Po-Jen Chien
Tokyo Medical and Dental University
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Featured researches published by Po-Jen Chien.
Biosensors and Bioelectronics | 2015
Ming Ye; Po-Jen Chien; Koji Toma; Takahiro Arakawa; Kohji Mitsubayashi
Several volatile organic compounds (VOCs) are released from human breath or skin. Like chemical substances in blood or urine, some of these vapors can provide valuable information regarding the state of the human body. A highly sensitive acetone biochemical gas sensor (bio-sniffer) was developed and used to measure exhaled breath acetone concentration, and assess lipid metabolism based on breath acetone analysis. A fiber-optic biochemical gas sensing system was constructed by attaching a flow-cell with nicotinamide adenine dinucleotide (NADH)-dependent secondary alcohol dehydrogenase (S-ADH) immobilized membrane onto a fiber-optic NADH measurement system. The NADH measurement system utilizes an ultraviolet-light emitting diode with peak emission of 335 nm as an excitation light source. NADH is consumed by the enzymatic reaction of S-ADH, and the consumption is proportional to the concentration of acetone vapor. Phosphate buffer which contained NADH was circulated into the flow-cell to rinse products and the excessive substrates from the optode. The change of fluorescent emitted from NADH is analyzed by the PMT. Hence, fluorescence intensity decreased as the acetone concentration increased. The relationship between fluorescence intensity and acetone concentration was identified from 20 ppb to 5300 ppb. This interval included the concentration of acetone vapor in the breath of healthy people and those suffering from disorders of carbohydrate metabolism. Finally, the acetone bio-sniffer was used to measure breath acetone during an exercise stress test on an ergometer after a period of fasting. The concentration of acetone in breath was shown to significantly increase after exercise. This biosensor allows rapid, highly sensitive and selective measurement of lipid metabolism.
Biosensors and Bioelectronics | 2017
Po-Jen Chien; Takuma Suzuki; Masato Tsujii; Ming Ye; Koji Toma; Takahiro Arakawa; Kohji Mitsubayashi
Exhaled breath analysis has attracted lots of researchers attention in the past decades due to its advantages such as its non-invasive property and the possibility of continuous monitoring. In addition, several volatile organic compounds in breath have been identified as biomarkers for some diseases. Particularly, studies have pointed out that concentration of isopropanol (IPA) in exhaled air might relate with certain illnesses such as liver disease, chronic obstructive pulmonary (COPD), and lung cancer. In this study, a highly sensitive and selective biochemical gas sensor (bio-sniffer) for the breath IPA concentration determination was constructed and optimized. This bio-sniffer measures the concentration of IPA according to the fluorescence intensity of oxidized nicotinamide adenine dinucleotide (NADH), which was produced by an enzymatic reaction of secondary alcohol dehydrogenase (S-ADH). The NADH detection system employed an UV-LED as the excitation light, and a highly sensitive photomultiplier tube (PMT) as a fluorescence intensity detector. A gas-sensing region was developed using an optical fiber probe equipped with a flow-cell and enzyme immobilized membrane, and connected to the NADH measurement system. The calibration range of the IPA bio-sniffer was confirmed from 1ppb to 9060ppb that was comparable to other IPA analysis methods. The results of the analysis of breath IPA concentration in healthy subjects using the bio-sniffer showed a mean concentration of 16.0ppb, which was similar to other studies. These results have demonstrated that this highly sensitive and selective bio-sniffer could be used to measure the IPA in exhaled air, and it is expected to apply for breath IPA research and investigation of biomarkers for clinical diagnosis.
Talanta | 2016
Po-Jen Chien; Ming Ye; Takuma Suzuki; Koji Toma; Takahiro Arakawa; Kohji Mitsubayashi
Isopropanol (IPA) is an important solvent used in industrial activity often found in hospitals as antiseptic alcohol rub. Also, IPA may have the potential to be a biomarker of diabetic ketoacidosis. In this study, an optical biosensor using NADH-dependent secondary alcohol dehydrogenase (S-ADH) for IPA measurement was constructed and evaluated. An ultraviolet light emitting diode (UV-LED, λ=340nm) was employed as the excitation light to excite nicotinamide adenine dinucleotide (NADH). A photomultiplier tube (PMT) was connected to a two-way branch optical fiber for measuring the fluorescence emitted from the NADH. S-ADH was immobilized on the membrane to catalyze IPA to acetone and reduce NAD(+) to be NADH. This IPA biosensor shows highly sensitivity and selectivity, the calibration range is from 500 nmol L(-1) to 1mmolL(-1). The optimization of buffer pH, temperature, and the enzyme-immobilized method were also evaluated. The detection of IPA in nail related cosmetic using our IPA biosensor was also carried out. The results showed that large amounts of IPA were used in these kinds of cosmetics. This IPA biosensor comes with the advantages of rapid reaction, good reproducibility, and wide dynamic range, and is also expected to use for clinical IPA detections in serum or other medical and health related applications.
ACS Sensors | 2017
Kenta Iitani; Po-Jen Chien; Takuma Suzuki; Koji Toma; Takahiro Arakawa; Kohji Mitsubayashi
Acetaldehyde (AcH) is found in ambient air, foods, and the living body. This toxic substance is also contained in wine and known as an important ingredient affecting the quality of wine. Herein, we constructed and evaluated two different fiber-optic biosensors for measurement of AcH in the liquid phase (AcH biosensor) using aldehyde dehydrogenase (ALDH) or alcohol dehydrogenase (ADH). The AcH biosensor measured a concentration of AcH using fluorescence intensity of a reduced form of nicotinamide adenine dinucleotide (NADH) that was produced or consumed via catalytic reaction of the respective enzyme. In the AcH measurement system, an ultraviolet light emitting diode (UV-LED) and photomultiplier tube (PMT) were connected to a bifurcated optical fiber and were used to excite and detect NADH. A sensing region was developed using an optical fiber probe and an enzyme-immobilized membrane, buffer pH, and concentrations of a coenzyme in buffer solution for ALDH forward reaction and ADH reverse reaction were optimized, and the dynamic ranges were compared. ADH-mediated AcH biosensor showed higher sensitivity, wider dynamic range (1-500 μM), and capability of rapid measurement (less than 3 min) than ALDH-mediated AcH biosensor (5-200 μM). ADH biosensor also presented a high selectivity and allowed measurement of AcH in 9 different wine samples (5 red and 4 white wines). The determined concentrations were comparable to those measured by NADH absorbance method, which validated the accuracy of the ADH biosensor in AcH measurement.
Biosensors and Bioelectronics | 2018
Takahiro Arakawa; Takuma Suzuki; Masato Tsujii; Kenta Iitani; Po-Jen Chien; Ming Ye; Koji Toma; Kohji Mitsubayashi
In this study, a highly sensitive and selective biochemical gas sensor (bio-sniffer) and real-time monitoring system with skin gas cell was constructed for the determination of ethanol gas concentration on human skin. This bio-sniffer measured the concentration of ethanol according to the change in fluorescence intensity of nicotinamide adenine dinucleotide (NADH), which is produced in an enzymatic reaction by alcohol dehydrogenase (ADH). The NADH detection system used an ultraviolet light emitting diode (UV-LED) as the excitation light, and a highly sensitive photomultiplier tube as a fluorescence intensity detector. The calibration range of the ethanol bio-sniffer was validated from 25 ppb to 128 ppm. To measure the concentration of ethanol within skin gas, subjects ingested an alcohol beverage, and the sensor output was monitored. We chose the central part of the palm, a back of the hand, and a wrist as targets. The real-time concentration of skin ethanol gas at each target was measured after drinking. The maximum output values were reached at approximately 70 min after drinking and then gradually decreased. We showed that ethanol release kinetics were different depending on the part of the hand measured with the developed monitoring system. Accordingly, this highly sensitive and selective bio-sniffer with a skin gas cell could be used to measure ethanol on the skin surface and could be applied for breath and skin gas research, as well as investigation of volatile blood compounds used as biomarkers for clinical diagnosis.
ACS Sensors | 2018
Kenta Iitani; Po-Jen Chien; Takuma Suzuki; Koji Toma; Takahiro Arakawa; Kohji Mitsubayashi
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.
IEEE Sensors Journal | 2017
Ming Ye; Takahiro Arakawa; Po-Jen Chien; Takuma Suzuki; Koji Toma; Kohji Mitsubayashi
A concentration of acetone in blood and urine can be used as a potential biomarker for clinical diagnosis such as diabetes mellitus type 1. In this paper, a fiber-optic biosensor exploiting consumption of nicotinamide adenine dinucleotide (NADH) was developed for determination of acetone concentration in an aqueous solution. An optical system for the biosensor was constructed with an ultraviolet-light emitting diode excitation system, a photomultiplier tube and an optical fiber probe. The biosensor was fabricated by attaching a membrane, where NADH-dependent secondary alcohol dehydrogenase (S-ADH) was immobilized to the fiber probe. Measurement of the acetone concentration was carried out by immersing the sensor probe in phosphate buffer solution, which contained a coenzyme, NADH. NADH was consumed by the enzymatic reaction with S-ADH, and the consumption was proportional to the acetone concentration. Fluorescence light emitted from NADH was then guided to the photomultiplier tube. Effect of the buffer pH and NADH concentration to the sensor performance, and the selectivity to acetone were also evaluated. As a result, the fluorescence intensity decreased as the acetone concentration increased. A relation between the change of fluorescence intensity and the acetone concentration was found from 0.2 to
SPIE BioPhotonics Australasia | 2016
Kohji Mitsubayashi; Po-Jen Chien; Ming Ye; Takuma Suzuki; Koji Toma; Takahiro Arakawa
50~\mu
The Japan Society of Applied Physics | 2018
Kanako Iwasaki; Po-Jen Chien; Koji Toma; Takahiro Arakawa; Kohji Mitsubayashi
mol/L using decrease phenomena of NADH fluorescence for determination of the acetone concentration. The highly sensitive and selective acetone biosensor is the potential tool for diagnosis of diabetes in near future.
The Japan Society of Applied Physics | 2017
Masato Tsujii; Takuma Suzuki; Po-Jen Chien; Ming Ye; Koji Toma; Takahiro Arakawa; Kohji Mitsubayashi
A fluorometric acetone biosniffer (biochemical gas sensor) for assessment of lipid metabolism utilizing reverse reaction of secondary alcohol dehydrogenase was constructed and evaluated. The biosniffer showed highly sensitivity and selectivity for continuous monitoring of gaseous acetone. The measurement of breath acetone concentration during fasting and aerobic exercise were also investigated. The acetone biosniffer provides a novel analytical tool for noninvasive evaluation of human lipid metabolism and it is also expected to use for the clinical and physiological applications such as monitoring the progression of diabetes.