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.

Data Processing of SPR Curve Data to Maximize the Extraction of Changes in Electrochemical SPR Measurements.

We developed a novel measuring and data-processing method for performing electrochemical surface plasmon resonance (EC-SPR) on sensor surfaces for which detecting a specific SPR angle is difficult, such as a polymer having a non-uniform thickness with coloration. SPR measurements are used in medicine and basic research as an analytical method capable of molecular detection without labeling. However, SPR is not good for detecting small molecules with small refractive index changes. The proposed EC-SPR, which combines SPR measurements with an electrochemical reaction, makes it possible to measure small molecules without increasing the number of measurement steps. A drawback of EC-SPR is that it is difficult to detect a specific SPR angle on electron mediators, and it was found that it may not be possible to capture all the features produced. The novel method we describe here is different from the conventional one in which a specific SPR angle is obtained from an SPR curve; rather, it processes the SPR curve itself and can efficiently aggregate the feature displacements in the SPR curves that are dispersed through multiple angles. As an application, we used our method to detect small concentrations of H2O2 (LOD 0.7 µM) and glutamate (LOD 5 µM).

Microfluidic Devices Controlled by Machine Learning with Failure Experiments.

A critical microchannel technique is to isolate specific objects, such as cells, in a biological solution. Generally, this particle sorting is achieved by designing a microfluidic device and tuning its control values; however, unpredictable motions of the particle mixture make this approach time-consuming and labor intensive. Here, we show that microfluidic control with reinforced learning characterized by utilizing failure results can maximize the training effect with limited data. This method uses microscopic images of the separation process, including failed conditions (inappropriate flow speeds or dilution rates of biological samples), and insights for efficient learning are provided by setting gradient rewards according to the degree of failure. Once learning is performed in this manner, the optimal separating condition for other related samples can be automatically found. Failed experiments are not wasteful; they increase training data and make it easier to reach correct answers. This device control could be useful in automatic synthetic chemistry, biomedical analysis, and microfabrication robotics.

Designing a multilayer film via machine learning of scientific literature.

Scientists who design chemical substances often use materials informatics (MI), a data-driven approach with either computer simulation or artificial intelligence (AI). MI is a valuable technique, but applying it to layered structures is difficult. Most of the proposed computer-aided material search techniques use atomic or molecular simulations, which are limited to small areas. Some AI approaches have planned layered structures, but they require a physical theory or abundant experimental results. There is no universal design tool for multilayer films in MI. Here, we show a multilayer film can be designed through machine learning (ML) of experimental procedures extracted from chemical-coating articles. We converted material names according to International Union of Pure and Applied Chemistry rules and stored them in databases for each fabrication step without any physicochemical theory. Compared with experimental results which depend on authors, experimental protocol is superiority at almost unified and less data loss. Connecting scientific knowledge through ML enables us to predict untrained film structures. This suggests that AI imitates research activity, which is normally inspired by other scientific achievements and can thus be used as a general design technique.

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.

Direct Measurement of Near-Wall Molecular Transport Rate in a Microchannel and Its Dependence on Diffusivity.

Solute transport in a narrow space is the most elemental process in chromatography and biological pattern formation. However, the observation of such transport has been quite difficult, and theoretical investigations have therefore preponderated. Here, using a space- and time-resolved surface plasmon resonance (SPR) method, we measured the nanoscale near-wall (next to the wall) transport rate in a narrow channel after a solution and its solvent had come into contact. By combining the SPR method with a capillary injection method, which enables two solution plugs to flow immediately after they have made contact, we were able to measure the solute concentration evolution at the channel wall. We tested three combinations of two plugs of solution-water-glucose, sodium chloride-water, and glucose-sodium chloride-and succeeded in measuring diffusion-coefficient-dependent changes in the concentration of solute flowing through a rectangular microchannel in less than 0.4 s. A numerical analysis of this system revealed the acceleration of the solute/solution boundary moving on the wall and its deceleration at the center of the channel cross section. The observed experimental transport rate agreed with the numerical result quantitatively. These results show that the solute transport followed a laminar flow with a no-slip model and that the molecules were transported in the order of their diffusivity. In the third combination, when the two solutions made contact and started flowing, the interdiffusion of the solutes resulted in temporal concentrations lower than either of the solutions before contact, which indicated that the contact between the two solutions quickly led to separation by the advection-diffusion processes. We found that such a concentration profile could actually be measured. Our techniques are simple and applicable to a wide range of molecules; the method opens the way to direct observation of the space-time near-wall solute transport process and can be used for the rapid determination of diffusivity.

A reliable aptamer array prepared by repeating inkjet-spotting toward on-site measurement.

A preparation protocol is proposed for a reliable aptamer array utilizing an ink-jet spotter. We accumulated streptavidin and biotinylated-aptamer in this order on a biotinylated-polyethylene glycol-coated gold substrate to prepare an aptamer array. The aptamer array was prepared with an alternate spotting structure where each aptamer spot was placed between reference spots formed with blocking solution thus suppressing contamination from neighboring spots during the blocking and washing processes. Four aptamer spots were prepared in a small area of 1×4.8mm(2) with five reference spots made of blocking solution. We evaluated the thrombin binding ability of the spotted aptamer array using a multi-analysis surface plasmon resonance sensor. We prepared a disposable capillary-driven flow chip designed for on-site measurement (Miura et al., 2010) with our aptamer array and detected thrombin from phosphate-buffered saline at concentrations of 50ngmL(-1) and 1µgmL(-1) (equivalent to 1.35 and 27nM, respectively). A correlation was observed between the refractive index shift and thrombin concentration. This implies that our array preparation protocol meets the requirement for the preparation of a one-time-use chip for on-site measurement.

Floating chip mounting system driven by repulsive force of permanent magnets for multiple on-site SPR immunoassay measurements.

We have developed a measurement chip installation/removal mechanism for a surface plasmon resonance (SPR) immunoassay analysis instrument designed for frequent testing, which requires a rapid and easy technique for changing chips. The key components of the mechanism are refractive index matching gel coated on the rear of the SPR chip and a float that presses the chip down. The refractive index matching gel made it possible to optically couple the chip and the prism of the SPR instrument easily via elastic deformation with no air bubbles. The float has an autonomous attitude control function that keeps the chip parallel in relation to the SPR instrument by employing the repulsive force of permanent magnets between the float and a float guide located in the SPR instrument. This function is realized by balancing the upward elastic force of the gel and the downward force of the float, which experiences a leveling force from the float guide. This system makes it possible to start an SPR measurement immediately after chip installation and to remove the chip immediately after the measurement with a simple and easy method that does not require any fine adjustment. Our sensor chip, which we installed using this mounting system, successfully performed an immunoassay measurement on a model antigen (spiked human-IgG) in a model real sample (non-homogenized milk) that included many kinds of interfering foreign substances without any sample pre-treatment. The ease of the chip installation/removal operation and simple measurement procedure are suitable for frequent on-site agricultural, environmental and medical testing.

Cooperative suction by vertical capillary array pump for controlling flow profiles of microfluidic sensor chips.

A passive pump consisting of integrated vertical capillaries has been developed for a microfluidic chip as an useful component with an excellent flow volume and flow rate. A fluidic chip built into a passive pump was used by connecting the bottoms of all the capillaries to a top surface consisting of a thin layer channel in the microfluidic chip where the thin layer channel depth was smaller than the capillary radius. As a result the vertical capillaries drew fluid cooperatively rather than independently, thus exerting the maximum suction efficiency at every instance. This meant that a flow rate was realized that exhibited little variation and without any external power or operation. A microfluidic chip built into this passive pump had the ability to achieve a quasi-steady rather than a rapidly decreasing flow rate, which is a universal flow characteristic in an ordinary capillary.

Passive fluidic chip composed of integrated vertical capillary tubes developed for on-site SPR immunoassay analysis targeting real samples.

We have successfully developed a surface plasmon resonance (SPR) measurement system for the on-site immunoassay of real samples. The system is composed of a portable SPR instrument (290 mm(W) × 160 mm(D) × 120 mm(H)) and a microfluidic immunoassay chip (16 mm(W) × 16 mm(D) × 4 mm(H)) that needs no external pump system. An integrated vertical capillary tube functions as a large volume (150 µL) passive pump and a waste reservoir that has sufficient capacity for several refill operations. An immunoassay was carried out that employed the direct injection of a buffer and a test sample in sequence into a microfluidic chip that included 9 antibody bands and 10 reference reagent bands immobilized in the flow channel. By subtracting a reliable averaged reference sensorgram from the antibody, we effectively reduced the influence of the non-specific binding, and then our chip successfully detected the specific binding of spiked IgG in non-homogeneous milk. IgG is a model antigen that is certain not to be present in non-homogeneous milk, and non-homogeneous milk is a model of real sample that includes many interfering foreign substances that induce non-specific binding. The direct injection of a real sample with no pretreatment enabled us to complete the entire immunoassay in several minutes. This ease of operation and short measuring time are acceptable for on-site agricultural, environmental and medical testing.

Effects of surface water on gas sorption capacities of gravimetric sensing layers analyzed by molecular descriptors of organic adsorbates.

The gas sorption capacities of sputtered carbonaceous films are evaluated with quartz crystal resonators. These films are sensitive to 20 ppm organic vapors and exhibit structure-dependent responses. Films derived from synthetic polymers are hydrophobic, whereas films derived from biomaterials are amphiphilic or hydrophilic. Polyethylene (PE) film has an extremely high sorption capacity for a wide range of vapors. Transient sorption responses are investigated using a humidified carrier by employing carboxylic acid esters, whose aliphatic groups are systematically changed. Small esters with a higher affinity to water induce negative U-shaped responses from amphiphilic films derived from biomaterials. On the other hand, polymeric films exhibit positive exponential response curves. Even if the concentrations are decreased, the response intensities are enhanced with the incremental expansion of carbon chains of aliphatic groups. Only fluoropolymer film shows the opposite tendency. The modeling of quantitative structure property relationships has indicated that the sorption capacities of the PE film to the carboxylic acid esters are fundamentally governed by electrostatic interactions. The intermolecular attractive forces are basically attributable to interactions between the positively polarized sites in esters and the negatively polarized/charged sites in PE film.

Chirality emergence in thin solid films of amino acids by polarized light from synchrotron radiation and free electron laser.

One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of "chiral impulse" as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds.

Discriminative detection of volatile sulfur compound mixtures with a plasma-polymerized film-based sensor array installed in a humidity-control system.

We demonstrated the discrimination of volatile sulfur compound mixtures with different mixing ratios by using an array of the plasma-polymerized film (PPF)-coated quartz crystal resonators. The PPF sensor array, which contains PPFs prepared from amino acids and synthetic polymers, exhibited different response patterns to mono or mixed volatile sulfur compounds (VSCs) (hydrogen sulfide and methanethiol) under a dry environment. The sensor array was installed in a desktop-size relative humidity controller. The relative humidity and temperature conditions of the sample flow to the sensor cell were equalized to those of the inner atmosphere of the sensor cell based on the concept of the two-separate-temperatures method. In this way, the baseline drift of PPF sensor response caused by the introduction of a highly humid sample was successfully suppressed. We compared the sensor array responses under the controlled humidity conditions. Presorption of water molecules by PPFs caused a decrease of sensor sensitivity, but the films still had the ability to discriminate sub-ppmv VSC mixtures having 6:1, 1:1, and 1:6 mixture ratios of hydrogen sulfide and methanethiol.

Aroma sensing and indoor air monitoring by quartz crystal resonators with sensory films prepared by sputtering of biomaterials and sintered polymers.

Thickness shear mode quartz-crystal resonator coated with plasma polymer films (PPFs) produced by radio-frequency sputtering of biomaterials and synthetic polymers were examined with respect to their abilities to continuously monitor indoor air. We confirmed the sensory capabilities of an array of PPF sensors to aromas emitted from essential oils at concentrations as low as the detection threshold of human olfaction. Changes in humidity induced a drift in the response curves of PPF sensors. On the contrary, volatile compounds exhibited pulse signals. The pulse signals of a D-phenylalanine sensor and a polyethylene sensor were synchronous, but the direction of the peaks was inverted in most cases. Compared with a photo-ionization detector sensor, the PPF sensors were able to detect subtle changes in the concentrations of volatile compounds in indoor air.