Fiber-Coupled Fluorescence Affinity Sensor for 3-Day in Vivo Glucose Sensing

Abstract

Background:To evaluate the feasibility of an implantable fiber-coupled fluorescence affinity sensor (FAS) for glucose monitoring in humans, we studied the acute and chronic in vivo performance in hairless rats and pigs. Methods:The implantable fiber-coupled FAS was constructed by filling a dialysis chamber made of a regenerated cellulose membrane mounted to the distal tip of an optical fiber with fluorescent chemistry based on concanavalin A. Blood sugar changes in animals were induced by injections of insulin and dextrose. Determination of interstitial glucose concentrations in skin tissue was facilitated by measuring the fluorescence response of the FAS. Results:The acute in vivo response of the fiber-coupled FAS exhibited good correlation coefficients (>0.77) with blood sugar changes and minimal lag times (2-10 min) after 2 hours of sensor implantation. Equilibrium of the sensor signal with interstitial fluid was required less than 60 min after implantation. For both rats and pigs, chronic response of the FAS to blood sugar modulations measured during the third day of implantation successfully demonstrated proof-of-concept for short-term glucose monitoring. A slight decrease in sensitivity after 3 days in the small animal model was assumed to be caused by excessive mechanical forces on the implanted device because of high animal motility. Conclusions:Overall, the chronic in vivo performance of the FAS in two different animal models over 3 days was clinically acceptable and comparable to other continuous glucose monitoring platforms. The major benefit of the FAS is the absence of "autodestructive" side products and any device-related warm-up time after sensor reconnection. Technol 2007;3:384-393 Journal of Diabetes Science and Technology J Diabetes Sci

Polymer optical fiber compound parabolic concentrator tip for enhanced coupling efficiency for fluorescence based glucose sensors

“…For these glucose sensors, plane cut fiber tips have been used. In [10] it has been suggested to reduce the input power, in order to minimize the sensor drift for accurate and continuous glucose measurements. However, one limitation of the FRET based sensors is typically the low intensity of the detected fluorescence, which leads to a low signal-to-noise ratio [11].…”

“…FRET based polymer optical fiber (POF) sensors have been used for continuous in-vivo glucose sensing before [2,10]. For these glucose sensors, plane cut fiber tips have been used.…”

Blood Glucose Self-Monitoring with a Long-Term Subconjunctival Glucose Sensor

“…[8][9][10][11] Since then, the Con A competitive assay has been used in viscosimetric affinity assays, 12,13 glucose sensitive hydrogels, 14,15 and in various fluorescence-based assays. [16][17][18][19][20][21][22][23][24][25] Our group has developed a long-term BG monitoring system based on the fluorescence resonance energy transfer competitive binding assay of Con A and dextran. The system consists of an ocular mini implant (OMI) placed under the bulbar conjunctiva of the patient's eye and a handheld fluorescence photometer that reads out the sensor signal from the implant and translates it to a BG reading.…”

A Human Pilot Study of the Fluorescence Affinity Sensor for Continuous Glucose Monitoring in Diabetes

“…Therefore, various groups have developed novel glucose-sensing schemes that are not hampered by those shortcomings. These promising technologies are relying not on signal generation as a result of an enzymatic reaction, but on an affinity-type binding reaction between a glucose-specific receptor (e.g., boronate group), [15][16][17] a lectin [concanavalin A (ConA)], [18][19][20][21][22][23] or an apoprotein (apo-GOx, an inactive form of glucose oxidase) 24 and glucose itself or a glucose analog.…”