SURFACE ENHANCED RAMAN SPECTROSCOPY (SERS) AS AN APPROACH FOR THE EMERGING LIQUID BIOPSY DIAGNOSTICS

Large Molecule bioanalysis and biosensor development are essential techniques that are required in many applications, including biotherapeutic development, in vitro diagnostic, biomarker detection, and early detection. These techniques should be highly specific and sensitive enough to identify and quantify an analyte of interest with minimum sample pretreatment requirements. This work explores the development and application of chip-scale bioassays based on surface-enhanced Raman scattering (SERS). It introduces sensing techniques to quantify various disease biomarkers, specifically pancreatic cancer. Blood is the best source of information about our body\u27s function. There are many biomarkers in the blood, and each biomarker\u27s high expression level can be referred to as a specific disorder. In this work, we have developed sensitive detecting methods to quantify these biomarkers. We successfully validated this method with human serum samples. Due to its capability to detect multiple biomarkers, the proposed bioanalytical technique can enhance the specificity of the approach enabled by machine learning based data classification algorithm

Multiplexed immunosensors for point-of-care diagnostic applications

Accurate, reliable, and cost-effective immunosensors are clinically important for the early diagnosis and monitoring of progressive diseases, and multiplexed sensing is a promising strategy for the next generation of diagnostics. This strategy allows for the simultaneous detection and quantification of multiple biomarkers with significantly enhanced reproducibility and reliability, whilst requiring smaller sample volumes, fewer materials, and shorter average analysis time for individual biomarkers than individual tests. In this opinionated review, we compare different techniques for the development of multiplexed immunosensors. We review the state-of-the-art approaches in the field of multiplexed immunosensors using electrical, electrochemical, and optical methods. The barriers that prevent translating this sensing strategy into clinics are outlined together with the potential solutions. We also share our vision on how multiplexed immunosensors will continue their evolution in the coming years

Recent Progress in Optical Sensors for Biomedical Diagnostics

In recent years, several types of optical sensors have been probed for their aptitude in healthcare biosensing, making their applications in biomedical diagnostics a rapidly evolving subject. Optical sensors show versatility amongst different receptor types and even permit the integration of different detection mechanisms. Such conjugated sensing platforms facilitate the exploitation of their neoteric synergistic characteristics for sensor fabrication. This paper covers nearly 250 research articles since 2016 representing the emerging interest in rapid, reproducible and ultrasensitive assays in clinical analysis. Therefore, we present an elaborate review of biomedical diagnostics with the help of optical sensors working on varied principles such as surface plasmon resonance, localised surface plasmon resonance, evanescent wave fluorescence, bioluminescence and several others. These sensors are capable of investigating toxins, proteins, pathogens, disease biomarkers and whole cells in varied sensing media ranging from water to buffer to more complex environments such as serum, blood or urine. Hence, the recent trends discussed in this review hold enormous potential for the widespread use of optical sensors in early-stage disease prediction and point-of-care testing devices.DFG, 428780268, Biomimetische Rezeptoren auf NanoMIP-Basis zur Virenerkennung und -entfernung mittels integrierter Ansätz

High-impedence NbSi TES sensors for studying the cosmic microwave background radiation

Precise measurements of the cosmic microwave background (CMB) are crucial in cosmology, because any proposed model of the universe must account for the features of this radiation. Of all CMB measurements that the scientific community has not yet been able to perform, the CMB B-mode polarization is probably the most challenging from the instrumental point of view. The signature of primordial gravitational waves, which give rise to a B-type polarization, is one of the goals in cosmology today and amongst the first objectives in the field. For this purpose, high-performance low-temperature bolometric cameras, made of thousands of pixels, are currently being developed by many groups, which will improve the sensitivity to B-mode CMB polarization by one or two orders of magnitude compared to the Planck satellite HFI detectors. We present here a new bolometer structure that is able to increase the pixel sensitivities and to simplify the fabrication procedure. This innovative device replaces delicate membrane-based structures and eliminates the mediation of phonons: the incoming energy is directly captured and measured in the electron bath of an appropriate sensor and the thermal decoupling is achieved via the intrinsic electron-phonon decoupling of the sensor at very low temperature. Reported results come from a 204-pixel array of Nb$_{x}$Si$_{1-x}$ transition edge sensors with a meander structure fabricated on a 2-inch silicon wafer using electron-beam co-evaporation and a cleanroom lithography process. To validate the application of this device to CMB measurements, we have performed an optical calibration of our sample in the focal plane of a dilution cryostat test bench. We have demonstrated a light absorption close to 20% and an NEP of about 7$\times10^{-16}$ W/$\sqrt{Hz}$, which is highly encouraging given the scope for improvement in this type of detectors.Comment: 6 pages, 10 figures. arXiv admin note: text overlap with arXiv:1005.0555 by other author

Plasmomechanical Systems: Principles and Applications

AbstractExtreme confinement of electromagnetic waves and mechanical displacement fields to nanometer dimensions through plasmonic nanostructures offers unprecedented opportunities for greatly enhanced interaction strength, increased bandwidth, lower power consumption, chip‐scale fabrication, and efficient actuation of mechanical systems at the nanoscale. Conversely, coupling mechanical oscillators to plasmonic nanostructures introduces mechanical degrees of freedom to otherwise static plasmonic structures thus giving rise to the generation of extremely large resonance shifts even for minor position changes. This nanoscale marriage of plasmonics and mechanics has led to the emergence of a new field of study called plasmomechanics that explores the fundamental principles underneath the coupling between light and plasmomechanical nanoresonators. In this review, both the fundamental concepts and applications of plasmomechanics as an emerging field of study are discussed. After an overview of the basic principles of plasmomechanics, the active tuning mechanisms of plasmonic nano‐mechanical systems are extensively analyzed. Moreover, the recent developments on the practical implications of plasmomechanic systems for such applications as biosensing and infrared detection are highlighted. Finally, an outlook on the implications of the plasmomechanical nanosystems for development of point‐of‐care diagnostic devices that can help early and rapid detection of fatal diseases are forwarded

Magnetic Resonance Imaging of Susceptibility Effects in Carotid Atherosclerosis

This thesis explores the use of susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM), to characterize carotid artery plaques with and without the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle contrast agents. The overall hypothesis is that QSM can serve to differentiate carotid artery plaque features of different susceptibility and provide a positive contrast mechanism for imaging the uptake of USPIOs. Chapter 1 describes the pathophysiology of carotid atherosclerosis. Vulnerable plaques, i.e. those at risk of rupture, can be characterized by the presence of a lipid rich necrotic core (LRNC), intraplaque haemorrhage (IPH), and inflammation. In addition, plaques may develop calcifications that may be protective of rupture. The chapter describes the established multi-contrast imaging protocols used for characterizing plaques. Furthermore, the use of USPIO-contrast agents to image inflammation is described. Chapter 2 describes the physical principles of MR image generation including the sensitivity to magnetic susceptibility. The principles of T2*w imaging, and susceptibility weighted imaging (SWI) are explained. Chapter 3 reviews the principles and post-processing steps involved in commonly used algorithms for QSM in terms of the underlying physical and mathematical principles which are then demonstrated in the form of numerical simulations. Chapter 4 presents the application of SWI to a group of patients who underwent USPIO enhanced MRI on a 1.5T MRI system. Images were acquired prior to infusion and 48 hours post infusion. SWI and gradient echo phase images were used to depict the field inhomogeneities generated by diamagnetic and paramagnetic materials within the plaques, calcification and USPIO-uptake. These results were then compared to a conventional carotid multi-contrast protocol, which includes R2*-mapping and T2*w imaging, and, where available, CT and histology. In chapter 5 QSM is performed in the carotid artery wall of a cohort of normal volunteers on a 1.5T MRI system. Unlike the brain, the neck contains fat which can cause severe errors in the field estimate, which propagate into the susceptibility map. Therefore, QSM was combined with water-fat separation for application in the neck to correct for these artifacts. This correctly estimated a high fat-fraction in fatty tissue in the neck and allowed for a detailed depiction of the anatomy of healthy volunteers. The susceptibility value measured in fatty tissue agreed with literature values. Chapter 6 applies QSM with water-fat separation to a subset of the patient group on a 1.5T MRI system. On pre-contrast scans QSM successfully identified calcification as diamagnetic tissue and the water-fat separation identified a lipid core. On the post-contrast susceptibility maps, USPIO-uptake was identified as hyperintense signal. This allows QSM to provide quantitative contrast in carotid imaging that can identify multiple features simultaneously and to simplify the imaging of USPIO-contrast. The results were confirmed using the multi-contrast carotid MRI protocol and, where available, histology and CT. Chapter 7 discusses the limitations of the current studies and the potential future improvements of the current methodology in terms of MR acquisition, post-processing algorithms and MR protocols. Future studies could serve to further evaluate the potential of QSM in carotid imaging and use it as a novel tool to quantify USPIO uptake in atherosclerotic carotid arteries

Surface-Enhanced Raman Scattering-Based Immunoassay Technologies for Detection of Disease Biomarkers

Detection of biomarkers is of vital importance in disease detection, management, and monitoring of therapeutic efficacy. Extensive efforts have been devoted to the development of novel diagnostic methods that detect and quantify biomarkers with higher sensitivity and reliability, contributing to better disease diagnosis and prognosis. When it comes to such devastating diseases as cancer, these novel powerful methods allow for disease staging as well as detection of cancer at very early stages. Over the past decade, there have been some advances in the development of platforms for biomarker detection of diseases. The main focus has recently shifted to the development of simple and reliable diagnostic tests that are inexpensive, accurate, and can follow a patient’s disease progression and therapy response. The individualized approach in biomarker detection has been also emphasized with detection of multiple biomarkers in body fluids such as blood and urine. This review article covers the developments in Surface-Enhanced Raman Scattering (SERS) and related technologies with the primary focus on immunoassays. Limitations and advantages of the SERS-based immunoassay platform are discussed. The article thoroughly describes all components of the SERS immunoassay and highlights the superior capabilities of SERS readout strategy such as high sensitivity and simultaneous detection of a multitude of biomarkers. Finally, it introduces recently developed strategies for in vivo biomarker detection using SERS

Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

Novel MRI Technologies for Structural and Functional Imaging of Tissues with Ultra-short T₂ Values

Conventional MRI has several limitations such as long scan durations, motion artifacts, very loud acoustic noise, signal loss due to short relaxation times, and RF induced heating of electrically conducting objects. The goals of this work are to evaluate and improve the state-of-the-art methods for MRI of tissue with short T₂, to prove the feasibility of in vivo Concurrent Excitation and Acquisition, and to introduce simultaneous electroglottography measurement during functional lung MRI

A review of advances in pixel detectors for experiments with high rate and radiation

The Large Hadron Collider (LHC) experiments ATLAS and CMS have established hybrid pixel detectors as the instrument of choice for particle tracking and vertexing in high rate and radiation environments, as they operate close to the LHC interaction points. With the High Luminosity-LHC upgrade now in sight, for which the tracking detectors will be completely replaced, new generations of pixel detectors are being devised. They have to address enormous challenges in terms of data throughput and radiation levels, ionizing and non-ionizing, that harm the sensing and readout parts of pixel detectors alike. Advances in microelectronics and microprocessing technologies now enable large scale detector designs with unprecedented performance in measurement precision (space and time), radiation hard sensors and readout chips, hybridization techniques, lightweight supports, and fully monolithic approaches to meet these challenges. This paper reviews the world-wide effort on these developments.Comment: 84 pages with 46 figures. Review article.For submission to Rep. Prog. Phy