lung cancer. The rats (N = 15) were trained to jump onto a floating ledge in response to toluene-spiked breath samples. Twelve rats among 15 trained rats reached performance criterion in 12 consecutive successful tests within a given set, or over 12 sets, with a success rate of over 90%. Through a total of 1934 tests, the trained rats (N = 3) showed excellent performance for toluene detection with 82% accuracy, 83% sensitivity, 81% specificity, 80% positive predictive value (PPV) and 83% negative predictive value (NPV). The animals also acquired considerable performance for odor discrimination even in rigorous tests, validating odor specificity. Since environmental and long-term stability are important factors that can influence the sensing results, the performance of the trained rats was studied under specified temperature (20, 25, and 30 °C) and humidity (30%, 45%, and 60% RH) conditions, and monitored over a period of 45 days. At given conditions of temperature and humidity, the animal sensors showed an average accuracy within a deviation range of ±10%, indicating the excellent environmental stability of the detection rats. Surprisingly, the trained rats did not differ in retention of last odor discrimination when tested 45 days after training, denoting that the rats’ memory for trained odor is still available over a long period of time. When taken together, these results indicate that our odor discrimination training system can be useful for non-invasive breath testing and potential primary screening of lung cancer.
Highlights
The animal odor discrimination training system is composed of 5 units, as follows: (1) injection unit for delivering odors into the chamber; (2) ventilation unit for removing odor components remaining in the chamber; (3) sensing unit for recording altering behavior of animals in response to odors; (4) reinforcement unit for making odor-reward association by using a go/no-go operant conditioning paradigm; (5) Punishment unit for weakening undesirable responses of animals by presenting something unpleasant after the response
We report an animal nose sensor system for detecting toluene, one of lung cancer-related volatile organic compounds (VOCs)
We developed an odor discrimination training device for odor detection, which was designed with two major learning paradigms of reinforcement and punishment
Summary
The conditioned animal can quickly recognize the unique odor of volatile organic compounds, and exhibit particular signal behaviors, acting as an animal nose sensor. Animal nose sensors have mostly been applied in the field of drug detection [3,4] and mine/explosives detection [5,6,7] and, recently, in some medical applications, such as cancer detection [8,9,10] and tuberculosis detection [11,12]. With regard to cancer diagnosis, early diagnosis is especially important for successful treatment of cancer [13]. Analysis of volatile organic compounds (VOCs) released from human exhaled breath are becoming an important early diagnostic method that can be used for health evaluation [20,21]. Breath testing has the advantage of eliminating the invasive sample collection required to test for disease markers present in blood or tissue
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