Mid-infrared spectroscopic characterisation of an ultra-broadband tunable EC-QCL system intended for biomedical applications

Mid-infrared spectroscopy has been successfully applied for reagent-free clinical chemistry applications. Our aim is to design a portable bed-side system for ICU patient monitoring, based on mid-infrared absorption spectra of continuously sampled body-fluids. Robust and miniature bed-side systems can be achieved with tunable external cavity quantum cascade lasers (EC-QCL). Previously, single EC-QCL modules covering a wavenumber interval up to 250 cm-1 have been utilized. However, for broader applicability in biomedical research an extended interval around the mid-infrared fingerprint region should be accessible, which is possible with at least three or four EC-QCL modules. For such purpose, a tunable ultra-broadband system (1920 - 780 cm-1, Block Engineering) has been studied with regard to its transient emission characteristics in ns time resolution during different laser pulse widths using a VERTEX 80v FTIR spectrometer with step-scan option. Furthermore, laser emission line profiles of all four incorporated EC-QCL modules have been analysed at high spectral resolution (0.08 cm-1) and beam profiles with few deviations from the TEM 00 spatial mode have been manifested. Emission line reproducibility has been tested for various wavenumbers in step tune mode. The overall accuracy of manufacturer default wavenumber setting has been found between ± 3 cm-1 compared to the FTIR spectrometer scale. With regard to an application in clinical chemistry, theoretically achievable concentration accuracies for different blood substrates based on blood plasma and dialysate spectra previously recorded by FTIRspectrometers have been estimated taking into account the now accessible extended wavenumber interval.

[1]  M. W. George,et al.  Probing Organometallic Reactions by Time-Resolved Infrared Spectroscopy in Solution and in the Solid State Using Quantum Cascade Lasers , 2015, Applied spectroscopy.

[2]  Roman Hovorka,et al.  A Stepwise Approach toward Closed-Loop Blood Glucose Control for Intensive Care Unit Patients: Results from a Feasibility Study in Type 1 Diabetic Subjects Using Vascular Microdialysis with Infrared Spectrometry and a Model Predictive Control Algorithm , 2011, Journal of diabetes science and technology.

[3]  H. M. Heise,et al.  Multicomponent Assay for Blood Substrates in Human Plasma by Mid-Infrared Spectroscopy and its Evaluation for Clinical Analysis , 1994 .

[4]  Salvador Garrigues,et al.  Infrared-based quantification of clinical parameters , 2014 .

[5]  Timothy Day,et al.  Progress towards compact broadly tunable laser modules for high-resolution mid-IR spectroscopy and commercial applications , 2012, OPTO.

[6]  Kexin Xu,et al.  Continuous glucose determination using fiber-based tunable mid-infrared laser spectroscopy , 2014 .

[7]  Christoph Herwig,et al.  Reagent-free monitoring of multiple clinically relevant parameters in human blood plasma using a mid-infrared quantum cascade laser based sensor system. , 2013, The Analyst.

[8]  Thorsten Vahlsing,et al.  Influence of spectral bandwidth limitations of tuneable external-cavity based quantum cascade laser systems for clinical biofluid analysis , 2014, Photonics West - Biomedical Optics.

[9]  Bernhard Lendl,et al.  Tunable mid-infrared lasers in physical chemosensors towards the detection of physiologically relevant parameters in biofluids , 2012 .

[10]  N. Gretz,et al.  A quantitative look inside the body: minimally invasive infrared analysis in vivo. , 2014, Analytical chemistry.

[11]  Yargo Bonetti,et al.  External cavity quantum cascade laser tunable from 7.6 to 11.4 μm , 2009 .

[12]  Paul Bassan,et al.  Large scale infrared imaging of tissue micro arrays (TMAs) using a tunable Quantum Cascade Laser (QCL) based microscope. , 2014, The Analyst.

[13]  Bernhard Lendl,et al.  Direct determination of glucose, lactate and triglycerides in blood serum by a tunable quantum cascade laser-based mid-IR sensor , 2013 .

[14]  Rohit Bhargava,et al.  Fast Infrared Chemical Imaging with a Quantum Cascade Laser , 2014, Analytical chemistry.

[15]  A. Höskuldsson,et al.  Simultaneous determination of glucose, triglycerides, urea, cholesterol, albumin and total protein in human plasma by Fourier transform infrared spectroscopy: direct clinical biochemistry without reagents. , 2014, Clinical biochemistry.

[16]  Andreas Becker,et al.  Time-Resolved FT-IR Absorption Spectroscopy Using a Step-Scan Interferometer , 1991 .

[17]  Gerd Köhler,et al.  Bedside monitoring of subcutaneous interstitial glucose in healthy individuals using microdialysis and infrared spectrometry. , 2007, Journal of biomedical optics.

[18]  Jérôme Faist,et al.  External cavity quantum cascade laser , 2010 .

[19]  N. Newbury,et al.  Frequency characterization of a swept- and fixed-wavelength external-cavity quantum cascade laser by use of a frequency comb. , 2012, Optics express.

[20]  H. Michael Heise,et al.  Microdialysis based monitoring of subcutaneous interstitial and venous blood glucose in Type 1 diabetic subjects by mid-infrared spectrometry for intensive insulin therapy , 2008, SPIE BiOS.

[21]  Bernhard Lendl,et al.  Measures for optimizing pulsed EC-QC laser spectroscopy of liquids and application to multi-analyte blood analysis , 2013, Photonics West - Optoelectronic Materials and Devices.