In-situ Self-Aligned NaCl-Solution Fluidic-Integrated Microwave Sensors for Industrial and Biomedical Applications

This work presents, for the first time, an in-situ self-aligned fluidic-integrated microwave sensor for characterizing NaCl contents in NaCl-aqueous solution based on a 16-GHz bandpass combline cavity resonator. The discrimination of the NaCl concentration is achievable by determining amplitude differences and resonant frequency translations between the incident and reflected microwave signals at the input terminal of the cavity resonator based on the capacitive loading effects of the comb structure inside the cavity introduced by the NaCl solution under test. Twelve NaCl-aqueous liquid mixture samples with different NaCl concentrations ranging from 0% to 20% (0 - 200 mg/mL), which are generally exploited in most industrial and biomedical applications, were prepared and encapsulated inside a Teflon tube performing as a fluidic channel. The Teflon tube is subsequently inserted into the cavity resonator through two small holes, fabricated through the sidewalls of the cavity, which can be used to automatically align the fluidic subsystem inside the combline resonator considerably easing the sensor setup. Based on at least five repeated measurements, the NaCl sensor can discriminate the NaCl content of as low as 1% with the measurement accuracy of higher than 96% and the maximum standard deviation of only 0.0578. There are several significant advantages achieved by the novel NaCl sensors, e.g. high accuracy, traceability and repeatability; ease of sensor setup and integration to actual industrial and biomedical systems enabling in-situ and real-time measurements; noninvasive and noncontaminative liquid solution characterization as well as superior sensor reusability due to a complete physical separation between the fluidic and microwave subsystems

Perancangan dan Simulasi Sensor Volume Zat Cair berbasis Metamaterial Rektangular

Pengukuran volume zat cair yang sensitif dapat dicapai menggunakan alat ukur atau sensor. Akan tetapi sensor volume zat cair tidak banyak mengembangkan, padahal pengukuran volume berdampak langsuang pada  nilai ekonomis, keberhasilan penelitian ilmiah,  dan kemanjuran dosis obat. Penelitian yang telah dilakukan hanya sebatas pada pengukuran pada kenaikan permukaan zat cair  dalam kenaikan tandon. menggunakan sensor fotodioda. Metamaterial telah banyak dikembangakan sebagai sistem sensor yang sensitif karena berbasis gelombang elektromagnetik, namun belum spesifik mengkajinya sebagai sensor volume zat cair. Tujuan penelitian ini adalah untuk merancang dan menyimulasikan penggunaan sensor metamaterial yang sensitif dalam pengukuran volume zat cair.  Sensor didesain dengan prinsip split ring resonator berbentuk rektangular (SRR-R) yang terdiri  dari cincin logam tembaga dan substrat FR4-Epoxy. Sensor SRR-R disimulasikan pada rentang frekuensi 350-850 MHz untuk mendeteksi perubahan volume zat cair (aquades, air tawar dan etanol) dari 5 - 44 ml. Hasil simulasi menunjukan terjadinya pergeseran frekuensi resonan spektrum S21 yang  jelas untuk masing-masing zat cair. Pergeseraan frekuensi resonan untuk sampel aquades terjadi pada frekuensi 403 – 527 MHz, air tawar 403 – 528 MHz, dan etanol 60 – 783 MHz. Distribusi medan E dan medan H menunjukan nilai maksimum sebesar 18662 V.  dan 43771 A. . Karakteristik kurva linier terjadi dalam rentang volume 12-44 ml untuk semua sampel zat cair. Sensor metamaterial SRR-R berhasil disimulasikan untuk mendeteksi perubahan volume zat cair dengan sensitivitas pengukuran aquades -1.3999 MHz/ml, air tawar -2.6833 MHz/ml, adan etanol -3.5685 MHz/ml

Broadband microwave permittivity measurements of blood for hydration monitoring.

PhD ThesisIn the UK, dehydration and malnutrition affects vulnerable patients, costing the NHS an estimated £13 billion. Whilst a patient’s hydration levels is usually determined by fluid balance or plasma osmolality methods, these have a slow turnaround time and are invasive. New approaches that are non-invasive, real-time and easy to use need to be developed to improve dehydration prevention. The present study modified an NPL broadband microwave permittivity system by inverting the dielectric probe to allow for the broadband permittivity measurement of microliter fluid samples. The system was extensively characterised using solutions of NaCl and pure water. While some calibration artifacts were introduced, overall the measured permittivity response was only 3% below the expected absolute permittivity. To determine if blood permittivity changed during dehydration, blood permittivity measurements were taken from healthy athletes (who cycled at a high intensity in a 35°C, 40% humidity environment for 80 min) and compared to changes in blood osmolality and body mass. We demonstrated a correlation existed between blood osmolality and permittivity at a range of frequencies, suggesting the technique has the potential to monitor hydration in sportspeople. Finally, to determine exactly which components were affecting the permittivity profile during dehydration, a range of NaCl, bovine HCT and BSA concentrations in physiological osmotic solutions were measured at frequencies between 0.5 GHz to 20 GHz using our inverted probe method. We demonstrated a strong linear correlation between the real and imaginary permittivity when varying concentrations of HCT, BSA and osmolality. However, while little difference was found between the frequency-permittivity profile of HCT and BSA for both the real and imaginary permittivity, significant difference existed compared to NaCl, with a window existing at 20 GHz where measurements could be made independent of NaCl. Overall microwave dielectric measurements were found to be suitable for measuring changes in blood hydration

Radio Frequency Micro/Nano-Fluidic Devices for Microwave Dielectric Property Characterizations

In this dissertation, a number of different topics in microwave dielectric property measurements have been covered by a systematic approach to the goals of development of dielectric spectroscopy and study of its high electric field effects with integrated on-chip microwave microfluidic / nanofluidic devices. A method of parasitic effects cancellation for dielectric property measurement is proposed, analyzed, and experimentally evaluated for microwave characterization of small devices and materials that yield low intensity signals. The method dramatically reduces parasitic effects to uncover the otherwise buried signals. A high-sensitive radio frequency (RF) device is then developed and fabricated to detect small dielectric property changes in microfluidic channel. Sensitivity improvement via on-chip transmission line loss compensation is then analyzed and experimentally demonstrated. Different samples are measured and high sensitivity is achieved compared to conventional transmission-line-based methods. High DC electric field effects on dielectric properties of water are investigated with microwave microfluidic devices. Gold microstrip-line-based devices and highly-doped silicon microstrip-line-based devices are exploited. Initiation process of water breakdown in a small gap is discussed. Electrode surface roughness is examined and its effect on observed water breakdown is investigated. It is believed that electrode surface roughness is one of critical factors for the initiation process of water breakdown in small gap system. Finally, water dielectric property subjected to uniform DC electric field in 260 nm planar microfluidic channels is experimentally studied via silicon microstrip-line-based devices. When applied DC field is as high as up to ~ 1 MV/cm, the water is sustained and no breakdown is occurred. Strong water dielectric saturation effects are observed from measured water dielectric spectroscopy. An on-chip, broadband microwave dielectric spectrometer with integrated transmission line and nanofluidic channels is designed, fabricated and characterized through microwave S-parameter measurements. Heavily-doped Si material is used to build the microstrip line to provide broadband characterization capability. 10 nm deep planar Si nanofluidic channels are fabricated through native oxide etch and wafer bonding process. It is the first effort to build the microstrip line with periodically loaded individual sub-10 nm nanofluidic channels to conduct the broadband high frequency characterization of materials within confined space. The functionality of the device is demonstrated by the measurement of DI water. It behaves well and has great potentials on the study of confinement effects of fluids and molecules. Further work includes development of parasitic signal de-embedding procedures for accurate measurements

Non-Invasive Blood Glucose Monitoring Using Electromagnetic Sensors

Monitoring glycemia levels in people with diabetes has developed rapidly over the last decade. A broad range of easy-to-use systems of reliable accuracies are now deployed in the market following the introduction of the invasive self-monitoring blood glucose meters (i.e., Glucometers) that utilize the capillary blood samples from the fingertips of diabetic patients. Besides, semi-invasive continuous monitors (CGM) are currently being used to quantify the glucose analyte in interstitial fluids (ISF) using an implantable needle-like electrochemical sensors. However, the limitations and discomforts associated with these finger-pricking and implantable point-of-care devices have established a new demand for complete non-invasive pain-free and low-cost blood glucose monitors to allow for more frequent and convenient glucose checks and thereby contribute more generously to diabetes care and prevention. Towards that goal, researchers have been developing alternative techniques that are more convenient, affordable, pain-free, and can be used for continuous non-invasive blood glucose monitoring. In this research, a variety of electromagnetic sensing techniques were developed for reliably monitoring the blood glucose levels of clinical relevance to diabetes using the non-ionizing electromagnetic radiations of no hazards when penetrating the body. The sensing structures and devices introduced in this study were designed to operate in specific frequency spectrums that promise a reliable and sensitive glucose detection from centimeter- to millimeter-wave bands. Particularly, three different technologies were proposed and investigated at the Centre for Intelligent Antenna and Radio Systems (CIARS): Complementary Split-Ring Resonators (CSRRs), Whispering Gallery Modes (WGMs) sensors, and Frequency-Modulated Continuous-Wave (FMCW) millimeter-Wave Radars. Multiple sensing devices were developed using those proposed technologies in the micro/millimeter-wave spectrums of interest. A comprehensive study was conducted for the functionality, sensitivity, and repeatability analysis of each sensing device. Particularly, the sensors were thoroughly designed, optimized, fabricated, and practically tested in the laboratory with the desired glucose sensitivity performance. Different topologies and configurations of the proposed sensors were studied and compared in sensitivity using experimental and numerical analysis tools. Besides, machine learning and signal processing tools were intelligently applied to analyze the frequency responses of the sensors and reliably identify different glucose levels. The developed glucose sensors were coupled with frequency-compatible radar boards to realize small mobile glucose sensing systems of reduced cost. The proposed sensors, beside their impressive detection capability of the diabetes-spectrum glucose concentrations, are endowed with favourable advantages of simple fabrication, low-power consumption, miniaturized compact sizing, non-ionizing radiation, and minimum health risk or impact for human beings. Such attractive features promote the proposed sensors as possible candidates for development as mobile, portable/wearable gadgets for affordable non-invasive blood glucose monitoring for diabetes. The introduced sensing structures could also be employed for other vital sensing applications such as liquid type/quantity identification, oil adulteration detection, milk quality control, and virus/bacteria detection. Another focus of this thesis is to investigate the electromagnetic behavior of the glucose in blood mimicking tissues across the microwave spectrum from 200 MHz to 67 GHz using a commercial characterization system (DAK-TL) developed by SPEAG. This is beneficial to locate the promising frequency spectrums that are most responsive to slight variations in glucose concentrations, and to identify the amount of change in the dielectric properties due to different concentrations of interest. Besides, the effect of the blood typing and medication was also investigated by measuring the dielectric properties of synthetic “artificial” as well as authentic “human” blood samples of different ABO-Rh types and with different medications. Measured results have posed for other factors that may impact the developed microwave sensors accuracy and sensitivity including the patient’s blood type, pre-existing medical conditions, or other illnesses

Development of paper-based analytical devices for particulate metals in welding fume

Includes bibliographical references.2015 Fall.Exposure to metal-containing particulate matter places a tremendous burden on human health. Studies show that exposures lead to cardiovascular disease, asthma, flu-like illnesses, other respiratory disorders, and to increased morbidity. Individuals who work in occupations such as metalworking, construction, transportation, and mining are especially susceptible to unsafe exposures because of their proximity to the source of particle generation. Despite the risk to worker health, relatively few are routinely monitored for their exposure due to the time-intensive and cost-prohibitive analytical methods currently employed. The current paradigm for chemical speciation of workplace pollution is outdated and inefficient. Paper-based microfluidic devices, a new type of sensor technology, are poised to overcome issues associated with chemical analysis of particulate matter, specifically the cost and timeliness of exposure assessment. Paper sensors are designed to manipulate microliter liquid volumes and because flow is passively driven by capillary action, analysis costs are very low. The objective of this work was to develop new technology for rapidly measuring Ni, Cu, Fe, and Cr in welding fume using easy-to-use paper devices. This dissertation covers the development of two techniques for quantifying metal concentration: spot integration and distance-based detection. Metal concentrations as low as 0.02 ppm are reported. A method for controlling reagent deposition as well as a new interface for multiplexed detection of metals, is discussed

Development of Microwave/Droplet-Microfluidics Integrated Heating and Sensing Platforms for Biomedical and Pharmaceutical Lab-on-a-Chip Applications

Interest in Lab-on-a-chip and droplet-based microfluidics has grown recently because of their promise to facilitate a broad range of scientific research and biological/chemical processes such as cell analysis, DNA hybridization, drug screening and diagnostics. Major advantages of droplet-based microfluidics versus traditional bioassays include its capability to provide highly monodispersed, well-isolated environment for reactions with magnitude higher throughput (i.e. kHz) than traditional high throughput systems, as well as its low reagent consumption and elimination of cross contamination. Major functions required for deploying droplet microfluidics include droplet generation, merging, sorting, splitting, trapping, sensing, heating and storing, among which sensing and heating of individual droplets remain great challenges and demand for new technology. This thesis focuses on developing novel microwave technology that can be integrated with droplet-based microfluidic platforms to address these challenges. This thesis is structured to consider both fundamentals and applications of microwave sensing and heating of individual droplets very broadly. It starts with developing a label-free, sensitive, inexpensive and portable microwave system that can be integrated with microfluidic platforms for detection and content sensing of individual droplets for high-throughput applications. This is, indeed, important since most droplet-based microfluidic studies rely on optical imaging, which usually requires expensive and bulky systems, the use of fluorescent dyes and exhaustive post-imaging analysis. Although electrical detection systems can be made inexpensive, label-free and portable, most of them usually work at low frequencies, which limits their applications to fast moving droplets. The developed microwave circuitry is inexpensive due to the use of off-the-shelf components, and is compact and capable of detecting droplet presence at kHz rates and droplet content sensing of biological materials such as penicillin antibiotic, fetal bovine serum solutions and variations in a drug compound concentration (e.g., for Alzheimer’s Disease). Subsequently, a numerical model is developed based on which parametrical analysis is performed in order to understand better the sensing and heating performance of the integrated platform. Specifically, the microwave resonator structure, which operates at GHz frequency affecting sensing performance significantly, and the dielectric properties of the microfluidic chip components that highly influence the internal electromagnetic field and energy dissipation, are studied systematically for their effects on sensing and heating efficiency. The results provide important findings and understanding on the integrated device operation and optimization strategies. Next, driven by the need for on-demand, rapid mixing inside droplets in many applications such as biochemical assays and material synthesis, a microwave-based microfluidic mixer is developed. Rapid mixing in droplets can be achieved within each half of the droplet, but not the entire droplet. Cross-center mixing is still dominated by diffusion. In this project, the microwave mixer, which works essentially as a resonator, accumulates an intensive, nonuniform electromagnetic field into a spiral capacitive gap (around 200 μm) over which a microchannel is aligned. As droplets pass by the gap region, they receive spatially non-uniform energy and thus have non-uniform temperature distribution, which induces non-uniform Marangoni stresses on the interface and thus three-dimensional (3D) chaotic motion inside the droplet. The 3D chaotic motion inside the droplet enables fast mixing within the entire droplet. The mixing efficiency is evaluated by varying the applied power, droplet length and fluid viscosity. In spite of various existing thermometry methods for microfluidic applications, it remains challenging to measure the temperature of individual fast moving droplets because they do not allow sufficient exposure time demanded by both fluorescence based techniques and resistance temperature detectors. A microwave thermometry method is thus developed here, which relies on correlating fluid temperature with the resonance frequency and the reflection coefficient of the microwave sensor, based on the fact that liquid permittivity is a function of temperature. It is demonstrated that the sensor can detect the temperature of individual droplets with ±1.2 °C accuracy. At the final part of the thesis, I extend my platform technology further to applications such as disease diagnosis and drug delivery. First, I develop a microfluidic chip for controlled synthesis of poly (acrylamide-co-sodium acrylate) copolymer hydrogel microparticles whose structure varies with temperature, chemical composition and pH values. This project investigates the effects of monomer compositions and cross-linker concentrations on the swelling ratio. The results are validated through the Fourier transform infrared spectra (FTIR), SEM and swelling test. Second, a preliminary study on DNA hybridization detection through microwave sensors for disease diagnosis is conducted. Gold sensors and biological protocols of DNA hybridization event are explored. The event of DNA hybridization with the immobilized thiol-modified ss-DNA oligos and complimentary DNA (c-DNA) are monitored. The results are promising, and suggests that microwave integrated Lab-on-a-chip platforms can perform disease diagnosis studies

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

Design and implementation of a microstrip filter biosensor for healthcare applications

PhD ThesisThe aim of this research was to develop high-frequency biosensors by a combination of traditional microstrip filters and microfluidics. Lowpass and bandpass microstrip filters were designed for operational frequencies less than 3 GHz. Analytical modelling was used to initially determine microstrip filter geometry and then 3D electromagnetic simulation software utilised to examine their performance. Once the design was optimised, devices were fabricated using traditional PCB manufacturing approaches and clean room evaporation techniques. The fabricated filters were compared with the simulation results. The characteristic filter features at 0.66 GHz, 0.80 GHz, and 1.60 GHz demonstrated good agreement to within 90% of the simulated models. Microfluidic reservoirs were then attached to the microstrip filters prior to biological testing. The targeted biomolecules for detection were prostate specific antigen (PSA). A vector network analyser was used to measure the S-parameters of the filters at each stage of functionalisation and immobilisation. Biosensor performance was assessed by measurement of the resonant amplitude and frequency shifts at the characteristic operational frequencies as a function of concentration of the immobilised PSA. The efficacy test of the produced biosensors demonstrated label-free detection down to a minimum analyte concentration of 6.125 ng/ml, this corresponding to an amplitude change of 9 dB and a frequency shift of 10 MHz in the characteristic feature of the S11 signal. This work has demonstrated the applicability of both lowpass and bandpass microstrip filters, with an operational frequency range less than 3 GHz and with suitably integrated microfluidics, to perform as biosensors. This is the first experimental assessment report of this type of radio frequency-based biosensor showing the real-time detection of PSA biomarkers

Investigation of the thermostability and activity of biomolecules in bio-friendly deep eutectic solvents

The solvent environment of a biomolecule is critical to its optimal performance in various scenarios, including biocatalysis, drug delivery, therapeutics, and biosensing. This dissertation mainly discusses the implementation of deep eutectic solvents (DESs) as an emerging and alternate solvent system for biomolecular applications, including aspects of protein thermostabilization and extraction and the role of DESs in biocatalytic systems, such as those involving lipases or whole cells. Additionally, a discussion of DESs for the modulation of nucleic acid systems, drug solubilization and delivery, and emerging biomedical applications is included. Overall, the intent of this dissertation is to elucidate some of the advantages of implementing DESs in an array of biomolecule-driven purposes and illustrate the versatility and potential of these unique, environmentally responsible solvents for next-generation biotechnological and biomedical applications.Includes bibliographical references