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Daneshgar S.,University College Cork | Daneshgar S.,Tyndall National Institute | De Feo O.,Solianis Monitoring AG | Kennedy M.P.,University College Cork | Kennedy M.P.,Tyndall National Institute
IEEE Transactions on Circuits and Systems I: Regular Papers | Year: 2010

The use of resonant injection-locked frequency dividers in frequency synthesizers has increased in recent years due to their lower power consumption compared to conventional digital prescalers. Numerous circuit ideas have been proposed, but there are few and sometimes contradictory estimates of the locking ranges (LRs) in these dividers. Despite several attempts, there is still no accurate analytical method to predict the LR. In this paper, we present a nonlinear approach based on the application of bifurcation theory to predict where the LR is wider rather than to say precisely how wide it is. The results presented have been derived by numerical bifurcation analysis using AUTO and have been verified by circuit simulations and experiments. In Part II, we will show how the insights developed in this paper lead to a rigorous design methodology. © 2010 IEEE.

Agency: Cordis | Branch: FP7 | Program: BSG-SME | Phase: SME-1 | Award Amount: 713.80K | Year: 2008

Blood glucose monitoring is important in the care of diabetes mellitus and is presently accomplished via a finger-stick in which a lancet is used to prick the finger and withdraw a small amount of blood for testing. The problem with the existing finger-stick-devices is that blood sampling is painful, it increases the risk for infections and the test is discontinuous. A method for measuring the status of a diabetes patient continuously is preferred, especially at night when the risk of undetected hypoglycaemia is present. Systems for continuous (non-invasive) blood glucose monitoring show promising results for measuring high blood glucose values (hyperglycaemia). However, these systems are not reliable when it comes to measuring low blood glucose values (hypoglycaemia). This is due to the fact that a small variation in the blood glucose concentration in the hypo-region has a great impact on the status of the patient. In this project volatile components emanated from the skin are used to determine the state of diabetes patient; one of these components is acetone. An apparatus to clinically test the relation between the amount of acetone and the state of hypoglycaemia (and the concentration of blood glucose) has to be developed. Clinical tests (clamp tests) will be performed in an (academic)hospital. Furthermore, research has to be performed into the combination of several techniques (e.g. impedance spectroscopy) with skin gas measurements to obtain an overall picture of the status of a diabetes patient. Measurements of acetone permeation through the skin and the use of membranes to protect the sensor and/or to enhance the signal are needed. Sensors need to be developed to miniaturise the system. The ultimate goal is to develop a sensing system capable of measuring the condition of a diabetes patient satisfactory and in addition is able to steer the function of, among others an insulin pump.

Huclova S.,ETH Zurich | Baumann D.,ETH Zurich | Talary M.S.,Solianis Monitoring AG | Frohlich J.,ETH Zurich
Physics in Medicine and Biology | Year: 2011

The sensitivity and specificity of dielectric spectroscopy for the detection of dielectric changes inside a multi-layered structure is investigated. We focus on providing a base for sensing physiological changes in the human skin, i.e. in the epidermal and dermal layers. The correlation between changes of the human skin's effective permittivity and changes of dielectric parameters and layer thickness of the epidermal and dermal layers is assessed using numerical simulations. Numerical models include fringing-field probes placed directly on a multi-layer model of the skin. The resulting dielectric spectra in the range from 100 kHz up to 100 MHz for different layer parameters and sensor geometries are used for a sensitivity and specificity analysis of this multi-layer system. First, employing a coaxial probe, a sensitivity analysis is performed for specific variations of the parameters of the epidermal and dermal layers. Second, the specificity of this system is analysed based on the roots and corresponding sign changes of the computed dielectric spectra and their first and second derivatives. The transferability of the derived results is shown by a comparison of the dielectric spectra of a coplanar probe and a scaled coaxial probe. Additionally, a comparison of the sensitivity of a coaxial probe and an interdigitated probe as a function of electrode distance is performed. It is found that the sensitivity for detecting changes of dielectric properties in the epidermal and dermal layers strongly depends on frequency. Based on an analysis of the dielectric spectra, changes in the effective dielectric parameters can theoretically be uniquely assigned to specific changes in permittivity and conductivity. However, in practice, measurement uncertainties may degrade the performance of the system. © 2011 Institute of Physics and Engineering in Medicine.

Caduff A.,Solianis Monitoring AG | Mueller M.,Solianis Monitoring AG | Megej A.,Solianis Monitoring AG | Dewarrat F.,Solianis Monitoring AG | And 7 more authors.
Biosensors and Bioelectronics | Year: 2011

The Multisensor Glucose Monitoring System (MGMS) features non invasive sensors for dielectric characterisation of the skin and underlying tissue in a wide frequency range (1 kHz-100. MHz, 1 and 2. GHz) as well as optical characterisation. In this paper we describe the results of using an MGMS in a miniaturised housing with fully integrated sensors and battery.Six patients with Type I Diabetes Mellitus (age 44±16y; BMI 24.1±1.3kg/m2, duration of diabetes 27±12y; HbA1c 7.3±1.0%) wore a single Multisensor at the upper arm position and performed a total of 45 in-clinic study days with 7 study days per patient on average (min. 5 and max. 10). Glucose changes were induced either orally or by i.v. glucose administration and the blood glucose was measured routinely. Several prospective data evaluation routines were applied to evaluate the data. The results are shown using one of the restrictive data evaluation routines, where measurements from the first 22 study days were used to train a linear regression model. The global model was then prospectively applied to the data of the remaining 23 study days to allow for an external validation of glucose prediction. The model application yielded a Mean Absolute Relative Difference of 40.8%, a Mean Absolute Difference of 51.9mgdL-1, and a correlation of 0.84 on average per study day. The Clarke error grid analyses showed 89.0% in A+B, 4.5% in C, 4.6% in D and 1.9% in the E region.Prospective application of a global, purely statistical model, demonstrates that glucose variations can be tracked non invasively by the MGMS in most cases under these conditions. © 2011 Elsevier B.V.

Skipetrov S.E.,CNRS Physics and Models in Condensed Media Laboratory | Peuser J.,University of Fribourg | Cerbino R.,University of Fribourg | Cerbino R.,University of Milan | And 3 more authors.
Optics Express | Year: 2010

We study the noise of the intensity variance and of the intensity correlation and structure functions measured in light scattering from a random medium in the case when these quantities are obtained by averaging over a finite number N of pixels of a digital camera. We show that the noise scales as 1/N in all cases and that it is sensitive to correlations of signals corresponding to adjacent pixels as well as to the effective time averaging (due to the finite integration time) and spatial averaging (due to the finite pixel size). Our results provide a guide to estimation of noise levels in such applications as multi-speckle dynamic light scattering, time-resolved correlation spectroscopy, speckle visibility spectroscopy, laser speckle imaging etc. © 2010 Optical Society of America.

Zanon M.,University of Padua | Riz M.,University of Padua | Sparacino G.,University of Padua | Facchinetti A.,University of Padua | And 3 more authors.
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2011

New scenarios in diabetes treatment have been opened in the last ten years by continuous glucose monitoring (CGM) sensors. In particular, Non-Invasive CGM sensors are particularly appealing, even though they are still at an early stage of development. Solianis Monitoring AG (Zrich, Switzerland) has proposed an approach based on a multisensor concept, embedding primarily dielectric spectroscopy and optical sensors. This concept requires a mathematical model able to reconstruct the glucose concentration from the 150 channels measured with the device. Assuming a multivariate linear regression model (valid and usable for different individuals), the aim of this paper is the assessment of some techniques usable for determining such a model, namely Ordinary Least Squares (OLS), Partial Least Squares (PLS) and Least Absolute Shrinkage and Selection Operator (LASSO). Once the model is identified on a training set, the accuracy of prospective glucose profiles estimated from unseen multisensor data is assessed. Preliminary results obtained from 18 in-clinic study days show that sufficiently accurate reconstruction of glucose levels can be achieved if suitable model identification techniques, such as LASSO, are considered. © 2011 IEEE.

Caduff A.,Solianis Monitoring AG | Talary M.S.,Solianis Monitoring AG | Zakharov P.,Solianis Monitoring AG
Diabetes Technology and Therapeutics | Year: 2010

It is widely accepted that noninvasive glucose monitoring (NIGM) has the potential to revolutionize diabetes therapy. However, current approaches to NIGM studied to date have not yet demonstrated a level of acceptable functionality to allow real-time use, beyond restricted fields of application. A number of reviews have been devoted to the subject of NIGM with different focuses related to challenges and a description of the respective underlying problems. This review is aimed at addressing a fundamental topic in the application of NIGM that seems to have received less attention, by describing the perturbations that result in a reduced functionality of NIGM in daily use. Here we provide a short general introduction to glucose monitoring and a basic illustration of the electromagnetic spectrum with a description of the respective physical mechanisms underlying the measurement techniques. This allows for a better understanding of how these perturbing factors affect the measured properties. Cutaneous blood perfusion is one of the major perturbing factors to NIGM, along with variations in temperature, migration of water, and the effect of attachment of the sensor to the skin. An understanding of the mechanisms underlying perfusion variation over time and within the measured human skin tissue matrix is required to enable a discrimination between glucose-induced effects within the tissue and various biophysical impacts to be made. It is suggested that a plurality of probing frequencies is required to discriminate glucose-related changes from the perturbations. A system designed to perform the measurements in different regions of the electromagnetic spectrum with dedicated sensors (multisensor approach) has the potential to more efficiently and reliably discriminate glucose-related information from perturbations. This can be achieved by combining signals related to measurements with different physical underlying mechanisms of the interaction between the probing field propagation and the tissue to help account for the different sources of perturbations. Copyright 2010, Mary Ann Liebert, Inc.

Zakharov P.,Solianis Monitoring AG | Talary M.S.,Solianis Monitoring AG | Kolm I.,University of Zürich | Caduff A.,Solianis Monitoring AG
Physiological Measurement | Year: 2010

Changes in morphology of the skin are an important factor that can affect non-invasive measurements performed through this organ, in particular for glucose monitoring in e.g. patients with diabetes mellitus. A characterization technique for non-contact in vivo profiling of the superficial skin layers can be beneficial for evaluation of the performance of such measurement systems. We applied a full-field optical coherence tomography (OCT) system followed by the fully automatic processing for this task. With the developed procedure, non-invasive quantification of the skin morphology can be performed within a few minutes. The dorsal skin of the upper arm of 22 patients with Type 1 Diabetes Mellitus was investigated with an OCT system and with a commercially available dermatological laser scanning confocal microscope (CM) as a reference method. The estimates of epidermal thickness from OCT were compared with the results of expert-assisted analysis of confocal images. The highest correlation with the CM measurements has been obtained for the distance from the entrance peak to the first minimum of the OCT reflection profile (). In this specific patient group, we have observed a statistically significant correlation of the subjects' body mass index with the distance from the entrance peak to the dermal reflection peak in the OCT profile (p = 0.010). Furthermore, the same OCT parameter is negatively correlated with age with marginal statistical significance (p = 0.062). At the same time, no relation of diabetes-related parameters (duration of disease and concentration of glycated haemoglobin) to the skin morphology observed with the OCT and CM was found. © 2010 Institute of Physics and Engineering in Medicine.

Zakharov P.,Solianis Monitoring AG | Dewarrat F.,Solianis Monitoring AG | Caduff A.,Solianis Monitoring AG | Talary M.S.,Solianis Monitoring AG
Physiological Measurement | Year: 2011

A wearable system incorporating sensors for dielectric and optical spectroscopy was used to study skin properties and their dependence on the cutaneous blood content (CBC). Simultaneous measurements with both modalities were carried out on the upper arm during blood perfusion-provoking exercises performed by four subjects in four separate sets of experiments. By relating changes in the attenuation of green (central wavelength λc = 568 nm) and infrared (λc = 798 nm) light, the ratio of mean pathlengths travelled by photons in the skin blood plexus was obtained. The pathlength for infrared light is found to be 3.85 times larger than for green. Combining signals of two wavelengths and accounting for pathlength difference, we quantitatively characterize the CBC as a cumulative optical thickness of red blood cells in the skin plexus. The dielectric spectra of skin in the MHz range were fitted with the Cole-Cole model and the changes of parameters were quantitatively related to the optically derived changes in CBC using a linear regression analysis. The positive correlation with CBC is obtained for the dispersion exponent (R2 = 0.68), and the negative-for the dispersion time (R2 = 0.40). Thus dielectric dispersion of the skin gets broader and shifts towards lower frequencies with an increase of CBC. © 2011 Institute of Physics and Engineering in Medicine Printed in the UK.

Daneshgar S.,Tyndall National Institute | De Feo O.,Solianis Monitoring AG | Kennedy M.P.,Tyndall National Institute
IEEE Transactions on Circuits and Systems I: Regular Papers | Year: 2011

An intuitive approach to analyze the behavior of an LC Injection-Locked Frequency Divider was presented in Part I of this work; that paper provided insight into the locking behavior in the valid design area of the circuit. In this paper, we present a rigorous design methodology which provides a closed form equation showing where the locking range is wider. Theoretical predictions of the locked regions are verified by simulations of the circuit in Spectre RF using 0.35-μm CMOS technology models. © 2010 IEEE.

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