Noninvasive Glucose Sensing in Dielectrically Equivalent Multilayer Skin Phantoms.

The interstitial fluid of the skin contains glucose levels comparable to those of blood. Noninvasive glucose sensing by microwaves has great potential to relieve diabetics from the burden of daily blood sampling, but improving the selectivity of this method remains a challenge. This study reports a dielectrically equivalent multilayer skin phantom and provides insight into the criteria for noninvasive glucose sensing by conducting dielectric analysis. The skin phantom was a hydrogel composed of gelatin, glucose, sodium chloride, and water covered by paraffin-impregnated paper. Investigations conducted on a wide range of component concentrations revealed characteristic relative permittivity and dielectric loss determined by the amount of electrolyte and solution that was independent of the amount of glucose. Since the microwave response due to glucose tends to be buried in noise, we developed a flowchart that first identifies the amounts of electrolytes and proteins, which are the major components other than glucose, and then quantifies the remaining glucose content. This noninvasive glucose sensing method would not be limited to the medical healthcare field; it could potentially be used in food manufacturing processes, livestock farming, and plant cultivation management.

Thermally Degradable Inductors with Water-Resistant Metal Leaf/Oleogel Wires and Gelatin/Chitosan Hydrogel Films.

Ingestible electronics monitor biometric information from outside the body. Making them with harmless or digestible materials will contribute to further reducing the burden on the patient's oral intake. Here, considering that the inductive part plays an important role in communications, we demonstrate a degradable inductor fabricated with harmless substances. Such a transient component must meet conflicting requirements for both operation and disassembly. Therefore, we integrated a substrate made of gelatin, a thermally degradable material, and a precision coil pattern made of edible gold or silver leaf. However, gelatin itself lost its initial shape easily due to quick sol-gel changes in physiological conditions. Thus, we managed the gelatin's thermal responsiveness by using a tangle of gelatin/chitosan gel networks and genipin, an organic cross-linking agent, and gained insights into the criteria for developing transient devices with thermo-degradability. In addition, to compensate for the lack of water resistance and low conductivity of thin metal foils, we propose a laminated structure with oleogel (beeswax/olive oil). LCR resonance circuits, by connecting a commercial capacitor to the coil, worked wirelessly in the megahertz band and gradually degraded in a warm-water environment. The presented organic electronics will contribute to the future development of transient wireless communications for implantable and ingestible medical devices or environmental sensors with natural and harmless ingredients.

Thermoresponsive Gelatin/Chitosan Hydrogel Films for a Degradable Capacitor.

Ingestible electronic devices are tools for exploring the condition of the gastrointestinal tract and adjacent organs without a burden on the patients. Making them safe requires that they be fabricated with harmless materials. In this study, we developed a capacitor using food materials for a wireless sensing component. As a safer approach, gelatin, an ingredient responsive to external stimuli, was selected as a substrate for deforming the device at the desired time. Gelatin experiences sol-gel changes near body temperature; however, it is instantly dissolved and is not suitable for long-term use in the body. Thus, to maintain its thermal responsiveness, we used a tangle of gel networks created by mixing gelatin and chitosan without cross-linking agents. Our search for the appropriate gel mixing ratio provided insights into the criteria for achieving slow sol-gel changes and how to improve the thermal durability. We transferred a sputtered gold film onto the gel films to produce electrodes and then made a capacitor by sandwiching a naturally dried sodium polyacrylate film between the electrodes. The resonance frequency measurement of RLC circuits in combination with commercial plane coils showed that the capacitor worked in the megahertz band and that it collapsed when immersed in hot water. Gastric acid detection was also achieved with this capacitor. This electronic part will contribute to the development of implanted or ingestible medical devices and a wide range of environmental sensors composed of natural ingredients.

Coexistence of Kosmotropic and Chaotropic Impacts of Urea on Water As Revealed by Terahertz Spectroscopy.

Whether urea can serve as a kosmotrope or chaotrope has long been a topic of debate. In this study, broad-band THz spectroscopy (0.2-12 THz) of aqueous solutions of urea was used to characterize the hydration state and the hydrogen bond structure of water around urea. Three low-frequency vibration modes of urea were found around 2, 4, and above 12 THz. After eliminating the contribution of these modes, the "urea-vibration-free" complex dielectric constant was decomposed into the relaxation modes of bulk water and the oscillation modes of water. When hydration water is defined to be reorientationally retarded relative to bulk, our analysis revealed that the hydration number is 1.9 independent of urea concentrations up to 5 M, and this number is in close agreement with that of water constrained by strong acceptor hydrogen bonds of urea oxygen. Regarding the hydrogen bond structure, it was found that the tetrahedral-like water structure is mostly preserved (though the hydrogen bond lifetime is significantly shortened) but the population of non-hydrogen-bonded water molecules fragmented from the network is markedly increased, presumably due to urea's NH2 inversion. These experimental results point to the coexistence of apparently two contradictory aspects of urea: dynamical retardation (the kosmotropic aspect) by the -CO group and slight structural disturbance (the chaotropic aspect) by the -NH2 group.

Frequency-range optimized preprocessing methods for quantitative analysis of glucose in blood serum from broadband dielectric spectra.

This paper presents the results of combining scatter correction and spectral derivation preprocessing methods with frequency-range optimization to improve the accuracy of blood glucose concentration prediction when using a Partial Least Square Regression model. Using broadband dielectric spectroscopy, absorption spectrums in the frequency range of 500 MHz to 50 GHz were gathered from blood serums. Partial Least Square Regression models were trained using data gathered from samples of varying glucose concentrations and temperatures, and the quality of the predictions were evaluated by performing leave-one-out cross validation. Potential improvements in prediction accuracy were assessed by finding the optimal frequency ranges of dielectric absorption spectrums through iteration, in addition to treatments using common preprocessing methods. The most effective combination of preprocessing method and its corresponding characteristic frequency range was determined from validation using several samples. Finally, among all the preprocessing methods and the frequency ranges explored, performing Savitzky-Golay filtering without derivations lowered the average root mean squared error amongst all the samples from 172 mg/dL without preprocessing, to 143 mg/dL. Additionally, by focusing on a specific frequency range, the root mean squared error dropped to 80.2 mg/dL.

Characterization of the hydrogen-bond network of water around sucrose and trehalose: Microwave and terahertz spectroscopic study.

Modification of the water hydrogen bond network imposed by disaccharides is known to serve as a bioprotective agent in living organisms, though its comprehensive understanding is still yet to be reached. In this study, aiming to characterize the dynamical slowing down and destructuring effect of disaccharides, we performed broadband dielectric spectroscopy, ranging from 0.5 GHz to 12 THz, of sucrose and trehalose aqueous solutions. The destructuring effect was examined in two ways (the hydrogen bond fragmentation and disordering) and our result showed that both sucrose and trehalose exhibit an obvious destructuring effect with a similar strength, by fragmenting hydrogen bonds and distorting the tetrahedral-like structure of water. This observation strongly supports a chaotropic (structure-breaking) aspect of disaccharides on the water structure. At the same time, hydration water was found to exhibit slower dynamics and a greater reorientational cooperativity than bulk water because of the strengthened hydrogen bonds. These results lead to the conclusion that strong disaccharide-water hydrogen bonds structurally incompatible with native water-water bonds lead to the rigid but destructured hydrogen bond network around disaccharides. Another important finding in this study is that the greater dynamical slowing down of trehalose was found compared with that of sucrose, at variance with the destructuring effect where no solute dependent difference was observed. This discovery suggests that the exceptionally greater bioprotective impact especially of trehalose among disaccharides is mainly associated with the dynamical slowing down (rather than the destructuring effect).

Robust respiration rate estimation using adaptive Kalman filtering with textile ECG sensor and accelerometer.

An adaptive Kalman filter-based fusion algorithm capable of estimating respiration rate for unobtrusive respiratory monitoring is proposed. Using both signal characteristics and a priori information, the Kalman filter is adaptively optimized to improve accuracy. Furthermore, the system is able to combine the respiration-related signals extracted from a textile ECG sensor and an accelerometer to create a single robust measurement. We measured derived respiratory rates and, when compared to a reference, found root-mean-square error of 2.11 breaths-per-minute (BrPM) while lying down, 2.30 BrPM while sitting, 5.97 BrPM while walking, and 5.98 BrPM while running. These results demonstrate that the proposed system is applicable to unobtrusive monitoring for various applications.

Broadband dielectric spectroscopy of glucose aqueous solution: Analysis of the hydration state and the hydrogen bond network.

Recent studies of saccharides' peculiar anti-freezing and anti-dehydration properties point to a close association with their strong hydration capability and destructuring effect on the hydrogen bond (HB) network of bulk water. The underlying mechanisms are, however, not well understood. In this respect, examination of the complex dielectric constants of saccharide aqueous solutions, especially over a broadband frequency region, should provide interesting insights into these properties, since the dielectric responses reflect corresponding dynamics over the time scales measured. In order to do this, the complex dielectric constants of glucose solutions between 0.5 GHz and 12 THz (from the microwave to the far-infrared region) were measured. We then performed analysis procedures on this broadband spectrum by decomposing it into four Debye and two Lorentz functions, with particular attention being paid to the ß relaxation (glucose tumbling), δ relaxation (rotational polarization of the hydrated water), slow relaxation (reorientation of the HB network water), fast relaxation (rotation of the non-HB water), and intermolecular stretching vibration (hindered translation of water). On the basis of this analysis, we revealed that the hydrated water surrounding the glucose molecules exhibits a mono-modal relaxational dispersion with 2-3 times slower relaxation times than unperturbed bulk water and with a hydration number of around 20. Furthermore, other species of water with distorted tetrahedral HB water structures, as well as increases in the relative proportion of non-HB water molecules which have a faster relaxation time and are not a part of the surrounding bulk water HB network, was found in the vicinity of the glucose molecules. These clearly point to the HB destructuring effect of saccharide solutes in aqueous solution. The results, as a whole, provide a detailed picture of glucose-water and water-water interactions in the vicinity of the glucose molecules at various time scales from sub-picosecond to hundreds of picoseconds.