In Vivo, Transcutaneous Glucose Sensing Using Surface-Enhanced Spatially Offset Raman Spectroscopy: Multiple Rats, Improved Hypoglycemic Accuracy, Low Incident Power, and Continuous Monitoring for Greater than 17 Days

Abstract

This paper presents the latest progress on quantitative, in vivo, transcutaneous glucose sensing using surface enhanced spatially offset Raman spectroscopy (SESORS). Silver film over nanosphere (AgFON) surfaces were functionalized with a mixed self-assembled monolayer (SAM) and implanted subcutaneously in Sprague-Dawley rats. The glucose concentration was monitored in the interstitial fluid of six separate rats. The results demonstrated excellent accuracy and consistency. Remarkably, the root mean square error of calibration (RMSEC) (3.6 mg/dL) and the root mean square error of prediction (RMSEP) (13.7 mg/dL) for low glucose concentration (< 80 mg/dL) is lower than the current International Organization Standard (ISO/DIS 15197) requirements. None of the commercially available glucose sensing techniques can achieve enough accuracy during hypoglycemic episodes. Additionally, our sensor demonstrated functionality up 17 days after implantation, including 12 days under the laser safety level for human skin exposure with only one time calibration. Therefore, our SERS based sensor shows promise for the challenge of reliable continuous glucose sensing systems for optimal glycemic control.

Surface enhanced Raman spectroscopy (SERS): Potential applications for disease detection and treatment

“…[83] The device was found to actively work over 17 days and more importantly the authors reported that between days 6 and 17, the glucose levels measured were found to lie within the clinically relevant levels. [83] This elegant and sophisticated example is a significant step forward in the development of a method by which diabetes sufferers could monitor and control their condition more accurately. [83] A similar format was also used to monitor lactate quantitatively.…”

“…[60] Later work by the same group has strived to further develop this method for in vivo sensing. [81][82][83] In the initial stages the sensors (as described above) were implanted into animal models and the glucose levels were successfully measured via SERS and surface enhanced spatially offset Raman spectroscopy (SESORS) respectively. [81][82][83].…”

“…[83] This elegant and sophisticated example is a significant step forward in the development of a method by which diabetes sufferers could monitor and control their condition more accurately. [83] A similar format was also used to monitor lactate quantitatively. [61] Variations in lactate levels can be indicative of trauma in a number of medical conditions and as with glucose monitoring the ability to measure lactate in real time would further improve the clinical care offered to patients suffering from a range of conditions.…”

Recent advances in the development of Raman spectroscopy for deep non‐invasive medical diagnosis

“…The glucose was successfully monitored in the interstitial fluid using SORS at clinically relevant levels. This pioneering experiment was subsequently extended by demonstrating a viability of monitoring of glucose levels in multiple rats (6) over a 17 day period with improved glycaemic index accuracy [73]. The rootmean-square error of calibration (RMSEC) (3.6 mg/ dL) and the root-mean-square error of prediction (RMSEP) (13.7 mg/dL) for low glucose concentration (< 80 mg/dL) was lower than the current International Organization Standard (ISO/DIS 15197) requirements.…”

Surface Enhanced Raman Scattering

“…In vivo transcutaneous SESORS glucose calibration and validation data sets on rat for a 5-day period. 22) Measurements from day 1 and 2 (blue ◆) were used for calibration sets. Measurements from day 3 (red •) and 4 (red ○) and 5 (red＋) were used for validation sets.…”