(Invited) Bio-Sniffers & Sniff-Cam: Biofluorometirc Gas Sensor and Imaging System for Human Volatile Chemicals

Abstract

Introduction Various volatile organic compounds exist, such as those the transpired by humans, breath, body odor and smell of the living environment. The human body emits various volatile molecules, depending on a person’s genetics, disease and metabolic condition. In this contribution, novel gas-phase biosensors (bio-sniffer and sniff-cam) using bio-fluorometric techniques for human volatiles will be introduced as a future biosensing approach for preemptive medicine and healthcare. Bio-sniffer for breath acetone as early screening approach of diabetes mellitus. Secondary alcohol dehydrogenase (S-ADH) catalyzes the reduction of acetone and the oxidation of nicotinamide adenine dinucleotide (NADH to NAD+) in a weak acid environment (Fig.1). NADH is excited by 340 nm excitation lights and subsequently emit 490 nm fluorescence. Therefore, acetone can be measured by the decrease in NADH fluorescence intensity. A bio-fluorometric acetone sniffer was constructed by incorporating an optic-probe into a gas/liquid flow cell with S-ADH immobilized diaphragm (Fig.2) [1,2]. The developed biosniffer show rapid response, highly sensitivity and selectivity to acetone. The breath acetone analysis in healthy subjects shows that the mean values were 750.0 ± 434.4 ppb. The breath acetone did not show a statistical difference among different genders and ages. The breath acetone analysis for diabetic patients under medical treatment shows a mean value of 1207.7 ± 689.5 ppb, which was higher than that of healthy subjects (p < 1 × 10−6). In particularly, type-1 diabetic (T1D) patients exhaled a much higher concentration of acetone than type-2 diabetic (T2D) patients (p < 0.01) (Fig.3). These findings are worthwhile in the study of breath biomarkers for early screening of diabetes mellitus. Additionally, the developed bio-sniffers provide a new technique for volatolomics research. Sniff-cam with biofluorometric technique for spatiotemporal gas imaging A decade ago, a chemiluminescence sniff-cam system was developed and applied successfully for distribution imaging of high concentration ethanol vapor (ppm-level) such as breath ethanol after drinking (Fig.4) [3] and wine aroma from wine glass (Fig.5) [4]. In order to improve the performance, we applied the bio-fluorometric technique for highly sensitive sniff-cam system (ppb-level). The sniff-cam with ADH (alcohol dehydrogenase) redox reactions can show a spatiotemporal change of gaseous ethanol (EtOH) or acetaldehyde (AcH) in real-time [5,6]. The sniff-cam was composed of a highly sensitive camera, a UV-LED array sheet, and an ADH-immobilized mesh. The both redox reactions of ADH were employed for detection of gaseous EtOH and AcH where a relationship between fluorescence intensity from nicotinamide adenine dinucleotide. Moreover, the image differentiation method that calculated a fluorescence change rate was employed to visualize a real-time change in the concentration distribution of EtOH and AcH. The dynamic ranges of the sniff-cam for EtOH and AcH were 20ppb-300ppm and 100 ppb-10 ppm. As the physiological application, the sniff-cam successfully achieved the imaging of the concentration distribution of EtOH and AcH in breath and skin gas (Fig. 6). Future potential of the gas-phase biosensors (bio-sniffer and sniff-cam) The future potential of the bio-sniffer and sniff-cam for body volatiles includes the early disease screening, the identification of those locations, the real time evaluation of metabolic condition as a Bio-IoT monitoring.