Diagnosis of glioma molecular markers by terahertz technologies

This review considers glioma molecular markers in brain tissues and body fluids, shows the pathways of their formation, and describes traditional methods of analysis. The most important optical properties of glioma markers in the terahertz (THz) frequency range are also presented. New metamaterial-based technologies for molecular marker detection at THz frequencies are discussed. A variety of machine learning methods, which allow the marker detection sensitivity and differentiation of healthy and tumor tissues to be improved with the aid of THz tools, are considered. The actual results on the application of THz techniques in the intraoperative diagnosis of brain gliomas are shown. THz technologies’ potential in molecular marker detection and defining the boundaries of the glioma’s tissue is discussed

Experimentation and Multiphysical Modeling of Bioanalytical Microdevices

Bioanalytics involves quantitative measurements of complex biological samples that contain metabolites, DNA, RNA, and proteins. Efficient sample preparation for downstream analysis and sensitive detection of analytes can be achieved via bioanalytical microdevices. Fully realizing the potential of these devices requires tool characterization and bioprocess optimization, in addition to understanding device physics. Therefore, this thesis introduces multiphysical modeling and experimentation of microdevices, with applications to diabetes care and single-cell analysis. To understand the physics of viscometric glucose microsensors, this thesis presents a model of the sensor, which couples the fluid flow with vibrating diaphragms. The model is used to predict the sensor response to glucose via theory of squeeze-film damping and vibrations of pre-stressed plate. A first-principle-based model resulting from the theory can be evaluated from the device's geometric and material properties, and quantitatively determines the device response to vibrational excitations at varying glucose concentrations. Next, this thesis introduces a theoretical model for viscometric glucose microsensors that employ harmonic microcantilever oscillation in the sensing liquid. The presented model associates the unsteady Stokes equation with the motion of a bounded viscous liquid to understand the hydrodynamic impact on the cantilever. With a proper consideration of the viscosity and bounded geometry of liquid media, the model relaxes the thin-film assumption required for the diaphragm-based model, enabling an accurate representation of fluid-structure interactions based on fundamental structural vibration and fluid flow equations. Next, this thesis presents an experimental exploration of a hydrogel-based affinity microsensor for glucose monitoring via dielectric measurements. The microsensor incorporates a synthetic hydrogel that is attached to the device surface via in situ polymerization, which eliminates mechanical moving parts required in the viscometric glucose sensors. Changes in the dielectric properties of the hydrogel when binding reversibly with glucose molecules have been measured using a MEMS capacitive transducer to determine the glucose concentration. Experimental results demonstrate that in a glucose concentration range of 0–500 mg/dL and with a resolution of 0.35 mg/dL or better, the microsensor exhibits a repeatable and reversible response, and can potentially be useful for continuous glucose monitoring in diabetes care. Additionally, this thesis presents a microfluidic preprocessing method that integrates single-cell picking, lysing, reverse transcription and digital polymerase chain reaction to enable the isolation, tracking and gene expression analysis at single-cell level for individual cells. The approach utilizes a photocleavable bead-based microfluidic device to synthesize and deliver stable complementary DNA for downstream gene expression analysis, thereby allowing chip-based integration of multiple reactions and facilitating the minimization of sample loss or contamination. Finally, this thesis ends with concluding remarks and directions of future work towards continuous glucose monitoring and high-throughput single-cell genetic analysis

ANISOTROPIC POLARIZED LIGHT SCATTER AND MOLECULAR FACTOR COMPUTING IN PHARMACEUTICAL CLEANING VALIDATION AND BIOMEDICAL SPECTROSCOPY

Spectroscopy and other optical methods can often be employed with limited or no sample preparation, making them well suited for in situ and in vivo analysis. This dissertation focuses on the use of a near-infrared spectroscopy (NIRS) and polarized light scatter for two such applications: the assessment of cardiovascular disease, and the validation of cleaning processes for pharmaceutical equipment.There is a need for more effective in vivo techniques for assessing intravascular disorders, such as aortic aneurysms and vulnerable atherosclerotic plaques. These, and other cardiovascular disorders, are often associated with structural remodeling of vascular walls. NIRS has previously been demonstrated as an effective technique for the analysis of intact biological samples. In this research, traditional NIRS is used in the analysis of aortic tissue samples from a murine knockout model that develops abdominal aortic aneurysms (AAAs) following infusion of angiotensin II. Effective application of NIRS in vivo, however, requires a departure from traditional instrumental principles. Toward this end, the groundwork for a fiber optic-based catheter system employing a novel optical encoding technique, termed molecular factor computing (MFC), was developed for differentiating cholesterol, collagen and elastin through intervening red blood cell solutions. In MFC, the transmission spectra of chemical compounds are used to collect measurements directly correlated to the desired sample information.Pharmaceutical cleaning validation is another field that can greatly benefit from novel analytical methods. Conventionally cleaning validation is accomplished through surface residue sampling followed by analysis using a traditional analytical method. Drawbacks to this approach include cost, analysis time, and uncertainties associated with the sampling and extraction methods. This research explores the development of in situ cleaning validation methods to eliminate these issues. The use of light scatter and polarization was investigated for the detection and quantification of surface residues. Although effective, the ability to discriminate between residues was not established with these techniques. With that aim in mind, the differentiation of surface residues using NIRS and MFC was also investigated

Selected Papers from the 1st International Electronic Conference on Biosensors (IECB 2020)

The scope of this Special Issue is to collect some of the contributions to the First International Electronic Conference on Biosensors, which was held to bring together well-known experts currently working in biosensor technologies from around the globe, and to provide an online forum for presenting and discussing new results. The world of biosensors is definitively a versatile and universally applicable one, as demonstrated by the wide range of topics which were addressed at the Conference, such as: bioengineered and biomimetic receptors; microfluidics for biosensing; biosensors for emergency situations; nanotechnologies and nanomaterials for biosensors; intra- and extracellular biosensing; and advanced applications in clinical, environmental, food safety, and cultural heritage fields

A Comprehensive Review on Food Applications of Terahertz Spectroscopy and Imaging.

Food product safety is a public health concern. Most of the food safety analytical and detection methods are expensive, labor intensive, and time consuming. A safe, rapid, reliable, and nondestructive detection method is needed to assure consumers that food products are safe to consume. Terahertz (THz) radiation, which has properties of both microwave and infrared, can penetrate and interact with many commonly used materials. Owing to the technological developments in sources and detectors, THz spectroscopic imaging has transitioned from a laboratory-scale technique into a versatile imaging tool with many practical applications. In recent years, THz imaging has been shown to have great potential as an emerging nondestructive tool for food inspection. THz spectroscopy provides qualitative and quantitative information about food samples. The main applications of THz in food industries include detection of moisture, foreign bodies, inspection, and quality control. Other applications of THz technology in the food industry include detection of harmful compounds, antibiotics, and microorganisms. THz spectroscopy is a great tool for characterization of carbohydrates, amino acids, fatty acids, and vitamins. Despite its potential applications, THz technology has some limitations, such as limited penetration, scattering effect, limited sensitivity, and low limit of detection. THz technology is still expensive, and there is no available THz database library for food compounds. The scanning speed needs to be improved in the future generations of THz systems. Although many technological aspects need to be improved, THz technology has already been established in the food industry as a powerful tool with great detection and quantification ability. This paper reviews various applications of THz spectroscopy and imaging in the food industry

Bioimaging with photonic crystal enhanced microscopy

The work presented in this dissertation addresses the optimization and application of a newly developed imaging modality, named photonic crystal enhanced microscopy (PCEM) for label-free detection of the surface attached biological samples. Photonic crystal, supporting guided-mode resonances and providing local optical modes, can enhance the light-matter interaction on its surface and thus used for label-free detection and biosensing. One dimensional photonic crystal surfaces are designed and utilized as a biosensor, and further integrated with an ordinary bright-field microscope. To demonstrate the validity of the photonic crystal biosensor, a three-dimensional modeling is developed and evaluated with finite-difference time-domain (FDTD) algorithm to predict and visualize the electromagnetic field redistribution upon the device surface. Applications of the photonic crystal enhanced microscopy are carried out for live cell imaging, nanoparticle detection and protein-protein binding detection. First, labelfree detection for live cell with PCEM imaging system is performed. Three different cellular phenomena are involved in this study, including cell adhesion, cell migration and stem cell differentiation. A novel imaging analysis software is developed to dynamically track the cell plasma membrane evolution. This traction software reveals mass redistribution with high resolution during cell migration which is previously difficult to evaluate quantitatively. Furthermore, both dielectric and metallic nanoparticles are examined and proved to be detectable as label-free detection using PCEM imaging system. Another novel imaging analysis software is developed to automatically count the number of nanoparticles attached on the sensor surface within the imaging field of view. Finally, a newly developed detection modality for protein-protein binding is demonstrated through PCEM imaging system using nanoparticle as tags. This new detection modality can avoid the photobleach problem and may also hold the potential to detect ultra-low concentrations of protein in the future. In summary, photonic crystal biosensor and its associated imaging system with microscopy developed in this work show great promise to the label-free biosensing and bioimaging. Future work will extend the application of PCEM to broader research and application fields served as the next generation sensing modalities

Biosensors for Diagnosis and Monitoring

Biosensor technologies have received a great amount of interest in recent decades, and this has especially been the case in recent years due to the health alert caused by the COVID-19 pandemic. The sensor platform market has grown in recent decades, and the COVID-19 outbreak has led to an increase in the demand for home diagnostics and point-of-care systems. With the evolution of biosensor technology towards portable platforms with a lower cost on-site analysis and a rapid selective and sensitive response, a larger market has opened up for this technology. The evolution of biosensor systems has the opportunity to change classic analysis towards real-time and in situ detection systems, with platforms such as point-of-care and wearables as well as implantable sensors to decentralize chemical and biological analysis, thus reducing industrial and medical costs. This book is dedicated to all the research related to biosensor technologies. Reviews, perspective articles, and research articles in different biosensing areas such as wearable sensors, point-of-care platforms, and pathogen detection for biomedical applications as well as environmental monitoring will introduce the reader to these relevant topics. This book is aimed at scientists and professionals working in the field of biosensors and also provides essential knowledge for students who want to enter the field