The use of fluorescence-based sensors holds great promise for continuous glucose monitoring (CGM) in vivo, allowing wireless transdermal transmission and long-lasting functionality in vivo. The ability to monitor glucose concentrations in vivo over the long term enables the sensors to be implanted and replaced less often, thereby bringing CGM closer to practical implementation. However, the full potential of long-term in vivo glucose monitoring has yet to be realized because current fluorescence-based sensors cannot remain at an implantation site and respond to blood glucose concentrations over an extended period. Here, we present a long-term in vivo glucose monitoring method using glucose-responsive fluorescent hydrogel fibers. We fabricated glucose-responsive fluorescent hydrogels in a fibrous structure because this structure enables the sensors to remain at the implantation site for a long period. Moreover, these fibers allow easy control of the amount of fluorescent sensors implanted, simply by cutting the fibers to the desired length, and facilitate sensor removal from the implantation site after use. We found that the polyethylene glycol (PEG)-bonded polyacrylamide (PAM) hydrogel fibers reduced inflammation compared with PAM hydrogel fibers, transdermally glowed, and continuously responded to blood glucose concentration changes for up to 140 days, showing their potential application for long-term in vivo continuous glucose monitoring.glucose-responsive fluorescence | long-lasting implantable sensor | biocompatible interface | implantable glucose sensor | diabetes mellitus I n vivo glucose monitoring allows continuous glucose monitoring (CGM) and facilitates intensive control of blood glucose concentrations in diabetic patients. Long-lasting implantable sensors can reduce the frequency of implantation and replacement, resulting in long-term in vivo glucose monitoring with less effort by patients and less tissue damage. For decades, implantable sensors for long-term use have been developed using enzyme electrodes. However, these methods have several drawbacks for long-term use because these enzyme based sensors are insufficiently stable in vivo (1), they are poorly accurate in low glucose concentrations (2), and their activity is oxygen-dependent (3). In contrast, glucose-responsive fluorescence is a promising approach that maintains long-lasting functionality in vivo due to its enzyme-free and reversible reaction (4-9). We recently developed fluorescent hydrogel microbeads that are transdermally detectable, injectable, minimally invasive, and biocompatible (10). To bring this technology closer to long-term application, the fluorescent hydrogel sensors need to remain at the implantation site for a long period (over 3 mo) and be easily removable after use; despite their great potential for continuous glucose monitoring, the microbeads were not suitable for long-term monitoring in vivo because they dispersed from the implantation site and were difficult to remove. In addition, the biointerface of the fluoresce...

Fluorescent microbeads hold great promise for in vivo continuous glucose monitoring with wireless transdermal transmission and long-lasting activity. The full potential of fluorescent microbeads has yet to be realized due to insufficient intensity for transdermal transmission and material toxicity. This paper illustrates the highlysensitive, biostable, long-lasting, and injectable fluorescent microbeads for in vivo continuous glucose monitoring. We synthesized a fluorescent monomer composed of glucose-recognition sites, a fluorogenic site, spacers, and polymerization sites. The spacers are designed to be long and hydrophilic for increasing opportunities to bind glucose molecules; consequently, the fluorescent monomers enable high-intensive responsiveness to glucose. We then fabricated injectable-sized fluorescent polyacrylamide hydrogel beads with high uniformity and high throughput. We found that our fluorescent beads provide sufficient intensity to transdermally monitor glucose concentrations in vivo. The fluorescence intensity successfully traced the blood glucose concentration fluctuation, indicating our method has potential uses in highly-sensitive and minimally invasive continuous blood glucose monitoring.iabetes is a global pandemic affecting over 200 million people (1, 2). Maintaining normal blood glucose concentrations is crucial for preventing diabetic complications in the heart, kidney, retina, and neural system (3-6). The fingertip prick method for collecting a blood sample is used at present to accurately analyze blood glucose concentrations. However, the method provides intermittent information concerning glucose concentrations, which is not suitable to predict the trend of blood glucose change. In contrast, continuous glucose monitoring (CGM) allows diabetic patients to effortlessly recognize changes in blood glucose concentrations and signals a warning in the case of hypoand hyperglycemia patients; even when diabetic patients are sleeping (7,8).Fully-implantable glucose sensors, embedded in the body, are ideal for CGM. Previously, microdialysis and enzyme-tipped catheters have been developed as fully-implantable glucose sensors for CGM. Although these sensors are capable of providing the sequential information of blood glucose concentrations to diabetic patients, they need to have external links for continuously collecting samples or transmitting signals; thereby these methods cause discomfort and the risk of infection. Recently, an optical method using fluorescent beads (9-12) was proposed for CGM. This method provides wireless transmission through the skin, and long-lasting activity in vivo compared to enzymebased methods (13-16) that require an electrochemical reaction. However, fully-implantable glucose sensors based on the fluorescent principle have not yet been developed mainly due to the insufficient fluorescent intensity required for transdermal detection and the toxicity of the material (17).Here, we developed the highly-sensitive, biostable, longlasting, and injectable fluorescent micro...

In this study, we demonstrate a novel method for preparing crystallized mesoporous titania by using a low-temperature synthesis technique in the presence of cationic surfactant. XRD patterns showed that the titania particles obtained had both hexagonal structure and a wall with anatase crystalline structure. Transmission electron microscopy (TEM) observation and corresponding electron diffraction pattern confirmed that the calcined particles are crystallized mesoporous titania.

Core/shell-type titania nanocapsules containing a single Ag nanoparticle were prepared. Ag nanoparticles were prepared using the reduction of silver nitrate with hydrazine in the presence of cetyltrimethylammonium bromide (CTAB) as protective agent. The sol-gel reaction of titanium tetraisopropoxide (TTIP) was used to prepare core/shell-type titania nanocapsules with CTAB-coated Ag nanoparticles as the core. TEM observations revealed that the size of the core (Ag particle) and the thickness of the shell (titania) of the core/shell particles obtained are about 10 nm and 5-10 nm, respectively. In addition, the nanocapsules were found to be dispersed in the medium as individual particles without aggregation. Moreover, titania coating caused the surface plasmon absorption of Ag nanoparticles to shift toward the longer wavelength side.

Self-assembly enables exquisite control over the structures of various materials such as ultrathin organic films, [1][2][3][4] polymer films, [5][6][7] and inorganic nanoparticle assemblies. [8] Organic molecules are particularly suited for exploiting self-assembly because of the controllability of their molecular properties and intermolecular interactions using molecular design. Lateral patterning of organic materials has been performed using both top-down [6,9] and bottom-up [1][2][3][4][5]7] methods. However, construction of controllable nanostructures consisting of small organic molecules is difficult using bottom-up methods. In this Communication, we show that by using self-assembly, ultrathin films of small organic molecules are patterned with nanostructures, the sizes of which are controlled by adjusting intermolecular interactions. We demonstrate the formation of nanowires of controllable widths in phase-separated mixed monolayers. Organic and inorganic materials can be confined on the templates fabricated from phase-separated monolayers. Further, we report on the formation of spirals in threecomponent monolayers. We used the Langmuir-Blodgett (LB) technique for the fabrication of controlled nanostructures. Phase separation often occurs in mixed-Langmuir and LB films, the structures of which are governed by two competing interactions of line tension and dipole-dipole interactions. [1,3,10] Line tension favors the formation of large circular domains. Dipole-dipole interactions in monolayers is repulsive because each molecule is aligned in a parallel manner. Systematic variations in one of the interactions without changing the other should provide us with a means to control the phase-separated structures in monolayers. Along this line, we examined the phase-separated structures of two-component mixed LB films of fatty acid C k H 2k+1 COOH (HkA) and hybrid carboxylic acid C m F 2m+1 C n H 2n COOH (FmHnA), with systematic variations in k, m, and n. Dipoles that contribute dominantly to the phase-separated structures are those located at both ends of the molecules: [11] those due to methyl and carboxylic groups of HkA and those due to perfluoromethyl and carboxylic groups of FmHnA. Variations in alkyl and perfluoroalkyl chain lengths should not significantly affect the vertical component of the above dipoles as long as the molecular arrangement remains unchanged. Under these conditions, variations in the structures of the hydrophobic moieties of the molecules significantly affect only the line tension and not the dipole-dipole interactions. Figure 1 shows the change in the phase-separated structures of two-component LB films of H17A and FmH8A. Friction force microscopic observations show that the high and low parts consist of H17A and FmH8A, respectively. Circular domains of micrometer length scale form when m is small, showing the dominant role of line tension. In contrast, nanowires form when m is large, indicating the effect of dipole-dipole interactions.

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Mesoporous titania particles having anatase-type crystalline wall were prepared using a low-temperature crystallization technique. Crystalline mesoporous titania was obtained through the sol−gel process of titanium oxysulfate sulfuric acid hydrate (TiOSO4·xH2SO4·xH2O) at 333 K in the presence of cetyltrimethylammonium bromide (C16TAB), a cationic surfactant. The mesoporous titania with hexagonal structure was formed according to the following mechanism. Nuclei of ultrafine titanium hydroxide oxide (TiO(OH)2) were formed from TiOSO4 on the periphery of the surface of cationic C16TAB micelles at the primary stage of sol−gel reaction. Then, heat treatment at 333 K induced the transformation of the particle wall from TiO(OH)2 to anatase nanocrystal, which resulted in the formation of mesoporous titania with a crystalline wall. Moreover, the presence of bromide ion (Br-), the counterion of C16TAB, was shown to suppress the collapse of mesostructure by retarding the transition from anatase to rutile.

Phase separation often occurs in mixed Langmuir-Blodgett (LB) films. Usually circular domains at the micrometer length scale form in the LB films. The size and shape of the domains are governed by a compromise between two competing interactions of line tension and dipole-dipole interaction. An attempt was made to control the line tension by varying systematically the hydrophobic moieties of the film-forming molecules. Phase-separated structures of two-component mixed LB films of fatty acid [C(k)H(2k+1)COOH (HkA)] and hybrid carboxylic acid [C(m)F(2m+1)C(n)H(2n)COOH (FmHnA)] were investigated. IR spectra of the mixed LB films of H17A and F8H10A revealed that the alkyl chains were in an all-trans conformation and that the molecular orientation remained unchanged when the two components were mixed. Nanowires formed in the mixed LB films of HkA and F8H10A. The width of the nanowires increased with an increase in k. Domain size and shape in the mixed LB films of H17A and FmHnA depended strongly on the values of m and n. Circular domains at the micrometer length scale formed in the region m + n < 16. In contrast, domains at the nanometer length scale formed in the region m + n > or = 16 except for F6H10A. These results were explained by using a lattice model that considers the effect of the hydrophobic moieties of fatty acid and hybrid carboxylic acid on the line tension.