Fiber-Optic Bio-sniffer (Biochemical Gas Sensor) Using Reverse Reaction of Alcohol Dehydrogenase for Exhaled Acetaldehyde

Abstract

Volatile organic compounds (VOCs) exhaled in breath have huge potential as indicators of diseases and metabolisms. Application of breath analysis for disease screening and metabolism assessment is expected since breath samples can be noninvasively collected and measured. In this research, a highly sensitive and selective biochemical gas sensor (bio-sniffer) for gaseous acetaldehyde (AcH) was developed. In the AcH bio-sniffer, a reverse reaction of alcohol dehydrogenase (ADH) was employed for reducing AcH to ethanol and simultaneously consuming a coenzyme, reduced form of nicotinamide adenine dinucleotide (NADH). The concentration of AcH can be quantified by fluorescence detection of NADH that was consumed by reverse reaction of ADH. The AcH bio-sniffer was composed of an ultraviolet light-emitting diode (UV-LED) as an excitation light source, a photomultiplier tube (PMT) as a fluorescence detector, and an optical fiber probe, and these three components were connected with a bifurcated optical fiber. A gas-sensing region of the fiber probe was developed with a flow-cell and an ADH-immobilized membrane. In the experiment, after optimization of the enzyme reaction conditions, the selectivity and dynamic range of the AcH bio-sniffer were investigated. The AcH bio-sniffer showed a short measurement time (within 2 min) and a broad dynamic range for determination of gaseous AcH, 0.02-10 ppm, which encompassed a typical AcH concentration in exhaled breath (1.2-6.0 ppm). Also, the AcH bio-sniffer exhibited a high selectivity to gaseous AcH based on the specificity of ADH. The sensor outputs were observed only from AcH-contained standard gaseous samples. Finally, the AcH bio-sniffer was applied to measure the concentration of AcH in exhaled breath from healthy subjects after ingestion of alcohol. As a result, a significant difference of AcH concentration between subjects with different aldehyde dehydrogenase type 2 (ALDH2) phenotypes was observed. The AcH bio-sniffer can be used for breath measurement, and further, an application of breath analysis-based disease screening or metabolism assessment can be expected due to the versatility of its detection principle, which allows it to measure other VOCs by using NADH-dependent dehydrogenases.

Biochemical Methanol Gas Sensor (MeOH Bio-Sniffer) for Non-Invasive Assessment of Intestinal Flora from Breath Methanol

“…The device configuration of the MeOH bio-sniffer was similar to the ones in our previous studies except for the membrane [ 39 , 43 , 44 ]. Briefly, it consisted of a bifurcated optical fiber (PVSMA2-2 STU600-STUH190S, Mitsubishi Cable Industries, Tokyo, Japan), an optical fiber probe (F1000-900, Ocean Insight, Orlando, FL, USA), a UV light emitting diode (UV-LED, UF4LU-0GD01, DOWA, Tokyo, Japan), and a photomultiplier tube (PMT, C9692-11, Hamamatsu Photonics, Shizuoka, Japan).…”

“…First, waterproofing was made on the gas phase side of the membrane, which was opposite to the side of AOD and FALDH being immobilized, because the AOD-FALDH membrane was hydrophilic, and thus, the NAD + solution in the flow-cell had leaked into The device configuration of the MeOH bio-sniffer was similar to the ones in our previous studies except for the membrane [39,43,44]. Briefly, it consisted of a bifurcated optical fiber (PVSMA2-2 STU600-STUH190S, Mitsubishi Cable Industries, Tokyo, Japan), an optical fiber probe (F1000-900, Ocean Insight, Orlando, FL, USA), a UV light emitting diode (UV-LED, UF4LU-0GD01, DOWA, Tokyo, Japan), and a photomultiplier tube (PMT, C9692-11, Hamamatsu Photonics, Shizuoka, Japan).…”

“…Therefore, a sensor for MeOH in exhaled breath needs to be highly sensitive to MeOH as well as insensitive to humidity. Our biochemical gas sensor (bio-sniffer) has shown those required characteristics in previous studies for ethanol, acetaldehyde, isopropanol, and acetone [ 38 , 39 , 40 , 41 ], and in this study, we combined the advantages of the bio-sniffer and AOD-FALDH cascade reaction to measure MeOH in exhaled breath.…”

A Bio-Fluorometric Acetone Gas Imaging System for the Dynamic Analysis of Lipid Metabolism in Human Breath

“…Representative VOCs in exhaled breath have been identified as possible diagnostic markers for various diseases. For example, acetone, ammonia, isoprene, 2-propanol, cyclohexanone, hydrogen sulfide, nitric oxide, ethane, carbon monoxide, acetaldehyde, and formaldehyde have been associated with disease [3,[34][35][36][37][38][39]. High-sensitivity analysis or measurement of these volatile biological components are employed for medical diagnostics and disease screening.…”

Polymer-Modified Quartz Tuning Forks for Breath Biomarker Sensing

“…[9]. Gas sensors such as optical gas sensors [10], mass-sensitive gas sensors [11,12], chemiresisitve sensors [13], and SAW detectors [14] are reportedly used to identify type or concentration of VOC biomarkers. However, these techniques are expensive and often operate at high temperatures.…”