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.