Yun Jung Heo

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.

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 highly-sensitive, 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.

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system. These ultrathin and ultralight microneedle sensor arrays continuously and precisely monitored glucose concentration in the interstitial fluid with minimally invasive, pain-free, wound-free, and skin inflammation-free outcomes at various locations and thicknesses of the skin. Bioresorbability in the body without a need for device removal after use was a key characteristic of the microneedle glucose sensor. We demonstrated the potential long-term use of the bioresorbable device by applying the tether-free CGM system, thus confirming the successful detection of glucose levels based on changes in fluorescence intensity. In addition, this microneedle glucose sensor with a user-friendly designed home diagnosis system using mobile applications and portable accessories offers an advance in CGM and its applicability to other bioresorbable, wearable, and implantable monitoring device technology.

Diabetes can strike at any age, from childhood to adulthood, and lasts a lifetime. Thus, it is important to find ways to increase the quality of life for diabetic patients through intensive, continuous care of blood glucose concentrations. Glucose biosensors that are implanted under the skin are promising for continuous glucose monitoring because they can constantly read blood glucose concentrations and signal a warning in case of hypo- or hyperglycemia. The demand for subcutaneous glucose biosensors has led to the development of many glucose-sensing principles and sensor designs. This Review covers the effort to develop subcutaneous glucose biosensors, including the glucose-sensing principles, and discusses their current status for in vivo monitoring. In addition, the Review examines the future prospects for intensive diabetes care.

Hyun Kim, Koo Young Jung, Sun Pyo Kim, Sun Hyu Kim, Hyun Noh, Hye Young Jang, Han Deok Yoon, Yun Jung Heo, Hyun Ho Ryu, Tae oh Jeong, Yong Hwang, Jung Min Ju, Myeong Don Joo, Sang Kyoon Han, Kwang Won Cho, Ki Hoon Choi, Joon Min Park, Hyun Min Jung, Soo Bock Lee, Yeon Young Kyong, Ji Yeong Ryu, Woo Chan Jeon, Ji Yun Ahn, Jang Young Lee, Ho Jin Ji, Tae Hun Lee, Oh Hyun Kim, Youg Sung Cha, Kyung Chul Cha, Kang Hyun Lee, Sung Oh Hwang