Infrared Spectroscopy with a Fiber-Coupled Quantum Cascade Laser for Attenuated Total Reflection Measurements Towards Biomedical Applications

Abstract

The development of rapid and accurate biomedical laser spectroscopy systems in the mid-infrared has been enabled by the commercial availability of external-cavity quantum cascade lasers (EC-QCLs). EC-QCLs are a preferable alternative to benchtop instruments such as Fourier transform infrared spectrometers for sensor development as they are small and have high spectral power density. They also allow for the investigation of multiple analytes due to their broad tuneability and through the use of multivariate analysis. This article presents an in vitro investigation with two fiber-coupled measurement setups based on attenuated total reflection spectroscopy and direct transmission spectroscopy for sensing. A pulsed EC-QCL (1200–900 cm−1) was used for measurements of glucose and albumin in aqueous solutions, with lactate and urea as interferents. This analyte composition was chosen as an example of a complex aqueous solution with relevance for biomedical sensors. Glucose concentrations were determined in both setup types with root-mean-square error of cross-validation (RMSECV) of less than 20 mg/dL using partial least-squares (PLS) regression. These results demonstrate accurate analyte measurements, and are promising for further development of fiber-coupled, miniaturised in vivo sensors based on mid-infrared spectroscopy.

Infrared measurements of glucose in peritoneal fluid with a tuneable quantum cascade laser

“…One option is to use a smaller single-reflection IRE with signal-enhancement, which has given good preliminary results in the same setup as used here [33]. As discussed in our earlier study [26], a commercialised QCL-based sensor will also likely require the use of a few fixed-wavelength lasers for cost and size reduction instead of a tuneable laser. Some previous QCL studies on glucose measurements have explored concentration predictions with only a few wavenumbers [34,35], which has demonstrated that this is a possible avenue for sensor development.…”

“…This prism had a surface area of 24 mm x 2.4 mm, and a height of 1.2 mm. The thickness of this prism was half of that used in our previous ATR experiments [26], and it had 11 reflections on the top surface. Hollow-core optical fibres with an inner diameter of 1 mm were used for in-and out-coupling of light.…”

“…These setups were similar to those we previously characterised and used for measurements of aqueous solutions, see Ref. [ 26 ] for further details. The full tuning range of this laser was 1200–900 cm −1 , which corresponds to 8.3–11.1 m. The EC-QCL ran in pulsed mode at a frequency of 100 kHz with 500 ns long pulses.…”

A Compact Mid-Infrared Spectroscopy System for Healthcare Applications Based on a Wavelength-Swept, Pulsed Quantum Cascade Laser

“…Although chalcogenide glass optical fiber and polycrystalline optical fiber are commercially available as types of mid-infrared optical fiber, the latter is advantageous because it does not contain toxic material prohibited from being used in biomedical applications. Various proposals for spectroscopic systems using a QCL and AgCl/AgBr polycrystalline optical fiber have been made [ 6 , 7 ]. Moreover, because of its simpler structure, a hollow optical fiber is advantageous in terms of cost and durability as an optical transmission medium for mid-infrared spectroscopy systems.…”

“…The QCL-based systems have already been applied to various biomedical applications [ 13 ] including the detection of NO gas [ 14 ], ammonia detection [ 15 ] in breath, blood glucose concentration measurement [ 7 , 16 , 17 , 18 ], and drug detection in saliva [ 19 ]. For these application systems, an external cavity-type QCL (EC-QCL) capable of wavelength sweeping is typically used.…”