Photonic Biosensors: Detection, Analysis and Medical Diagnostics

The role of nanotechnologies in personalized medicine is rising remarkably in the last decade because of the ability of these new sensing systems to diagnose diseases from early stages and the availability of continuous screenings to characterize the efficiency of drugs and therapies for each single patient. Recent technological advancements are allowing the development of biosensors in low-cost and user-friendly platforms, thereby overcoming the last obstacle for these systems, represented by limiting costs and low yield, until now. In this context, photonic biosensors represent one of the main emerging sensing modalities because of their ability to combine high sensitivity and selectivity together with real-time operation, integrability, and compatibility with microfluidics and electric circuitry for the readout, which is fundamental for the realization of lab-on-chip systems. This book, “Photonic Biosensors: Detection, Analysis and Medical Diagnostics”, has been published thanks to the contributions of the authors and collects research articles, the content of which is expected to assume an important role in the outbreak of biosensors in the biomedical field, considering the variety of the topics that it covers, from the improvement of sensors’ performance to new, emerging applications and strategies for on-chip integrability, aiming at providing a general overview for readers on the current advancements in the biosensing field

A System of ODEs for Representing Trends of CGM Signals

Diabetes Mellitus is a metabolic disorder which may result in severe and potentially fatal complications if not well-treated and monitored. In this study, a quantitative analysis of the data collected using CGM (Continuous Glucose Monitoring) devices from eight subjects with type 2 diabetes in good metabolic control at the University Polyclinic Agostino Gemelli, Catholic University of the Sacred Heart, was carried out. In particular, a system of ordinary differential equations whose state variables are affected by a sequence of stochastic perturbations was proposed and used to extract more informative inferences from the patients' data. For this work, Matlab and R programs were used to find the most appropriate values of the parameters (according to the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC)) for each patient. Fitting was carried out by Particle Swarm Optimization to minimize the ordinary least squares error between the observed CGM data and the data from the ODE model. Goodness of fit tests were made in order to assess which probability distribution was best suitable for representing the waiting times computed from the model parameters. Finally, both parametric and non-parametric density estimation of the frequency histograms associated with the variability of the glucose elimination rate from blood were conducted and their representative parameters assessed from the data. The results show that the chosen models succeed in capturing most of the glucose fluctuations for almost every patient

Multimodel Approaches for Plasma Glucose Estimation in Continuous Glucose Monitoring. Development of New Calibration Algorithms

ABSTRACT Diabetes Mellitus (DM) embraces a group of metabolic diseases which main characteristic is the presence of high glucose levels in blood. It is one of the diseases with major social and health impact, both for its prevalence and also the consequences of the chronic complications that it implies. One of the research lines to improve the quality of life of people with diabetes is of technical focus. It involves several lines of research, including the development and improvement of devices to estimate "online" plasma glucose: continuous glucose monitoring systems (CGMS), both invasive and non-invasive. These devices estimate plasma glucose from sensor measurements from compartments alternative to blood. Current commercially available CGMS are minimally invasive and offer an estimation of plasma glucose from measurements in the interstitial fluid CGMS is a key component of the technical approach to build the artificial pancreas, aiming at closing the loop in combination with an insulin pump. Yet, the accuracy of current CGMS is still poor and it may partly depend on low performance of the implemented Calibration Algorithm (CA). In addition, the sensor-to-patient sensitivity is different between patients and also for the same patient in time. It is clear, then, that the development of new efficient calibration algorithms for CGMS is an interesting and challenging problem. The indirect measurement of plasma glucose through interstitial glucose is a main confounder of CGMS accuracy. Many components take part in the glucose transport dynamics. Indeed, physiology might suggest the existence of different local behaviors in the glucose transport process. For this reason, local modeling techniques may be the best option for the structure of the desired CA. Thus, similar input samples are represented by the same local model. The integration of all of them considering the input regions where they are valid is the final model of the whole data set. Clustering is tBarceló Rico, F. (2012). Multimodel Approaches for Plasma Glucose Estimation in Continuous Glucose Monitoring. Development of New Calibration Algorithms [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/17173Palanci

The Role of Fluorescence and Human Factors in Quantitative Transdermal Blood and Tissue Analysis Using NIR Raman Spectroscopy

This research is part of an ongoing project aimed at the application of combined near infrared (NIR) Raman and fluorescence spectroscopy to noninvasive in vivo blood analysis including but not limited to glucose monitoring. Coping with practicalities of human factors and exploring ways to obtain and use knowledge gained about autofluorescence to improve algorithms for blood and tissue analysis are the general goals of this research. Firstly, the study investigated the various sources of human factors pertinent to our concerns, such as fingerprints, turgor, skin hydration and pigmentation. We then introduced specialized in vivo apparatus including means for precise and reproducible placement of the tissues relative to the optical aperture, i.e., the position detector pressure monitor (PDPM). Based on solid instrumental performances, appropriate methodology is now provided for applying and maintaining pressure to keep surface tissues immobile during experiments while obtaining the desired blood content and flow. Secondly, in vivo human fingertip skin autofluorescence photobleaching under 200 mW 830 nm NIR irradiation is observed and it is characterized that: i) the majority of the photobleached fluorescence originates from static tissue not blood, ii) the bleaching (1/e point) occurs in 101-102 sec timescale, and also iii) a photobleached region remains bleached for at least 45 min but recovers completely within several hours. A corresponding extensive but not exhaustive in vitro systematic study narrowed down the major contributors of such fluorescence and bleaching to collagen, melanin, plasma and hemoglobin: two major static tissue constituents and two major blood proteins. Thirdly, we established that measuring the inelastic and elastic emissions simultaneously leads to a sensitive probe for volume changes of both red blood cells and plasma. An algorithm based on measurements obtained while performing research needed for this thesis, as well as some empirical calibration approaches, was presented. The calibrated algorithm showed real potential to track hematocrit variations in cardiac pulses, centrifugal loading, blood vessel blockage using tourniquet, and even during as subtle an occurrence as in a Valsalva maneuver. Finally, NIR fluorescence and photochemistry of pentosidine, a representative of the advanced glycation endproducts (AGEs) which accumulate with age and hyperglycemia, was studied. The results indicate that oxygen plays a pivotal role in its photobleaching process. We hypothesized and offered proofs showing that pentosidine is a 1O2 sensitizer that is also subject to attack by the 1O2 resulting in the photobleaching that is observed when probing tissue using NIR. The photobleaching reaction is kinetically first order in pentosidine and ground state oxygen, and in vivo effectively first order with NIR irradiation also

Micro/nanofluidic and lab-on-a-chip devices for biomedical applications

Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [1]. Because of their adaptability, feasibility, and cost-efficiency, these devices can revolutionize the future of preclinical technologies. Furthermore, they allow insights into the performance and toxic effects of responsive drug delivery nanocarriers to be obtained, which consequently allow the shortcomings of two/three-dimensional static cultures and animal testing to be overcome and help to reduce drug development costs and time [2–4]. With the constant advancements in biomedical technology, the development of enhanced microfluidic devices has accelerated, and numerous models have been reported. Given the multidisciplinary of this Special Issue (SI), papers on different subjects were published making a total of 14 contributions, 10 original research papers, and 4 review papers. The review paper of Ko et al. [1] provides a comprehensive overview of the significant advancements in engineered organ-on-a-chip research in a general way while in the review presented by Kanabekova and colleagues [2], a thorough analysis of microphysiological platforms used for modeling liver diseases can be found. To get a summary of the numerical models of microfluidic organ-on-a-chip devices developed in recent years, the review presented by Carvalho et al. [5] can be read. On the other hand, Maia et al. [6] report a systematic review of the diagnosis methods developed for COVID-19, providing an overview of the advancements made since the start of the pandemic. In the following, a brief summary of the research papers published in this SI will be presented, with organs-on-a-chip, microfluidic devices for detection, and device optimization having been identified as the main topics.info:eu-repo/semantics/publishedVersio

A platform to restore intra-tissue flow in live explant assays

Tissue resection during first-line surgery is a standard strategy in the clinic for several life-threatening diseases, such as cancer. In case of malignancy, despite the benefits from surgery, cancer often becomes treatment-resistant and metastasises, limiting therapeutic options and patient survival. Due to tumour heterogeneity, treatment personalisation can improve patient outcomes, however tools based on native tissue samples, used for patient-specific drug screening remain very limited. This is primarily due to the diffusion-limited mass transport in static culture conditions, where tissue viability is rapidly reduced due to ischemia. Our aim is to develop a platform that restores intra-tissue flow through native tissue specimens to prolong their preservation ex vivo. Flow of culture media around tissue specimens has been commonly used for sample preservation. However, the efficacy of most currently available platforms has been limited, as ex vivo specimen perfusion is not facilitated in these technologies. As fluid is allowed to travel around specimen periphery, intra-tissue flow is hydraulically disadvantaged and benefits from culture media renewal only affect cells within 200 μm from explant surface. In this thesis, a novel system is presented that comprises a channel-based device with a suitably-designed constriction to block peri-fusion (i.e. flow around the tissue) and facilitate specimen entrapment and perfusion. Using a syringe pump, device efficacy to facilitate intra-tissue flow was investigated, showing that the induced perfusion occurred through both the vasculature and the interstitium. The effects of perfusion on specimen maintenance and function were also investigated. It was showed that healthy mouse liver and cancerous mouse and human omental specimens were better preserved under perfused conditions in the developed apparatus for 48h. Intra-tissue flow was also effective to inhibit cell metabolism after a 2h-specimen perfusion with a metabolic poison, suggesting this system may have great potential for predictive, live explant assays.Open Acces

Metabolomic responses to acute exercise and AMPK-glycogen binding disruption in mice

Background: Exercise is widely accepted as a potent intervention to promote whole-body metabolic health and help prevent and/or treat metabolic diseases. Exercise represents a major challenge to energy homeostasis, both at the whole-body and cellular level. Numerous molecular metabolic responses to acute exercise are activated to preserve energy homeostasis. Central to maintaining cellular energy balance is the AMP-activated protein kinase (AMPK), a heterotrimeric enzyme that senses cellular energy levels by competitively binding to adenosine mono-, di- and triphosphate (AMP, ADP and ATP, respectively). In response to energy stress, AMPK becomes activated and switches on energy-producing catabolic processes while simultaneously switching off energy-consuming anabolic processes. Through its regulatory β subunit, AMPK also binds glycogen – an important energy reserve primarily stored in liver and skeletal muscle. Although growing evidence from AMPK double knock-in (DKI) mice has highlighted physiological consequences of disrupting AMPK-glycogen binding in exercise and metabolic control, the underlying molecular pathways and mechanisms remain unclear. Metabolomics is the unbiased collection and study of small molecules (< 1500 daltons) involved in metabolic reactions to capture molecular snapshots of metabolic pathways, for example associated with given stimuli (e.g., exercise) or genotype. Therefore, metabolomic analysis of biofluids and tissues represents a promising approach to better understand the molecular metabolic responses to acute exercise and the physiological effects of disrupting AMPK-glycogen binding in vivo. Methods: Plasma, gastrocnemius muscle and liver samples were collected from age-matched male WT and DKI mice with disrupted AMPK-glycogen binding at rest and immediately following 30-min submaximal treadmill running. An untargeted mass spectrometry-based metabolomic approach was utilised to determine changes in plasma and/or tissue metabolites occurring in response to acute exercise and the disruption of AMPK-glycogen interactions in DKI mice. Complementary whole-body mouse phenotyping and real-time metabolic phenotyping assays using the Seahorse XFe24 Analyzer and Oroboros O2k high-resolution respirometer were performed to compare energy metabolism and substrate utilisation profiles in mouse embryonic fibroblast (MEF) cells and skeletal muscle from WT and DKI mice. Results/Discussion: Relative to WT mice, DKI mice had reduced maximal running speed, concomitant with increased total body mass and adiposity. In plasma, a total of 83 metabolites were identified/annotated, with 17 metabolites significantly different in exercised versus rested mice. These included amino acids, acylcarnitines and steroid hormones. Distinct plasma metabolite profiles were observed between the rest and exercise conditions and between WT and DKI mice at rest, while metabolite profiles of both genotypes converged following exercise. These differences in metabolite profiles were primarily explained by exercise-associated increases in acylcarnitines and steroid hormones as well as decreases in amino acids and derivatives following exercise. DKI mice showed greater decreases in plasma amino acid levels following exercise versus WT. In liver and skeletal muscle, 150 and 92 metabolites were identified/annotated, respectively. Similar to the plasma metabolite responses observed across genotypes and conditions, significant overall metabolite profile shifts were observed between WT and DKI mice at rest, as well as significant metabolite profile differences between the rested and exercised conditions. Differential muscle metabolite responses to acute exercise were also observed between genotypes. Markers of mitochondrial respiration in permeabilised gastrocnemius fibres were not affected by AMPK DKI mutation, although there were reduced total ATP rate and relative contribution of glycolysis in DKI versus WT MEF cells. Conclusion: The plasma metabolomic analyses performed in Study 1 represent the first study to map mouse plasma metabolomic changes following acute exercise in WT mice and the effects of disrupting AMPK-glycogen interactions using DKI mice. Untargeted metabolomics uncovered alterations in plasma, skeletal muscle and liver metabolite profiles between rested and exercised mice in both genotypes, and between genotypes at rest. This study has uncovered known and previously unreported plasma metabolite responses to acute exercise in WT mice, as well as greater decreases in amino acids following exercise in DKI plasma. These mouse tissue metabolomic datasets, combined with cell and tissue respirometry data complement previous whole-body, tissue and molecular characterisation of WT and DKI mice, revealing potential metabolic pathways and novel molecular biomarkers underlying exercise’s metabolic health benefits and the physiological effects of disrupting AMPK-glycogen binding in mice

Imagerie IRTF tridimensionnelle pour l'étude de l'insuffisance rénale chronique

CKD (Chronic Kidney Disease) is one of the worst public diseases in developing countries. The stages of CKD are mainly based on measured or estimated GFR (Glomerular Filtration Rate). However, this method is not sensitive enough on early stages of the pathology and thus do not offer accurate diagnostic value. Early detection and treatment can often limit or avoid the chronicity effects of the disease. This thesis focuses on the development of FTIR microscopy as a diagnostic tool for the identification by histopathology at glomerulus level of the kidney in CKD model. We developed a technique of 3D reconstruction for the FTIR imaging of biochemical components changes in glomeruli for identifying the pathological marker of CKD. The curve-fitting and spectral clustering are applied on the FTIR microscopy analysis to distinguish between healthy and pathological glomeruli of a kidney. Then, the glomerular microvasculatureis highlighted to reveal the morphological abnormalities by perfusing contrast agents into blood vessels. With advanced 3D statistical methods and 3D image visualization by microscopy, FTIR spectro-imaging can be used as a functional technique to determine the morphological and molecular changes occurring along CKD development.L’insuffisance rénale chronique (IRC) et l’une des pires maladies chroniques dans les pays développés. Les grades de l’IRC sont principalement basés sur la mesure ou l’estimation du taux de filtration rénale (GFR). Cependant, cette méthode est peu sensible sur les premiers stades de la pathologie et n’apporte donc pas de valeur diagnostique. La détection de la pathologie à des stades précoces et son traitement peuvent éviter ou limiter les effets délétères de la chronicité. Cette thèse se penche sur le développement de la microscopie IRTF en tant qu’outil diagnostic pour l’identification par histopathologie à l’échelle du glomérule dans un modèle d’IRC. Nous avons développé la technique de reconstruction 3D pour l’imagerie IRTF des modifications biochimiques à l’échelle du glomérule pour déterminer des marqueurs de l’IRC. La déconvolution spectrale et le clustering sont appliqués après analyses IRTF pour distinguer les modèles sains et pathologiques. Ensuite, la microvasculature glomérulaire est révélée par agent de contraste pour en déterminer les anomalies morphologiques. Grâce aux résultats obtenus en 3D et l’utilisation de méthodes statistiques avancées, la microscopie IRTF est utilisée comme une technique fonctionnelle pour déterminer les modifications morphologiques et moléculaires apparaissant au cours du développement de l’IRC

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 247)

This bibliography lists 269 reports, articles and other documents introduced into the NASA scientific and technical information system in June 1983

Protein Structure

Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic