Influence of spectral bandwidth limitations of tuneable external-cavity based quantum cascade laser systems for clinical biofluid analysis

In many publications, infrared spectroscopy excelled in multi-analyte assays of biofluids. Based on such technology, laboratory and point-of-care applications can be envisaged and most needed devices are for blood glucose measurements. Implementing strict glycemic control can reduce the risk of serious complications in both diabetic and critically ill patients. For this purpose, many different blood glucose monitoring techniques and insulin infusion strategies have been tested towards the realization of an artificial pancreas under closed loop control. However, for patient portable instrumentation current FTIR-spectrometers are still too bulky, which need replacement by devices that allow further miniaturization. Recently developed external cavity quantum cascade lasers (EC-QCL) are tuneable over about 200 cm-1, which however is still narrow, compared to the range accessible with FTIR-devices. In this work, we applied bandwidth constraints to previous FTIR-studies on blood plasma and dialysates of biofluids. For the clinically most important blood glucose no impairment was found using one laser only, provided that specific interferents were missing. Other analytes of interest, such as lactate and urea, indicated the need of broader tuneability over about 500 cm-1 with a second or third laser for a simultaneous glucose assay.

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

[2]  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.

[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]  John E. Bertie,et al.  Infrared Intensities of Liquids XX: The Intensity of the OH Stretching Band of Liquid Water Revisited, and the Best Current Values of the Optical Constants of H2O(l) at 25°C between 15,000 and 1 cm−1 , 1996 .

[5]  H. Michael Heise,et al.  Towards reagent-free blood glucose monitoring using micro-dialysis and infrared transmission spectrometry , 2006 .

[6]  H. M. Heise,et al.  Calibration modeling by partial least-squares and principal component regression and its optimization using an improved leverage correction for prediction testing , 1990 .

[7]  F. Capasso,et al.  Quantum cascade lasers in chemical physics , 2010 .

[8]  Federico Capasso,et al.  High-performance midinfrared quantum cascade lasers , 2010 .

[9]  H. Gremlich,et al.  Infrared and Raman Spectroscopy of Biological Materials , 2000 .

[10]  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.

[11]  H. Michael Heise,et al.  Bedside monitoring of subcutaneous interstitial glucose in type 1 diabetic subjects using microdialysis and infrared spectrometry with optimal correlation to blood glucose concentrations , 2007, SPIE BiOS.

[12]  T. Heise,et al.  Automated Near-Continuous Glucose Monitoring Measured in Plasma Using Mid-Infrared Spectroscopy , 2011, Journal of diabetes science and technology.

[13]  Grant Bochicchio,et al.  Glucose Measurement of Intensive Care Unit Patient Plasma Samples Using a Fixed-Wavelength Mid-Infrared Spectroscopy System , 2012, Journal of diabetes science and technology.

[14]  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 .

[15]  S. Leonhardt,et al.  Transmission infrared spectroscopy of whole blood – complications for quantitative analysis from leucocyte adhesion during continuous monitoring , 2010, Journal of biophotonics.

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

[17]  Claire F. Gmachl,et al.  In vitro measurements of physiological glucose concentrations in biological fluids using mid-infrared light , 2013, Biomedical optics express.

[18]  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.

[19]  Infrared spectroscopy in hemodialysis: reagent-free monitoring of patient detoxification by infrared spectroscopy , 2012, Analytical and Bioanalytical Chemistry.

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

[21]  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.

[22]  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.

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

[24]  Dachao Li,et al.  In vitro glucose measurement using tunable mid-infrared laser spectroscopy combined with fiber-optic sensor. , 2013, Biomedical optics express.

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

[26]  H. Michael Heise.  Biomedical Vibrational Spectroscopy – Technical Advances , 2007 .

[27]  Uwe Damm,et al.  Infrared Transmission Spectrometry for the Determination of Urea in Microliter Sample Volumes of Blood Plasma Dialysates , 2006, Applied spectroscopy.

[28]  H. Heise,et al.  Ex-vivo determination of blood glucose by microdialysis in combination with infrared attenuated total reflection spectroscopy , 1997 .