Development of Real-Time Cuffless Blood Pressure Measurement Systems with ECG Electrodes and a Microphone Using Pulse Transit Time (PTT).

Research has shown that pulse transit time (PTT), which is the time delay between the electrocardiogram (ECG) signal and the signal from a photoplethysmogram (PPG) sensor, can be used to estimate systolic blood pressure (SBP) and diastolic blood pressure (DBP) without the need for a cuff. However, the LED of the PPG sensor requires the precise adjustment of both light intensity and light absorption rates according to the contact status of the light-receiving element. This results in the need for regular calibration. In this study, we propose a cuffless blood pressure monitor that measures real-time blood pressure using a microphone instead of a PPG sensor. The blood pulse wave is measured in the radial artery of the wrist using a microphone that can directly measure the sound generated by a body rather than sending energy inside the body and receiving a returning signal. Our blood pressure monitor uses the PTT between the R-peak of the ECG signal and two feature points of the blood pulse wave in the radial artery of the wrist. ECG electrodes and circuits were fabricated, and a commercial microelectromechanical system (MEMS) microphone was used as the microphone to measure blood pulses. The peak points of the blood pulse from the microphone were clear, so the estimated SBP and DBP could be obtained from each ECG pulse in real time, and the resulting estimations were similar to those made by a commercial cuff blood pressure monitor. Since neither the ECG electrodes nor the microphone requires calibration over time, the real-time cuffless blood pressure monitor does not require calibration. Using the developed device, blood pressure was measured three times daily for five days, and the mean absolute error (MAE) and standard deviation (SD) of the SBP and DBP were found to be 2.72 ± 3.42 mmHg and 2.29 ± 3.53 mmHg, respectively. As a preliminary study for proof-of-concept, these results were obtained from one subject. The next step will be a pilot study on a large number of subjects.

Development and Optimization of Silicon-Dioxide-Coated Capacitive Electrode for Ambulatory ECG Measurement System.

This paper presents a silicon-dioxide-coated capacitive electrode system for an ambulatory electrocardiogram (ECG). The electrode was coated with a nano-leveled (287 nm) silicon dioxide layer which has a very high resistance of over 200 MΩ. Due to this high resistance, the electrode can be defined as only a capacitor without a resistive characteristic. This distinct capacitive characteristic of the electrode brings a simplified circuit analysis to achieve the development of a high-quality ambulatory ECG system. The 240 um thickness electrode was composed of a stainless-steel sheet layer for sensing, a polyimide electrical insulation layer, and a copper sheet connected with the ground to block any electrical noises generated from the back side of the structure. Six different diameter electrodes were prepared to optimize ECG signals in ambulatory environment, such as the amplitude of the QRS complex, amplitude of electromagnetic interference (EMI), and baseline wandering of the ECG signals. By combining the experimental results, optimal ambulatory ECG signals were obtained with electrodes that have a diameter from 1 to 3 cm. Moreover, we achieved high-quality ECG signals in a sweating simulation environment with 2 cm electrodes.

Fermentative production and direct extraction of (-)-α-bisabolol in metabolically engineered Escherichia coli.

BACKGROUND: (-)-α-Bisabolol, also known as levomenol, is an unsaturated sesquiterpene alcohol that has mainly been used in pharmaceutical and cosmetic products due to its anti-inflammatory and skin-soothing properties. (-)-α-Bisabolol is currently manufactured mainly by steam-distillation of the essential oils extracted from the Brazilian candeia tree that is under threat because its natural habitat is constantly shrinking. Therefore, microbial production of (-)-α-bisabolol plays a key role in the development of its sustainable production from renewable feedstock. RESULTS: Here, we created an Escherichia coli strain producing (-)-α-bisabolol at high titer and developed an in situ extraction method of (-)-α-bisabolol, using natural vegetable oils. We expressed a recently identified (-)-α-bisabolol synthase isolated from German chamomile (Matricaria recutita) (titer: 3 mg/L), converted the acetyl-CoA to mevalonate, using the biosynthetic mevalonate pathway (12.8 mg/L), and overexpressed farnesyl diphosphate synthase to efficiently supply the (-)-α-bisabolol precursor farnesyl diphosphate. Combinatorial expression of the exogenous mevalonate pathway and farnesyl diphosphate synthase enabled a dramatic increase in (-)-α-bisabolol production in the shake flask culture (80 mg/L) and 5 L bioreactor culture (342 mg/L) of engineered E. coli harboring (-)-α-bisabolol synthase. Fed-batch fermentation using a 50 L fermenter was conducted after optimizing culture conditions, resulting in efficient (-)-α-bisabolol production with a titer of 9.1 g/L. Moreover, a green, downstream extraction process using vegetable oils was developed for in situ extraction of (-)-α-bisabolol during fermentation and showed high yield recovery (>98%). CONCLUSIONS: The engineered E. coli strains and economically viable extraction process developed in this study will serve as promising platforms for further development of microbial production of (-)-α-bisabolol at large scale.