A Novel Investigation Method for the S21 Detection Circuit

This research proposes a novel method to investigate the performance of the S21 detection circuit. Aiming at low frequencies or DC, the method serves as an efficient way of verification and enjoys the benefit of low testing costs. The novel investigation method is demonstrated at 50 MHz and verified by the scattering parameters at 11.05 GHz. Based on the investigation, a model of process variations is constructed. The length of the interface paths is estimated by the model to be 63µm, which is consistent with the corresponding length of 74.6µm in the layout. For the measured phase and magnitude, the model indicates that the process variations in the device under test cause errors of 18.91% and 1.27%, whereas those in the interface paths lead to errors of 1.83% and 1%. Based on the model, practical recommendations are also proposed to further improve the measurement precision in the future

MEMS Technology for Biomedical Imaging Applications

Biomedical imaging is the key technique and process to create informative images of the human body or other organic structures for clinical purposes or medical science. Micro-electro-mechanical systems (MEMS) technology has demonstrated enormous potential in biomedical imaging applications due to its outstanding advantages of, for instance, miniaturization, high speed, higher resolution, and convenience of batch fabrication. There are many advancements and breakthroughs developing in the academic community, and there are a few challenges raised accordingly upon the designs, structures, fabrication, integration, and applications of MEMS for all kinds of biomedical imaging. This Special Issue aims to collate and showcase research papers, short commutations, perspectives, and insightful review articles from esteemed colleagues that demonstrate: (1) original works on the topic of MEMS components or devices based on various kinds of mechanisms for biomedical imaging; and (2) new developments and potentials of applying MEMS technology of any kind in biomedical imaging. The objective of this special session is to provide insightful information regarding the technological advancements for the researchers in the community

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

Diagnostic Biosensors for Detection of Blood-Derived Biomarkers

Standard diagnostic tools used from patient samples, specifically from blood draws, require specialized equipment, personnel, and facilities. Conventional techniques can often be very laborious and time consuming due to required sample preparation. The evident delay from sample collection to a patient’s result immensely impacts their outcome. The aims of this research are to design diagnostic biosensors that decrease time-to-results, minimize reagent and sample handling, and incorporate automated simple optical transduction and user interfaces for the detection of blood-derived biomarkers. Specifically, four biosensing detection mechanisms performed on 3 different point-of-care platforms will be discussed. First is a static loop-mediated isothermal amplification (LAMP) of nucleic acid aqueous droplet on a silicone chip platform immersed in mineral oil. The target-of-interest is a nucleic acid sequence as a biomarker for antibiotic resistant bacteria. The biosensing technique used related changes in interfacial tension (IFT) at the water-oil interface by measuring the change in contact angle (geometrical-effects) over time. Initially the system was characterized as a linear response in relation to concentration of bacteria in a buffer system down to the limit of detection (LOD) of 100 CFU per uL. Subsequently, with the addition of bacterial infected blood sample models, the system became a binary assay (i.e. yes or no) as low as 10 CFU per uL within 10 min of reaction. Secondly, a two-layered, paper microfluidic chip was utilized to quantify cancer cells from a buffy coat sample matrix by two detection mechanisms: 1) on-chip particle enumeration via smartphone microscope and 2) capillary flow dynamics via smartphone video processing. The assay resulted in a LOD as low as 1 cell per uL for the on-chip imaging aspect of platform and 0.1 cell per uL for the capillary flow analysis within 13 to 22s post application of blood sample. Lastly, the same concepts previously described in the first platform utilizes changes in IFT due to amplicon presence in an aqueous solution immersed in mineral oil. An emulsion LAMP platform was investigated to determine the relation between angle-dependent light scatter intensity (based off Mie scatter theory) and nucleic acid amplification progression. The phenomenon attributing to changes in light scatter intensities is due to the interfacial changes occurring in the emulsion droplets, where amplicon amount increases the IFT decreases, resulting in smaller diameter emulsions. Changes in light scatter intensity within 3 min of the reaction shows statistical difference in comparison to no target control (NTC) for 10^3 CFU per uL of bacteria dosed into aqueous sample. These four detection mechanisms and three platforms offer but a few alternatives as biosensing methods for blood-derived diagnostic biosensors

TARGETING MAGNETIC NANOCARRIERS IN THE HEAD FOR DRUG DELIVERY AND BIOSENSING APPLICATIONS

Magnetic nanocarriers have proven to be effective vehicles for transporting therapeutic and diagnostic agents in the body. Their main advantage is their ability to be manipulated by external magnets to direct them to specific targets in the body. In this dissertation, I study the transport, safety and efficacy of moving drug coated magnetic nanocarriers in different types of tissue. Movement of magnetic nanocarriers of sizes ranging from 100 nm to 1µm with different biocompatible coatings (Starch, PEG, Lipid and Chitosan) was quantified in different tissue types using an automated cryostat system. The safety of moving magnetic nanocarriers in live rodent brain tissue was assessed using electrophysiology, calcium imaging and immunohistochemistry. Moving magnetic nanocarriers in brain tissue did not significantly affect the firing ability of single neurons, synaptic connectivity and the overall functioning of the neuron network. As part of efficacy studies, steroid-eluting magnetic nanoparticles were targeted using external magnets to the inner ear of mice to counter hearing loss caused by cisplatin chemotherapeutics. This targeted steroid delivery to the cochlea significantly reduced the change in hearing threshold at 32 KHz caused by cisplatin injections and protected the hair cells from significant damage. Finally, I explore the potential of spin-transfer torque nano-oscillators, which are multi-layered ferromagnetic nanocarriers, as high-resolution in vivo wireless biosensors. These nanocarriers have been shown to detect action potentials from crayfish lateral giant neurons and that the microwave magnetic signals from these devices can be detected wirelessly by near field induction

Lab-on-a-Chip Fabrication and Application

The necessity of on-site, fast, sensitive, and cheap complex laboratory analysis, associated with the advances in the microfabrication technologies and the microfluidics, made it possible for the creation of the innovative device lab-on-a-chip (LOC), by which we would be able to scale a single or multiple laboratory processes down to a chip format. The present book is dedicated to the LOC devices from two points of view: LOC fabrication and LOC application

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

COMPUTATIONAL ANALYSIS OF CODE-MULTIPLEXED COULTER SENSOR SIGNALS

Nowadays, lab-on-a-chip (LoC) technology has been applied in a variety of applications because of its capability to perform accurate microscale manipulations of cells for point-of-care diagnostics. On the other hand, such a result is not readily available from an LoC device and typically still requires a post-inspection of the chip using traditional laboratory equipment such as a microscope, negating the advantages of the LoC technology. To solve this dilemma, my doctoral research mainly focuses on developing portable and disposable biosensors for interfacing with and digitizing the information from an LoC system. Our sensor platform, integrated with multiple microfluidic impedance sensors, electrically monitors and tracks manipulated cells on an LoC device. The sensor platform compresses information from each sensor into a 1-dimensional electrical waveform, and therefore, further signal processing is required to recover the readout of each sensor and extract information of detected cells. Furthermore, with the capability of the sensor platform, we have introduced integrated microfluidic cytometers to characterize properties of cells such as cell surface expression and mechanical properties.Ph.D

Integrated Gallium Phosphide Photonics

The integration of new materials mediating light-matter interaction in nanoscale devices is a persistent goal in nanophotonics. One of these materials is Gallium phosphide, which offers an attractive combination of a high refractive index (n=3.05 at a wavelength of 1550 nm) and a large bandgap (Eg =2.26 eV), enabling photonic devices with strongly confined light fields, not suffering from heating due to two-photon absorption at telecommunication wavelengths. Furthermore, due to its non-centrosymmetric crystal structure, it has a non-vanishing second-order susceptibility and is piezoelectric. Related to its large refractive index is a high third-order susceptibility. Prior to this work the use of GaP for photonic devices was limited to individual non-integrated components, as GaP was not available on a substrate with substantially lower refractive index equivalent to SOI-wafers for silicon. In this work a process was developed that allows the integration of GaP devices onto SiO2. It exploits direct wafer bonding of a GaP/AlxGa1-xP/GaP heterostructure onto a SiO2-on-Si wafer. After substrate removal, photonic devices are patterned by dry-etching in the top GaP device layer. The GaP devices investigated here are used to explore nonlinear optics and optomechanics. In the area of nonlinear optics, second- and third-harmonic generation are observed. The Kerr coefficient is experimentally estimated as n2[1550nm] = 1.2(5)x10^17m^2/W, for the first time in a precision measurement at telecommunication wavelengths. Four-wave mixing is used for broadband frequency comb generation, where a power threshold as low as 3 mW is obtained. The combination of four-wave mixing and second-harmonic generation leads to frequency-doubled combs. The optomechanical properties of GaP one-dimensional photonic crystal cavities are optimized by simulations and fabricated devices are characterized. Optical quality factors of Qo>10^5 and optomechanical coupling strengths of g0/2pi=400 kHz are measured. Dynamical backaction in the form of the spring effect and the parametric amplification are observed, as well as optomechanically induced transparency and absorption. A device design for a microwave-to-optical transducer is developed, relying on the piezoelectricity of GaP. It combines electromechanical and optomechanical transduction. The predicted electromechanical coupling strength is in the MHz range. Furthermore, photonic crystal cavity designs containing a slot at the center of the cavity are studied. According to simulations for slot widths below 30 nm, optomechanical coupling strengths g0/2pi>1 MHz could be achieved. Fabricated silicon photonic crystal cavities show high quality factors of Qo=8x10^4 while hosting a mechanical eigenmode with a frequency of 2.7 GHz. Because of process technology limitations, only slot widths as narrow as 40 nm can be fabricated, the achieved g0/2pi is limited to 300 kHz. The new GaP-on-insulator material platform opens the door to integrated GaP devices. Frequency combs are of interest for soliton comb formation, mid-IR frequency combs, and ultra-broadband supercontinuum generation. Microwave-to-optical transducers are on the one hand desired for quantum information processing, on the other hand they are applicable as efficient modulators or detectors for classical signals