Selective Breath Sensors for Metabolic Monitoring

Abstract

Introduction Despite a growing diagnostic toolset and a plethora of preventative and therapeutic interventions, a major challenge remains the control of epidemic diseases like obesity, diabetes or cancer. Great promise bears the current transformation of healthcare from disease-reactive to predictive, preventive, personalized and participatory - the so-called “4P” medicine [1]. Breath analysis could play a key role in this by providing on-demand critical health data. For daily breath analysis in wide-spread populations, simple-in-use and portable breath detectors are required. For this purpose, chemoresistive sensors are quite attractive due to their compact design, low cost and low power consumption being ideal for integration into handheld devices [2]. Here, I will describe recent progress on the development of selective/single-molecule breath sensors. In particular, I will showcase our recent in-vivo tests of Si-doped WO3 breath acetone sensors in a clinical environment during ketogenic dieting (KD) [3]. Finally, I will update on our newest development on orthogonal sensor arrays and present their application to sniff breath- and skin-emitted tracers (including acetone, isoprene and ammonia) for search & rescue applications [4]. Methods The sensor is based on a Si-doped WO3 nanoparticle films prepared by flame spray pyrolysis (FSP). Obtained nanoparticles were deposited directly by thermophoresis onto interdigitated Pt electrodes. End-tidal breath was extracted in a monitored and reproducible fashion with a tailor-made and modular sampler described in detail elsewhere [5]. The acetone sensor was mounted on a Macor holder, installed inside a Teflon chamber and fed with 130 mL min-1 from the sampler with a pump (SP 135 FZ, Schwarzer Precision). An additional line was connected just before the acetone sensor chamber to extract samples for the QMS (QMS 422, ThermoStarTM, Pfeiffer Vacuum). Healthy non-smokers free from respiratory or cardiovascular disease were included in this study. Each volunteer was informed about the experimental protocol prior to the test, gave written consent and could interrupt the test or withdraw consent anytime. The participants followed a fat:(carbohydrate+protein) 4:1 KD based on the Johns Hopkins protocol for 36 h including overnight fasting periods. Results and Conclusions Eleven volunteers (five female and six male) with a median age (± SD) of 22.7 (± 2.0) years participated in this study. Their body mass index was 22.4 (± 3.3) kg/m2. All volunteers had office jobs and were rather inactive. With the compact and inexpensive sensor, the individual breath acetone dynamics were monitored accurately up to concentrations of 66 ppm, in good agreement with mass spectrometry. The breath acetone dynamic reflected well the status of ketosis, as indicated by blood BOHB. Most interestingly, strong differences in individual breath and blood profiles were identified between the volunteers despite identical KD conditions. These were correctly recognized by the breath acetone sensor including patterns possibly associated to low tolerance to the KD protocol.As a result, this breath sensor is promising as a portable ketosis monitor. It has broad application as ketogenic diet is a proven medical treatment of refractory epilepsy (i.e. drug-resistant) [6] occurring in ~30% of the approx. 50 million epileptics worldwide. Also, it is an effective therapy for weight loss with growing interest to treat obesity-associated metabolic disorders [7] (e.g. diabetes or fatty liver disease), acts anti-inflammatory [8] and is even beneficial for athletes to improve their endurance performance by altering fuel preference [9].