Predicting the early risk of chronic kidney disease in patients with diabetes using real-world data.

Diagnostic procedures, therapeutic recommendations, and medical risk stratifications are based on dedicated, strictly controlled clinical trials. However, a plethora of real-world medical data exists, whereupon the increase in data volume comes at the expense of completeness, uniformity, and control. Here, a case-by-case comparison shows that the predictive power of our real world data-based model for diabetes-related chronic kidney disease outperforms published algorithms, which were derived from clinical study data.

Biomedical applications of mid-infrared quantum cascade lasers - a review.

Mid-infrared spectroscopy has been applied to research in biology and medicine for more than 20 years and conceivable applications have been identified. More recently, these applications have been shown to benefit from the use of quantum cascade lasers due to their specific properties, namely high spectral power density, small beam parameter product, narrow emission spectrum and, if needed, tuning capabilities. This review provides an overview of the achievements and illustrates some applications which benefit from the key characteristics of quantum cascade laser-based mid-infrared spectroscopy using examples such as breath analysis, the investigation of serum, non-invasive glucose monitoring in bulk tissue and the combination of spectroscopy and microscopy of tissue thin sections for rapid histopathology.

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

Continuous glucose monitoring enables an improved disease management for people with diabetes. However, state-of-the-art, enzyme-based, minimally invasive sensors lose their sensitivity over time and have to be replaced periodically. Here, we present the in vitro investigation of a quantum cascade laser-based measurement scheme that conceptually should be applicable over elongated periods of time due to its reagent-free nature and may therefore be considered as an approach towards long-term implantation.

On the role of interference in laser-based mid-infrared widefield microspectroscopy.

A laser's high degree of coherence leads to interferences, which-in the absence of precautions-can cause severe image distortions such as fringes and speckles and which thereby strongly hamper a meaningful interpretation of hyperspectral images in laser-based widefield microspectroscopy. While images and spectra of homogenous samples may already suffer from interferences, any structured object such as a tissue thin section will add to these distortions due to wavelength- and, in particular, sample-dependent phase shifts (structure sizes, absorption coefficients, refractive indices). This effect is devastating for the universal applicability of laser-based microspectroscopy especially in the mid-infrared (MIR), where cell sizes are of the same dimension as the wavelength of the illumination source.

Optical properties of porcine dermis in the mid-infrared absorption band of glucose.

The optical properties of skin in the mid-infrared range are not known, despite their importance for e.g. non-invasive glucose monitoring.

Translating vibrational spectroscopy into clinical applications - vision or reality?

The Faraday Discussion meeting "Advanced Vibrational Spectroscopy for Biomedical Applications" provided an excellent opportunity to share and discuss recent research and applications on a highly interdisciplinary level. Spectral pathology, single cell analysis, data handling, clinical spectroscopy, and the spectral analysis of biofluids were among the topics covered during the meeting. The focus on discussion rather than "merely" presentation was highly appreciated and fruitful discussions evolved around the interpretation of the amide-bands, optical resolution, the role of diffraction and data analysis procedure, to name a few.

Real-time mid-infrared imaging of living microorganisms.

The speed and efficiency of quantum cascade laser-based mid-infrared microspectroscopy are demonstrated using two different model organisms as examples. For the slowly moving Amoeba proteus, a quantum cascade laser is tuned over the wavelength range of 7.6 µm to 8.

Surface-enhanced mid-infrared spectroscopy using a quantum cascade laser.

We report on the successful measurement of surface-enhanced infrared vibrational spectra from a few nanometer thick organic semiconductor layers on samples with resonant plasmonic nanoantennas arranged in arrays. For the first time, a setup with a tunable quantum cascade laser as the light source in mid-infrared range is used. The combination of the quantum cascade laser with a microbolometer array for infrared light allows to map an area 2.

A fast recoiling silk-like elastomer facilitates nanosecond nematocyst discharge.

Background: The discharge of the Cnidarian stinging organelle, the nematocyst, is one of the fastest processes in biology and involves volume changes of the highly pressurised (150 bar) capsule of up to 50%. Hitherto, the molecular basis for the unusual biomechanical properties of nematocysts has been elusive, as their structure was mainly defined as a stress-resistant collagenous matrix.

Results: Here, we characterise Cnidoin, a novel elastic protein identified as a structural component of Hydra nematocysts.

A quantitative look inside the body: minimally invasive infrared analysis in vivo.

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.

Quantum cascade laser-based hyperspectral imaging of biological tissue.

The spectroscopy of analyte-specific molecular vibrations in tissue thin sections has opened up a path toward histopathology without the need for tissue staining. However, biomedical vibrational imaging has not yet advanced from academic research to routine histopathology due to long acquisition times for the microscopic hyperspectral images and/or cost and availability of the necessary equipment. Here we show that the combination of a fast-tuning quantum cascade laser with a microbolometer array detector allows for a rapid image acquisition and bares the potential for substantial cost reduction.

Evaporation from open microchannel grooves.

The evaporation of water from open u-shaped microchannel grooves was investigated with particular emphasis on the roles of channel width and air flow conditions. Given the small dimensions of the microchannels, all measurements were conducted in a range where convection and diffusion are of equal importance and known correlations for the calculation of mass transfer coefficients cannot be applied. The evaporation rates were measured using a new optical method and a gravimetric method.

Fluorescence properties of carba nicotinamide adenine dinucleotide for glucose sensing.

Carba nicotinamide adenine dinucleotide (cNAD) may serve as a stable cofactor for the enzyme-based detection of glucose. Many characteristics of cNAD and its reduced form cNADH resemble those of NAD and NADH, respectively. The fluorescence lifetimes of cNADH are determined to be 0.

Effective fragment potential study of the influence of hydration on the vibrational spectrum of glucose.

The standard agent glucose has been the subject of numerous experimental and theoretical studies, especially in the aqueous environments which are present in most biochemical processes. The impact of the solvation process on the vibrational spectra of glucose in the mid-infrared region is investigated in this work. The computational study focused both on the variation of the number of surrounding water molecules from 0 to 229 and on the number of single spectra included in the iterative averaging process.

Continuous glucose monitoring by means of mid-infrared transmission laser spectroscopy in vitro.

The continuous surveillance of glucose concentration reduces short-term risks and long-term complications for people with diabetes mellitus, a disorder of glucose metabolism. As a first step towards the continuous monitoring of glucose, reagent-free transmission spectroscopy in the mid-infrared region has been carried out in vitro using a quantum cascade laser and an optical silver halide fiber. A 30 μm gap in the fiber allowed for transmission spectroscopy of aqueous glucose solutions at a wavelength of 9.

A comparison of random forest and its Gini importance with standard chemometric methods for the feature selection and classification of spectral data.

Background: Regularized regression methods such as principal component or partial least squares regression perform well in learning tasks on high dimensional spectral data, but cannot explicitly eliminate irrelevant features. The random forest classifier with its associated Gini feature importance, on the other hand, allows for an explicit feature elimination, but may not be optimally adapted to spectral data due to the topology of its constituent classification trees which are based on orthogonal splits in feature space.

Results: We propose to combine the best of both approaches, and evaluated the joint use of a feature selection based on a recursive feature elimination using the Gini importance of random forests' together with regularized classification methods on spectral data sets from medical diagnostics, chemotaxonomy, biomedical analytics, food science, and synthetically modified spectral data.

Multivariate feature selection and hierarchical classification for infrared spectroscopy: serum-based detection of bovine spongiform encephalopathy.

A hierarchical scheme has been developed for detection of bovine spongiform encephalopathy (BSE) in serum on the basis of its infrared spectral signature. In the first stage, binary subsets between samples originating from diseased and non-diseased cattle are defined along known covariates within the data set. Random forests are then used to select spectral channels on each subset, on the basis of a multivariate measure of variable importance, the Gini importance.

Quantitative analysis of serum and serum ultrafiltrate by means of Raman spectroscopy.

The fast and reliable determination of concentrations of blood, plasma or serum constituents is a major requirement in clinical chemistry. We explored Raman spectroscopy as a reagent-free tool for predicting the concentrations of different parameters in serum and serum ultrafiltrate. In an investigation using samples from 247 blood donors (which we believe to be the largest study on Raman spectroscopy of serum so far) the concentrations of glucose, triglycerides, urea, total protein, cholesterol, high density lipoprotein, low density lipoprotein and uric acid were determined with an accuracy within the clinically interesting range.

Antemortem identification of bovine spongiform encephalopathy from serum using infrared spectroscopy.

Since 1986, more than 180 000 clinical cases of bovine spongiform encephalopathy (BSE) have been observed in the U.K. alone.