A Quantitative Look Inside the Body: Minimally Invasive Infrared Analysis in Vivo

Abstract

Today's minimally invasive biosensors are often based on chemical reagents and suffer from, e.g., oxygen dependence, toxic reaction products, excess analyte consumption, and/or degradation of the reagents. Here, we show the first successful analyte quantification by means of a minimally invasive sensor in vivo, which does not use chemical reactions. The concentration of glucose is determined continuously in vivo using transcutaneous, fiber-based mid-infrared laser spectroscopy. When comparing the infrared data measured in vivo with the 127 reference readings of glucose obtained in vitro, an overall standard deviation of 17.5% and a median of the absolute values of the relative deviations of 11.0% are achieved. The encouraging results open up the path toward a reagent-free long-term implant for the continuous surveillance of metabolites. In addition, the high sampling rate facilitates important research in body metabolism as well as its application outside the field of medicine such as real-time analyte sensing during fermentation.

Quantum cascade lasers (QCLs) in biomedical spectroscopy

“…After multiple refinement steps of the method, [203][204][205] Vrančić et al presented a minimally invasive fiber-based sensor for continuous in vivo glucose monitoring. 206 Here, a pulsed, nontunable laser operated at 1030 cm À1 was used with a pyroelectric detector. The silver halide fiber with a 20 mm gap was implanted in a rat's neck and changes of the glucose level were continuously monitored in the ISF after injections of glucose or insulin.…”

Towards a quantum cascade laser-based implant for the continuous monitoring of glucose

“…Vrancić et al [13] could increase the sensitivity to NEC values as low as 4 mg/dL using also a fiber-based sensor setup with a discrete frequency Fabry-Perot QCL and an optical path length of 30 µm. Vrancić et al [14] also performed the first in vivo experiments using this fiber-based sensor in an animal-model. With a prediction accuracy of 7 mg/dL and a sampling duration of 6 s over a period of several hours, they showed that the method is in principle well suited for in vivo use.…”

“…Besides this vast progress in the field of in vitro analytics, Vrancić et al [14] still remain the only group that investigated this method in vivo and built a basis for continuous glucose monitoring in diabetes patients. They used silver/ silver halide fibers in transmission with a microfabricated gap in the fiber to be filled by the liquid via diffusion processes.…”

Accuracy Improvement of Blood Glucose Measurement System Using Quantum Cascade Lasers

“…These researchers irradiated the human palm or wrist with an EC-QCL and measured the backscattered light using a hollow optical fiber [14] or an integrating sphere [15]. Furthermore, some groups have used photoacoustic techniques to measure glucose concentrations in the interstitial fluid of human skin [24]. The authors successfully measured glucose concentrations in the interstitial fluid of rats by using a fiber probe with small gaps that was filled with the sample material.…”