Abstract

Introduction Breath analysis enables revolutionary, on-demand detection and monitoring of health parameters in a noninvasive and personalized fashion. Breath isoprene is a byproduct of the cholesterol biosynthetic pathway [1] and has been shown to decrease during a cholesterol lowering therapy [2]. However, altered breath isoprene levels can indicate a variety of pathological and physiological states in the human body such as muscle activity, influenza [3], end-stage renal disease, lung cancer or liver disease with advanced fibrosis. Thus, accurate measurement and monitoring of breath isoprene levels by a breath analyzer are promising for non-invasive detection or monitoring of such conditions.Chemical gas sensors are simple to use, offer low cost and high miniaturization potential, and they can detect volatile organic compounds at ppb concentrations [4]. However, they are typically not selective enough to monitor isoprene in a complex gas mixture such as breath. Here, we address this by combining a micromachined gas sensor with a miniaturized separation column of activated alumina [5]. Method The isoprene sensor consists of a compact separation column placed upstream of a chemoresistive microsensor. The separation column is a packed bed of 100 mg activated alumina (50–300 mesh, ~155 m2 g-1) inside a Teflon tube (4 mm inner diameter) and secured on both ends with silanized quartz wool. For the sensor, sensing nanoparticles of Pt-doped SnO2 (0.1 mol% Pt) are produced by flame-spray pyrolysis (FSP) and deposited directly onto micromachined sensor substrates (1.9 x 1.7 mm2) by thermophoresis. Sensing films are heated to 400 °C by providing DC current to the back heater of the sensor substrate. The isoprene sensor is characterized with synthetic gas mixtures using a dynamic mixing setup. Results and Conclusions Figure 1 shows the isoprene sensor consisting of a compact filter placed upstream of a chemoresistive microsensor. The filter contains a polar adsorbent that retains hydrophilic compounds (e.g., ketones, alcohols, ammonia) —representing major interferants in breath and ambient air—while hydrophobic isoprene is not affected and detected selectively by the highly sensitive microsensor. Commercial activated alumina is used as sorbent offering high surface area (~155 m2 g-1) and polarity, resulting in compact (1 cm length) and inexpensive (<1 $) filters. The microsensor is heated by a free-standing membrane-type heater, offering low power requirement (only 85 mW at 400 °C) suitable for battery-driven operation.The filter does not retain isoprene, which is detected by the sensor with fast response and recovery times (5 and 10 s, respectively). The flame-made Pt-doped SnO2 sensor is highly sensitive due to its porous and nanostructured morphology, enabling detection of only 5 ppb of isoprene with high signal-to-noise ratio (>90). When exposing the sensor with filter to 60 s pulses of 1 ppm isoprene, acetone, methanol and ethanol, only isoprene is detected during the exposure, while the hydrophilic analytes are held back (Figure 2). As a result, isoprene is detected without interference (i.e., with very high selectivity). Even when operated continuously for eight days, this sensor showed stable performance with reproducible (regeneration within 10 min) and accurate isoprene detection in simulated breath mixtures composed of breath-relevant concentrations of isoprene, acetone, methanol and ammonia.The filter is modular and, based on its small size and low price, can be readily integrated into inexpensive and portable isoprene detectors. This is promising for non-invasive measurement of blood cholesterol levels from.

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