Selective Breath Isoprene Detection By Filter-Enhanced Sensor
Authors: van den Broek Jan , Mochalski Paweł , Königstein Karsten , Wang Amy Chang Ting , Unterkofler Karl , Mayhew Chris A. , Guntner Andreas T. , Pratsinis Sotiris E. 
Published: July 2021

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 [3] 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]. Using a high-resolution mass spectrometer, the sensor is validated on >100 real breath samples during a protocol of exercise and rest.

Method

The isoprene sensor consists of a compact separation column placed upstream of a chemoresistive microsensor. The separation column is a packed bed of 50 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 [6], sensing nanoparticles of Si-doped WO3 (10 mol% Si) 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 350 °C by providing DC current to the back heater of the sensor substrate. The isoprene sensor is validated with breath of volunteers during rest and exercise (60% max. intensity) on an ergometer. Breath is monitored continuously through a mask connected to a proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS). For sensor measurements, breath samples of 25 mL were taken through a septum in the mask with a gas-tight syringe and exposed to the sensor through the filter for 60 s.

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.

When exposing the filter to breath for 60 s, only isoprene passes it without effect, while the hydrophilic analytes such as methanol and acetone are held back (Figure 2). In combination with the Si-doped WO3 microsensor, isoprene can be detected without interference (i.e., with very high selectivity). After a measurement, the filter can simply be exchanged or regenerated by flushing with room air for a few minutes.

At the onset of physical exercise, isoprene in breath spikes up to a factor of 4-5 within 1 min and quickly returns back to baseline within a few minutes [3]. The isoprene sensor can follow this fast dynamic of breath isoprene in good agreement to PTR-TOF-MS. In total, we evaluated 148 breath samples from 6 volunteers, showing good correlation (Pearson’s r = 0.89) of the isoprene sensor to PTR-TOF-MS. To our knowledge, this is the first validation of a breath isoprene sensor and is promising for a variety of applications including non-invasive measurement of blood cholesterol from breath.

References

[1] E.S. Deneris, R.A. Stein, J.F. Mead, Invitro biosynthesis of isoprene from mevalonate utilizing a rat liver cytosolic fraction, Biochemical and biophysical research communications. 123 (1984) 691-696.

[2] T. Karl, P. Prazeller, D. Mayr, A. Jordan, J. Rieder, R. Fall, W. Lindinger, Human breath isoprene and its relation to blood cholesterol levels: New measurements and modeling, Journal of Applied Physiology. 91 (2001) 762-770.

[3] J. King, A. Kupferthaler, K. Unterkofler, H. Koc, S. Teschl, G. Teschl, W. Miekisch, J. Schubert, H. Hinterhuber, A. Amann, Isoprene and acetone concentration profiles during exercise on an ergometer, Journal of Breath Research. 3 (2009) 027006.

[4] A.T. Güntner, S. Abegg, K. Königstein, P.A. Gerber, A. Schmidt-Trucksäss, S.E. Pratsinis, Breath Sensors for Health Monitoring, ACS Sensors. 4 (2019) 268-280.

[5] J. van den Broek, A.T. Güntner, S.E. Pratsinis, Highly selective and rapid breath isoprene sensing enabled by activated alumina filter, ACS Sensors. 3 (2018) 677-683.

[6] A.T. Güntner, N.A. Sievi, S.J. Theodore, T. Gulich, M. Kohler, S.E. Pratsinis, Noninvasive Body Fat Burn Monitoring from Exhaled Acetone with Si-doped WO3-sensing Nanoparticles, Analytical Chemistry. 89 (2017) 10578-10584.

Figure 1