Towards Bio-impedance Based Labs: A Review

In this article, some of the main contributions to BI (Bio-Impedance) parameter-based systems for medical, biological and industrial fields, oriented to develop micro laboratory systems are summarized. These small systems are enabled by the development of new measurement techniques and systems (labs), based on the impedance as biomarker. The electrical properties of the life mater allow the straightforward, low cost and usually non-invasive measurement methods to define its status or value, with the possibility to know its time evolution. This work proposes a review of bio-impedance based methods being employed to develop new LoC (Lab-on-a-Chips) systems, and some open problems identified as main research challenges, such as, the accuracy limits of measurements techniques, the role of the microelectrode-biological impedance modeling in measurements and system portability specifications demanded for many applications.Spanish founded Project: TEC 2013-46242-C3-1-P: Integrated Microsystem for Cell Culture AssaysFEDE

Screen-printed electrodes: Transitioning the laboratory in-to-the field

This short article overviews the use of screen-printed electrodes (SPEs) in the field of electroanalysis and compares their application against traditional laboratory based analytical techniques. Electroanalysis coupled with SPEs can offer low-cost, precise, sensitive, rapid, quantitative information and laboratory equivalent results. The combined use of SPEs and electroanalysis reduces the need of sample transportation and preparation to a centralised laboratory allowing experimentalists to perform the measurements where they are needed the most. We first introduce the basic concepts and principles of analytical techniques to the reader, with particular attention to electroanalysis, and then discuss the application of SPEs to common analytical targets such as food, environmental, forensics, cancer biomarkers and pathogenic monitoring and sensing

Implanted Antennas for Biomedical Applications

Body-Centric Wireless Communication (BCWC) is a central topic in the development of healthcare and biomedical technologies. Increasing healthcare quality, in addition to the continuous miniaturisation of sensors and the advancement in wearable electronics, embedded software, digital signal processing and biomedical technologies, has led to a new era of biomedical devices and increases possibility of continuous monitoring, diagnostic and/or treatment of many diseases. However, the major difference between BCWC, particularly implantable devices, and conventional wireless systems is the radio channel over which the communication takes place. The human body is a hostile environment from a radio propagation perspective. This environment is a highly lossy and has a high effect on the antenna elements, the radio channel parameters and, hence a dramatic drop in the implanted antenna performance. This thesis focuses on how to improve the gain of implanted antennas. In order to improve the gain and performance of implanted antennas, this thesis uses a combination of experimental and electromagnetic numerical investigations. Extensive simulation and experimental investigations are carried out to study the effects of various external elements on the performance improvement of implanted antennas. The thesis also shows the design, characterisation, simulation and measurements of four different antennas to work at ISM band and seventeen different scenarios for body wireless communication. A 3- layer (skin, fat and muscle) and a liquid homogenise phantom were used for human body modelling in both simulation and measurements. The results shows that a length of printed line and a grid can be used on top of the human skin in order enhance the performance of the implanted antennas. Moreover, a ring and a hemispherical lens can be used externally in order to enhance the performance of the implanted antenna. This approach yields a significant improvement in the antenna gain and reduces the specific absorption rate (SAR) in most cases and the obtained gain varies between 2 dB and 8 dB

A Multiplexing Immunosensor for the Quantification of Cytokine Biomarkers

abstract: Biosensors offer excellent diagnostic methods through precise quantification of bodily fluid biomarkers and could fill an important niche in diagnostic screening. The long term goal of this research is the development of an impedance immunosensor for easy-to-use, rapid, sensitive and selective simultaneously multiplexed quantification of bodily fluid disease biomarkers. To test the hypothesis that various cytokines induce empirically determinable response frequencies when captured by printed circuit board (PCB) impedance immunosensor surface, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used to test PCB biosensors versus multiple cytokine biomarkers to determine limits of detection, background interaction and response at all sweep frequencies. Results indicated that sensors for cytokine Interleukin-12 (IL-12) detected their target over three decades of concentration and were tolerant to high levels of background protein. Further, the hypothesis that cytokine analytes may be rapidly detected via constant frequency impedance immunosensing without sacrificing undue sensitivity, CV, EIS, impedance-time (Zt) methods and modeling were used to test CHITM gold electrodes versus IL-12 over different lengths of time to determine limits of detection, detection time, frequency of response and consistent cross-platform sensor performance. Modeling and Zt studies indicate interrogation of the electrode with optimum frequency could be used for detection of different target concentrations within 90 seconds of sensor exposure and that interrogating the immunosensor with fixed, optimum frequency could be used for sensing target antigen. This informs usability of fixed-frequency impedance methods for biosensor research and particularly for clinical biosensor use. Finally, a multiplexing impedance immunosensor prototype for quantification of biomarkers in various body fluids was designed for increased automation of sample handling and testing. This enables variability due to exogenous factors and increased rapidity of assay with eased sensor fabrication. Methods were provided for simultaneous multiplexing through multisine perturbation of a sensor, and subsequent data processing. This demonstrated ways to observe multiple types of antibody-antigen affinity binding events in real time, reducing the number of sensors and target sample used in the detection and quantification of multiple biomarkers. These features would also improve the suitability of the sensor for clinical multiplex detection of disease biomarkers.Dissertation/ThesisPh.D. Bioengineering 201

A Rapid and Ultra-sensitive Biosensing Platform based on Tunable Dielectrophoresis for Robust POC Applications

With the ongoing pandemic, there have been increasing concerns recently regarding major public health issues such as abuse of organophosphorus compounds, pathogenic bacterial infections, and biosecurity in agricultural production. Biosensors have long been considered a kernel technology for next-generation diagnostic solutions to improve food safety and public health. Significant amounts of effort have been devoted to inventing novel sensing mechanisms, modifying their designs, improving their performance, and extending their application scopes. However, the reliability and selectivity of most biosensors still have much to be desired, which holds back the development and commercialization of biosensors, especially for on-site and point-of-care (POC) usages. Herein, we introduce an innovative two-phase sensing strategy based on tunable AC electrokinetics and capacitive sensing. By dividing the detection process into a sensitivity-priority step and a selectivity-priority step, the specificity and sensitivity of a biosensor can be significantly improved. A capacitive POC aptasensor is fabricated for the implementation of the 2-phase detection and a quasi-single-cell level detection of limit together with an excellent selectivity is achieved simultaneously. The sensor is capable of handling real-world clinic samples without sophisticated pretreatment. Just after a simple one-step dilution, the developed sensor can detect bacteria no less than 2~3 bacteria/10 µL in raw milk samples within 100 s. Alongside whole bacteria detection, the biosensor can also detect endotoxin, the lipopolysaccharide, in bovine serum samples, with a limit of detection of 10 pg/mL. The biosensor is low-cost and easy to use. This work not only demonstrates a biosensor with significant advantages in sensitivity, selectivity and assay time but also opens up a new horizon for further research of all affinity-based biosensors

Electroanalysis of Small Molecule Therapeutics at Nanostructured Electrode Surfaces

The outbreak of COVID-19 in Wuhan, China in December 2019, resulted in the evolution of a global pandemic which caused thousands of deaths worldwide. As little was known about this new coronavirus, many existing drugs were repurposed with the goal to effectively treat the infection. Two such candidates were dexamethasone (DEX) and N-acetyl-L-cysteine (NAC). Relatively few articles have been published relating to their electrochemical determination, and in this project the use of metal nanoparticles, microparticles and films alongside various carbon nano-onions (CNOs) were explored as chemical modifiers in order to maximize their electrochemical responses. Bare, copper microparticle (CuMPs) and copper film (CuF) modified glassy carbon electrodes were exploited in Chapter 2 to examine the DEX electroreduction response, resulting in sensitivities of 2.00 × 102 μA cm-2 mM-1 and 1.13 × 102 μA cm-2 mM-1 for the CuF and CuMP modified GCEs respectively. Pharmaceutical samples in the form of a cream and a solid-state dose, were analysed with recoveries 77.46 – 87.91 %, with 1.93 – 4.97 % variance. Various types of CNOs were electrochemically characterised of which, oxi-BN-doped-CNOs was selected and combined with gold nanoparticles (AuNPs), resulting in an AuNP/oxi-BN-doped CNO/GCE for NAC quantitation (sensitivity 476 μQ cm-2 mM-1 in acetate buffer). Following design and optimisation, a solid dose form of NAC was quantitatively analysed, resulting in 89 – 105 % ± 6.75 % recovery, thus validating the sensors