H. Michael Heise

Spectral Variable Selection for Partial Least Squares Calibration Applied to Authentication and Quantification of Extra Virgin Olive Oils Using Fourier Transform Raman Spectroscopy

The limits of quantitative multivariate assays for the analysis of extra virgin olive oil samples from various Greek sites adulterated by sunflower oil have been evaluated based on their Fourier transform (FT) Raman spectra. Different strategies for wavelength selection were tested for calculating optimal partial least squares (PLS) models. Compared to the full spectrum methods previously applied, the optimum standard error of prediction (SEP) for the sunflower oil concentrations in spiked olive oil samples could be significantly reduced. One efficient approach (PMMS, pair-wise minima and maxima selection) used a special variable selection strategy based on a pair-wise consideration of significant respective minima and maxima of PLS regression vectors, calculated for broad spectral intervals and a low number of PLS factors. PMMS provided robust calibration models with a small number of variables. On the other hand, the Tabu search strategy recently published (search process guided by restrictions leading to Tabu list) achieved lower SEP values but at the cost of extensive computing time when searching for a global minimum and less robust calibration models. Robustness was tested by using packages of ten and twenty randomly selected samples within cross-validation for calculating independent prediction values. The best SEP values for a one years harvest with a total number of 66 Cretian samples were obtained by such spectral variable optimized PLS calibration models using leave-20-out cross-validation (values between 0.5 and 0.7% by weight). For the more complex population of olive oil samples from all over Greece (total number of 92 samples), results were between 0.7 and 0.9% by weight with a cross-validation sample package size of 20. Notably, the calibration method with Tabu variable selection has been shown to be a valid chemometric approach by which a single model can be applied with a low SEP of 1.4% for olive oil samples across three different harvest years.

Glucose Quantification in Dried-down Nanoliter Samples Using Mid-Infrared Attenuated Total Reflection Spectroscopy

The aim of this study was to determine the feasibility of minimally invasive glucose concentration measurement of a body fluid within the physiologically important range below 100 nL with a number of samples such as interstitial fluid, plasma, or whole blood using mid-infrared spectroscopy, but starting with preliminary measurements on samples of simple aqueous glucose solutions. The Fourier transform infrared spectrometer was equipped with a Golden Gate® single reflection diamond attenuated total reflection (ATR) accessory and a room-temperature pyroelectric detector. As the necessary detection limits can be achieved only for dried samples within the spectrometric conditions realized by a commercial instrument, the work focused on the optimization of such ATR measurements. We achieved quantification of samples with volumes as low as 7 nL between 10 and 600 mg/dL. The standard error of prediction (SEP) for the concentration range 10–100 mg/dL is 3.2 mg/dL with full interval data between 1180 and 940 cm−1. The performance of the prediction is given by a coefficient of variation of prediction (CVpred) of 6.2%. When all samples within the whole concentration range are included, the SEP increases to 20.2 mg/dL, and hence the CVpred to 10.6% due to a nonlinear signal dependence on glucose concentration. A detection limit for glucose of 0.7 ng with a signal-to-noise ratio of 10 was obtained.

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

Background: Glycemic control can reduce the mortality and morbidity of intensive care patients. The CLINICIP (closed-loop insulin infusion for critically ill patients) project aimed to develop a closed-loop control system for this patient group. Following a stepwise approach, we combined three independently tested subparts to form a semiautomatic closed-loop system and evaluated it with respect to safety and performance aspects by testing it in subjects with type 1 diabetes mellitus (T1DM) in a first feasibility trial. Methods: Vascular microdialysis, a multianalyte infrared spectroscopic glucose sensor, and a standard insulin infusion pump controlled by an adaptive model predictive control (MPC) algorithm were combined to form a closed-loop device, which was evaluated in four T1DM subjects during 30-hour feasibility studies. The aim was to maintain blood glucose concentration in the target range between 80 and 110 mg/dl. Results: Mean plasma glucose concentration was 110.5 ± 29.7 mg/dl. The MPC managed to establish normoglycemia within 105 ± 78 minutes after trial start and managed to maintain glucose concentration within the target range for 47% of the time. The hyperglycemic index averaged to 11.9 ± 5.3 mg/dl. Conclusion: Data of the feasibility trial illustrate the device being effective in controlling glycemia in T1DM subjects. However, the monitoring part of the loop must be improved with respect to accuracy and precision before testing the system in the target population.

Infrared Transmission Spectrometry for the Determination of Urea in Microliter Sample Volumes of Blood Plasma Dialysates

Application of mid-infrared spectroscopy for the determination of urea in blood plasma dialysates of microliter sample volumes using a transmission microcell was investigated. Infrared spectra of the dialysates of plasma samples collected from 75 different patients using CMA 60 microdialysis catheters were evaluated with multivariate partial least squares regression. Using the absorbance spectral data from 1520–1420 cm−1 and 1220–1120 cm−1, a minimum standard error of prediction (SEP) of 0.88 mg/dL (0.14 mM) was achieved with spectral variable selection. Our findings suggest the feasibility of developing a mid-infrared sensor in combination with micro-fluidics for on-line monitoring of urea in patients undergoing dialysis treatment.

Transmission infrared spectroscopy of whole blood – complications for quantitative analysis from leucocyte adhesion during continuous monitoring

Infrared spectroscopy has been applied to analyse glucose and cellular components in whole blood with the aim of developing an online clinical diagnostic and monitoring modality. Leucocyte adsorption onto the CaF(2) windows was observed over a period of several hours under continuous blood flow using a transmission cell of 30 mum path length. This build-up of cellular material on the windows is responsible for diminishing the sample path length under the flow conditions chosen. The adsorption dynamics have been characterised and their impact on glucose monitoring is reported. For short-term monitoring (<2 hours) a standard error of prediction of 11 mg/dL with human citrated blood samples from three different subjects was achieved. Furthermore, the leucocyte build-up was also reported for porcine EDTA blood monitoring. Consequences and testing opportunities with regard to the first stages in the immune cell reaction to the exposure of body-foreign materials to anticoagulated whole blood are discussed.

Microdialysis based monitoring of subcutaneous interstitial and venous blood glucose in Type 1 diabetic subjects by mid-infrared spectrometry for intensive insulin therapy

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. In contrast to competing subcutaneously implanted electrochemical biosensors, microdialysis based systems for sampling body fluids from either the interstitial adipose tissue compartment or from venous blood have been developed, which allow an ex-vivo glucose monitoring by mid-infrared spectrometry. For the first option, a commercially available, subcutaneously inserted CMA 60 microdialysis catheter has been used routinely. The vascular body interface includes a double-lumen venous catheter in combination with whole blood dilution using a heparin solution. The diluted whole blood is transported to a flow-through dialysis cell, where the harvesting of analytes across the microdialysis membrane takes place at high recovery rates. The dialysate is continuously transported to the IR-sensor. Ex-vivo measurements were conducted on type-1 diabetic subjects lasting up to 28 hours. Experiments have shown excellent agreement between the sensor readout and the reference blood glucose concentration values. The simultaneous assessment of dialysis recovery rates renders a reliable quantification of whole blood concentrations of glucose and metabolites (urea, lactate etc) after taking blood dilution into account. Our results from transmission spectrometry indicate, that the developed bed-side device enables reliable long-term glucose monitoring with reagent- and calibration-free operation.

Eunice C.Y. Li-Chan, Peter R. Griffiths, and John M. Chalmers (Eds.): Applications of vibrational spectroscopy in food science

Book’s topic Food science and technology is a rather broad field with many facets of analytical chemistry. Vibrational spectroscopy—as mid and near-infrared or Raman spectroscopy—can be regarded as “green methods”, because they are reagent-free and non-destructive. Such reliable and powerful analytical methods are also required for process analysis and quality control in many fields of application of foods and beverages. This two-volume book provides comprehensive coverage of instrumentation, chemometrics, and method applications in food science. Studies on special foodstuffs illustrate the wide applicability of vibrational spectroscopy as a versatile means of analysis in food science.

Noninvasive Monitoring of Blood Glucose Using Color-Coded Photoplethysmographic Images of the Illuminated Fingertip Within the Visible and Near-Infrared Range: Opportunities and Questions

Noninvasive blood glucose assays have been promised for many years and various molecular spectroscopy-based methods of skin are candidates for achieving this goal. Due to the small spectral signatures of the glucose used for direct physical detection, moreover hidden among a largely variable background, broad spectral intervals are usually required to provide the mandatory analytical selectivity, but no such device has so far reached the accuracy that is required for self-monitoring of blood glucose (SMBG). A recently presented device as described in this journal, based on photoplethysmographic fingertip images for measuring glucose in a nonspecific indirect manner, is especially evaluated for providing reliable blood glucose concentration predictions.

Combination of micro-dialysis and infrared spectroscopy: a multianalyte assay for accurate biofluid analysis and patient monitoring

Micro-dialysis can be used for continuously harvesting body fluids, while a multi-component analysis of the dialysates by infrared spectrometry offers splendid opportunities for monitoring substrates and metabolites such as glucose, lactate and others small enough to penetrate the semi-permeable dialysis membranes. However, a drawback of this process are variable recovery rates, which can be observed especially for subcutaneously implanted catheters in human subjects. Isotonic perfusates were investigated with acetate and mannitol as recovery markers for the dialysis of human serum at 37°C to mimic in vivo patient monitoring. The latter non-ionic substance has been suggested for application when other ionic substances such as bicarbonate or pH are also to be determined. Simultaneously for acetate and mannitol, the depletion of the marker substances from the perfusates using different micro-dialysis devices was investigated under various flow-rates. Relationships between relative dialysate marker concentrations and glucose recovery rates were determined based on multivariate calibrations. For quantification, classical least squares with reference spectra for modelling the serum dialysates was used, rendering a basis for reliable blood glucose and lactate measurements.

Surface Ultra-Structure and Size of Human Corneocytes from Upper Stratum Corneum Layers of Normal and Diabetic Subjects with Discussion of Cohesion Aspects

Background: During the final stage of differentiation of cornified squamous epithelia like the human skin epidermis, anucleated corneocytes are formed. Formation of the horny layer and its ongoing desquamation are fundamental processes leading to the formation of an efficient epidermal barrier. Materials and methods: For a better understanding of the desquamation process, the role of corneocyte surface ultra-structure has been investigated using a special preparation technique for scanning electron microscopy (SEM). Human morphologically different corneocytes from the stratum corneum of the fingertip, the thenar eminence (thick skin), and the wrist below the carpus (thin skin) of normal and diabetic subjects were obtained by adhesive tape stripping. Results: The inside surface structure of corneocytes from thick skin shows prominent nubs, which are broader and more extended than those of thin skin. Towards their outside, corneocytes were flat with cavities as indentations of the nubs from neighboured cells providing clues on the mechanical strength of the ‘intercellular stickiness’. As the size of thin skin corneocytes for diabetic subjects was also studied, it was found that their area was slightly nonlinearly dependent on age. Conclusion: Accordingly to a reduced proliferation and differentiation rate, as postulated for diabetic persons, differences in size were as expected but statistically not significant, compared with corneocytes under normal homeostasis conditions. For discussion is a model, for which the interwoven cellular connectivity provides additional mechanical strength for the stratum corneum in thick skin.