Theoretical and experimental mechanistic study of water molecule involvement in the Prilezhaev reaction.

The Prilezhaev reaction produces epoxides using alkenes and peroxy acids such as m-chloroperoxybenzoic acid (mCPBA). The reaction proceeds via a concerted mechanism in one step. Although the mCPBA used in organic syntheses contains water because of its explosive nature, the effects of water on the reaction have not been considered. To investigate the effects of water on the reaction mechanism, we determined the thermodynamic parameters for the Prilezhaev reaction between styrene and mCPBA. The activation free energies, including solvent effects, were calculated using the SMD and QM/MC/FEP methods. The calculated thermodynamic parameters for the reaction directly involving two water molecules were in better agreement with the experimental data than those for the concerted mechanism. This result indicated that water molecules are involved in the progression of the mCPBA-mediated Prilezhaev reaction in solvents containing water molecules.

NIR spectroscopic determination of urine components in spot urine: preliminary investigation towards optical point-of-care test.

Presently, there is no convenient method to measure 24-h urinary Na excretion, which is an important index of daily Na intake, and 24-h urine collection involves a complex process. However, the Na-to-creatinine ratio (NCR) in spot urine has the potential to evaluate 24-h Na excretion and is useful for point-of-care testing. Thus, this study aimed to realize a near-infrared spectroscopic system to assess NCR in spot urine: (1) We attempted to estimate Na concentration using fewer than 10 wavelengths; (2) we calculated NCR using creatinine concentrations from our previous report and verified the NCR predictability. A calibration model was created using multi-linear regression analysis using 10 selected wavelengths in the range of Fourier-transform infrared spectrometer. Spot urine samples were obtained from healthy adults, and glucose powder was added to them to simulate diabetic samples. NCR was calculated using only six wavelengths, and the results confirmed the high accuracy of the estimated Na concentration even though inorganic components do not absorb near-infrared light. Our method enables to optically estimate NCR in spot urine, and it will be useful for point-of-care testing. Graphical abstract.

Adaptive control with self-tuning for non-invasive beat-by-beat blood pressure measurement.

Up to now, we have successfully carried out the non-invasive beat-by-beat measurement of blood pressure (BP) in the root of finger, superficial temporal and radial artery based on the volume-compensation technique with reasonable accuracy. The present study concerns with improvement of control method for this beat-by-beat BP measurement. The measurement system mainly consists of a partial pressurization cuff with a pair of LED and photo-diode for the detection of arterial blood volume, and a digital self-tuning control method. Using healthy subjects, the performance and accuracy of this system were evaluated through comparison experiments with the system using a conventional empirically tuned PID controller. The significant differences of BP measured in finger artery were not showed in systolic (SBP), p=0.52, and diastolic BP (DBP), p=0.35. With the advantage of the adaptive control with self-tuning method, which can tune the control parameters without disturbing the control system, the application area of the non-invasive beat-by-beat measurement method will be broadened.

Development of a ubiquitous healthcare monitoring system combined with non-conscious and ambulatory physiological measurements and its application to medical care.

The demand for ubiquitous healthcare monitoring has been increasingly raised for prevention of lifestyle-related diseases, acute life support or chronic therapies for inpatients and/or outpatients having chronic disorder and home medical care. From these view points, we developed a non-conscious healthcare monitoring system without any attachment of biological sensors and operations of devices, and an ambulatory postural changes and activities monitoring system. Furthermore in this study, in order to investigate those applicability to the ubiquitous healthcare monitoring, we have developed a new healthcare monitoring system combined with the non-conscious and the ambulatory measurements developed by us. In patients with chronic cardiovascular disease or stroke, the daily health conditions such as pulse, respiration, activities and so on, could be continuously measured in the hospital, the rehabilitation room and subject's own home, using the present system. The results demonstrated that the system appears useful for the ubiquitous healthcare monitoring not only at medical facility, but also during daily living at home.

Multivariate regression and discreminant calibration models for a novel optical non-invasive blood glucose measurement method named pulse glucometry.

A novel optical non-invasive in vivo blood glucose concentration (BGL) measurement technique, named "Pulse Glucometry", was combined with a kernel method; support vector machines. The total transmitted radiation intensity (I(lambda)) and the cardiac-related pulsatile changes superimposed on I(lambda) in human adult fingertips were measured over the wavelength range from 900 to 1700 nm using a very fast spectrophotometer, obtaining a differential optical density (DeltaOD(lambda)) related to the blood component in the finger tissues. Subsequently, a calibration model using paired data of a family of DeltaOD(lambda)s and the corresponding known BGLs was constructed with support vector machines (SVMs) regression instead of using calibration by a conventional primary component regression (PCR) and partial least squares regression (PLS). Secondly, SVM method was applied to make a nonlinear discriminant calibration model for "Pulse glucometry." Our results show that the regression calibration model based on the support vector machines can provide a good regression for the 101 paired data, in which the BGLs ranged from 89.0-219 mg/dl (4.94-12.2 mmol/l). The resultant regression was evaluated by the Clarke error grid analysis and all data points fell within the clinically acceptable regions (region A: 93%, region B: 7%). The discriminant calibration model using SVMs also provided a good result for classification (accuracy rate 84% in the best case).

Attempt of a novel calibration method of pulse oximetry using support vector machines regression.

A novel calibration method using support vector machines regression (SVMsR) of pulse oximetry was proposed and attempted. Conventional calibration method of pulse oximetry that based on an optical density ratio of transmitted visible red light and infrared radiation whereas a proposed method here was not based on the optical density ratio directly. In theory, conventional calibrations using the ratio can be considered as a technique for nonlinear problem: nonlinear relation between two optical densities (red and IR) and oxygen saturation could be linearized by the ratio calculation. We thought, that nonlinear problem could be solved by using nonlinear analyses. Among them, the support vector machines regression method that has been studied well in this decade was attempted to be applied for pulse oximetry calibration. As an experiment, two photo plethysmograms (PPGs) by red and IR were measured on five subjects. Simultaneously, oxygen saturation (SpO(2)) level was measured by a commercial pulse oxymeter. SpO(2)) level was controlled by breathing 10% oxygen gas obtaining 98-75% SpO(2) level. Sequentially, feature points of two PPGs were extracted in beat by beat. Convex peaks and concave valleys on waveform and DC levels of PPGs were selected as feature points. Then, nonlinear regression using SVMs were attempted to obtain relationship between SpO2 by meter (regressand) and feature points of PPG (regressor). In result, a regression model was constructed from training data that is three fourths of measured cardiac data by using SVMsR. Finally, the constructed calibration model was evaluated by other one third data (validation data). The root mean squared error for the validation data is 1.90 [SpO(2)) level %] and 89% of validation data fell within +/- 2 % of SpO(2) level by the meter. In conclusion, SVMsR might be applicable on calibration for pulse oximetry.

A fully automated health-care monitoring at home without attachment of any biological sensors and its clinical evaluation.

Daily monitoring of health condition is important for an effective scheme for early diagnosis, treatment and prevention of lifestyle-related diseases such as adiposis, diabetes, cardiovascular diseases and other diseases. Commercially available devices for health care monitoring at home are cumbersome in terms of self-attachment of biological sensors and self-operation of the devices. From this viewpoint, we have been developing a non-conscious physiological monitor installed in a bath, a lavatory, and a bed for home health care and evaluated its measurement accuracy by simultaneous recordings of a biological sensors directly attached to the body surface. In order to investigate its applicability to health condition monitoring, we have further developed a new monitoring system which can automatically monitor and store the health condition data. In this study, by evaluation on 3 patients with cardiac infarct or sleep apnea syndrome, patients' health condition such as body and excretion weight in the toilet and apnea and hypopnea during sleeping were successfully monitored, indicating that the system appears useful for monitoring the health condition during daily living.

Fiber-packed needle-type sample preparation device designed for gas chromatographic analysis.

A miniaturized sample preparation technique that uses a fine-fiber-packed needle as the extraction medium is reviewed, especially in relation to its application to the analysis of volatile organic compounds by gas chromatography. When the needle was packed longitudinally with a bundle of fine filaments (12 microm o.d.) which were also surface-coated with polymeric materials, successful sample preconcentration was obtained. Improved sensitivity was also established by introducing simultaneous derivatization reactions into the extraction process in the fiber-packed needle. The storage performance of the needle clearly demonstrated the potential of the technique for typical on-site sampling during environmental analysis. In this short review, the fiber-packed extraction needle developed by the authors is summarized along with applications that use the fiber-packed needle as a miniaturized extraction device.

Rapid determination of ethylene oxide with fiber-packed sample preparation needle.

Fiber-packed sample preparation device was applied to the simultaneous derivatization/preconcentration of ethylene oxide (EO) in air samples. The polymer-coated filaments were packed longitudinally into the needle, and hydrogen bromide (HBr) was loaded onto the filaments in the preconditioning process. Simultaneous derivatization with HBr in the needle was made during the sampling process of the gaseous EO, and the corresponding derivatized analyte, 2-bromoethanol, was desorbed by passing a small amount of methanol through the extraction needle in the heated gas chromatograph (GC) injector. The basic extraction/desorption parameters for EO have been evaluated. The limit of detection (LOD), limit of quantification (LOQ) and the relative standard deviation (RSD) of run-to-run repeatability were 1.8 ng/L, 5.4 ng/L and less than 4%, respectively, with an extraction time of about 10 min. Satisfactory storage performance for three days at room temperature was also confirmed.

Support vector machines as multivariate calibration model for prediction of blood glucose concentration using a new non-invasive optical method named Pulse Glucometry.

A novel optical non-invasive in vivo blood glucose concentration (BGL) measurement technique, named "Pulse Glucometry", was combined with a kernel method; support vector machines. The total transmitted radiation intensity (I lambda) and the cardiac-related pulsatile changes superimposed on I lambda in human adult fingertips were measured over the wavelength range from 900 to 1700 nm using a very fast spectrophotometer, obtaining a differential optical density (delta OD lambda) related to the blood component in the finger tissues. Subsequently, a calibration model using paired data of a family of delta OD lambda s and the corresponding known BGLs was constructed with support vector machines regression instead of using calibration by a conventional partial least squares regression (PLS). Our results show that the calibration model based on the support vector machines can provide a good regression for the 183 paired data, in which the BGLs ranged from 89.0-219 mg/dl (4.94-12.2 mmol/l). The resultant regression was evaluated by the Clarke error grid analysis and all data points fell within the clinically acceptable regions (region A: 93%, region B: 7%).

A flexible and wearable biosensor for tear glucose measurement.

A flexible and wearable amperometoric glucose sensor was fabricated and tested. Also, the sensor was utilized to tear glucose monitoring. The sensor was constructed by immobilizing GOD onto a flexible oxygen electrode (Pt working electrode and Ag/AgCl counter/reference electrode), which was fabricated using "Soft-MEMS" techniques onto a functional polymer membrane. In purpose of bioinstrumentation, adhesive agents were not used for constructing the flexible biosensor. Linear relationship between glucose concentration and output current was obtained in a range of 0.025-1.475 mmol/l, with a correlation coefficient of 0.998. Current dependences on pH and temperature were also evaluated. The current was largest at pH 7.0 and the current increased when temperature increased. This indicates that the output current depends on enzyme activity. Based on the basic characteristics investigation, the glucose sensor was applied to measurement of glucose in tear fluids on an eye site of a Japan white rabbit. The change of tear glucose level induced by oral-administration of glucose was monitored as a current change of the sensor attached on the eye site. In this investigation, the tear glucose level varied from 0.16 to 0.46 mmol/l. Although there was a delay of several tens of minutes towards blood sugar level, it is considered to be possible that non-invasive continuous glucose monitoring can be realized using the flexible biosensor.

Fiber-packed needle for dynamic extraction of aromatic compounds.

A fiber-packed needle was developed as a novel extraction device for gas-chromatographic analysis of trace organic compounds in aqueous samples. In the extraction device, a bundle of the polymer-coated filaments as the sorbent material was longitudinally packed into a specially designed needle. The extraction was made by pumping the aqueous sample solution into the needle extraction device, and the subsequent desorption process was carried out with a flow of desorption solvent through the needle in a heated gas chromatograph injector. The needle device showed an excellent thermal stability for repeated use without any deterioration of extraction performance, and no carryover effect was observed after the optimization of the desorption conditions. Additionally, the extraction efficiency of the fiber-packed needle could be enhanced by optimizing the number of packed filaments. The selectivity for various compounds could be also tuned using an appropriate combination of the fibrous medium and the coating polymer. The relative standard deviation for run to run was from 3.88 to 4.55% (n = 5), and that for needle to needle was 7.21% (n = 3), clearly suggesting a good repeatability of the needle extraction technique developed. Upon successful optimization of the extraction conditions, a rapid extraction of trace organic compounds from an aqueous sample matrix was successfully demonstrated, where each extraction process was completed within 10 min.

Miniaturized sample preparation needle: a versatile design for the rapid analysis of smoking-related compounds in hair and air samples.

Miniaturized needle extraction device has been developed as a versatile sample preparation device designed for the rapid and simple analysis of smoking-related compounds in smokers' hair samples and environmental tobacco smoke. Packed with polymeric particle, the resulting particle-packed needle was employed as a miniaturized sample preparation device for the analysis of typical volatile organic compounds in tobacco smoke. Introducing a bundle of polymer-coated filaments as the extraction medium, the needle was further applied as a novel sample preparation device containing simultaneous derivatization/extraction process of volatile aldehydes. Formaldehyde (FA) and acetaldehyde (AA) in smoker's breath during the smoking were successfully derivatized with two derivatization reagents in the polymer-coated fiber-packed needle device followed by the separation and determination in gas chromatography (GC). Smokers' hair samples were also packed into the needle, allowing the direct extraction of nicotine from the hair sample in a conventional GC injector. Optimizing the main experimental parameters for each technique, successful determination of several smoking-related compounds with these needle extraction methods has been demonstrated.

Simultaneous derivatization/preconcentration of volatile aldehydes with a miniaturized fiber-packed sample preparation device designed for gas chromatographic analysis.

A novel in-needle sample preparation device has been developed for the determination of volatile aldehydes in gaseous samples. The needle device is designed for the gas chromatographic (GC) analysis of aldehydes and ketones commonly found in typical in-house environments. In order to prepare the extraction device, a bundle of polymer-coated filaments was longitudinally packed into a specially designed needle. Derivatization reactions were prompted by 2,4-dinitrophenylhydrazine (NDPH) included in the needle, and so the aldehydes and ketones were derivatized to the corresponding hydrazones and extracted with the extraction needle. A reproducible extraction needle preparation process was established, along with a repeatable derivatization/extraction process that ensures the successful determination of aldehydes. The storage performance of the extraction needle was also evaluated at room temperature for three days. The results demonstrate the successful application of the fiber-packed extraction device to the preparation of a gaseous sample of aldehydes, and the future possibility of applying the extraction device to the analysis of in-house environments.

Rhythm of daily living and detection of atypical days for elderly people living alone as determined with a monitoring system.

We have developed a system for monitoring the health of elderly people living at home. Infrared and other sensor outputs are collected using a monitoring program installed on a personal computer (PC) in the home at a sampling rate of 1 Hz. Once each day, the data are transferred to a server through the Internet using a cable television (TV) connection. An elderly subject was monitored for a 12-day baseline period and completed a daily questionnaire about her activities. This enabled us to identify the rhythm of daily living (sleeping, 23:00-04:59; getting up/breakfast, 05:00-08:59; indoor activities/going out, 09:00-16:59; and dinner/going to bed, 17:00-22:59) and the average outputs from the sensors in the rooms. The subject was then monitored for a further six months. By identifying sensor output counts outside the limits of mean +/- 3SD, we were able to detect atypical days. During the six-month monitoring period, 29 atypical days were detected. We suggest that the monitoring system may be effective in tele-rehabilitation.

Isocratic separation of ginsenosides by high-performance liquid chromatography on a diol column at subambient temperatures.

An improved high-performance liquid chromatographic method for separation of a number of ginsenosides has been developed. The influence of temperature (from 0 to 25 degrees C) on the retention and separation of the ginsenosides was studied by applying a binary mobile phase (acetonitrile/water, 82:18 v/v) and a diol column (LiChrospher 100 Diol). The column temperature is one of the more important parameters for the retention and separation of the components investigated. Selected thermodynamic parameters, including changes of enthalpy (deltaH degrees) and entropy (deltaS degrees), were estimated from linear van't Hoff plots, and possible retention mechanisms were discussed. Moreover, the best separation conditions were selected based on optimization criteria including maximum retention time (t(R max)), minimum resolution (R(s min)), and relative resolution product (r). Temperature regions close to 14 degrees C offered the highest selectivity and almost equal distribution of the ginsenosides peaks across the chromatogram. Under such isocratic conditions, excellent separation of chromatographic standards and selected ginseng samples was achieved in less than 16 min.

In-needle extraction device designed for gas chromatographic analysis of volatile organic compounds.

A novel in-needle extraction device has been developed for the preconcentration of gaseous organic compounds prior to the determination in gas chromatography (GC). As the extraction medium, a copolymer of methacrylic acid and ethylene glycol dimethacrylate was synthesized. Based on the results in the preliminary experiments, the desorption conditions such as desorption temperature and time have been optimized along with the evaluation of the extraction efficiency. The storage performance of the needle extraction device was also studied. The results clearly demonstrated the excellent extraction performance for typical organic solvents and also suggested the future possibility such as in the applications for the analysis of working environments.

Surface derivatization of poly(p-phenylene terephthalamide) fiber designed for novel separation and extraction media.

The surface derivatization of poly(p-phenylene terephthalamide) fiber was studied. The obtained surface-derivatized filaments were packed into a fused-silica capillary to evaluate its surface characteristics by using GC. As the stationary phase for GC the surface-derivatized fibers showed higher retention for alkanes and alkylbenzenes than that with the untreated Kevlar fiber. The improvements on the retention power and the peak shape were observed on the benzyl-modified fibrous stationary phase. The derivatized fibrous materials were also evaluated as the extraction medium in fiber-in-tube SPE, and the effect of the surface modification on the extraction power was compared to the parent fiber. The results indicated that the modified fiber possessed a higher extraction power than the untreated fiber. Based on the facts, the successful modification of the fiber surface was estimated.

High-temperature separation with polymer-coated fiber in packed capillary gas chromatography.

High-temperature gas chromatographic separation of several synthetic polymer mixtures with Dexsil-coated fiber-packed columns was studied. A bundle of heat-resistant filaments, Zylon, was longitudinally packed into a short metal capillary, followed by the conventional coating process with Dexsil 300 material. Prior to the packing process the metal capillary was deactivated by the formation of a silica layer. The typical size of the resulting column was 0.3-mm i.d., 0.5-mm o.d., 1-m length, and packed with about 170 filaments of the Dexsil-coated Zylon. The column temperature could be elevated up to 450 degrees C owing to the good thermal stability of the fiber, Dexsil coating, and metal capillary; furthermore, this allowed the separation of low-volatile compounds to be studied.

Short metal capillary columns packed with polymer-coated fibrous materials in high-temperature gas chromatography.

The high-temperature gas chromatographic (GC) separation of several semivolatile compounds is studied with a short metal capillary column packed with fibrous material, having a polydimethylsiloxane coating thereon. Taking advantage of the excellent heat-resistance of the fiber and also the combination of the surface-deactivated metal capillary, a temperature-programmed separation up to 450 degrees C is successfully demonstrated for the separation of polymer standard samples. The average molecular weight of the commercially-available polymer standard samples for size exclusion chromatography (SEC) is estimated by high-temperature GC analysis and compared with the nominal value determined by a conventional SEC method. Although a slight deviation for the number-average molecular weight is observed between the GC and SEC analysis, the data for the weight-average molecular weight shows a good agreement in these methods. The results also suggest the future possibility of the fiber-packed metal capillary as a miniaturized GC column with an increased sample loading capacity.