Detection, Receivers, and Performance of CPFSK and CPCK

Continuous Phase Modulation (CPM) is a power/bandwidth efficient signaling technique for data transmission. In this thesis, two subclasses of this modulation called Continuous Phase Frequency Shift Keying (CPFSK) and Continuous Phase Chirp Keying (CPCK) are considered and their descriptions and properties are discussed in detail and several illustrations are given. Bayesian Maximum Likelihood Ratio Test (MLRT) is designed for detection of CPFSK and CPCK in AWGN channel. Based on this test, an optimum receiver structure, that minimizes the total probability of error, is obtained. Using high- and low-SNR approximations in the Bayesian test, two receivers, whose performances are analytically easy-to-evaluate relative to the optimum receiver, are identified. Next, a Maximum Likelihood Sequence Detection (MLSD) technique for CPFSK and CPCK is considered and a simplified and easy-to-understand structure of the receiver is presented. Finally, a novel Decision Aided Receiver (DAR) for detection of CPFSK and CPCK is presented and closed-form expressions for its Bits Error Rate (BER) performance are derived. Throughout the thesis, performances of the receivers are presented in terms of probability of error as a function of Signal-to-Noise Ratio (SNR), modulation parameters and number of observation intervals of the received waveform. Analytical results wherever possible and, in general, simulation results are presented. An analysis of numerical results is given from the viewpoint of the ability of CPFSK and CPCK to operate over AWGN Channel

Novel Channel Estimation Techniques for Next Generation MIMO-OFDM Wireless Communication Systems: Design and Performance Analysis

During the last decade, major evolutions were introduced for Multiple Input Multiple Output (MIMO) wireless communication systems. To reap the full benefits of MIMO systems, the Base Station (BS) and user equipments require accurate Channel State Information (CSI), which can be acquired using one of the two major approaches for Channel Estimation (CE): pilot-based or blind-based CE. In this thesis, a pilot-based lower complexity channel estimator for Cell-Specific Reference Signals (C-RS) and User Equipment RS (UE-RS) in LTE-A Downlink (DL) system is proposed based on using a hybrid Wiener filter. The proposed system is a sub-optimum scheme that requires 8.8% and 74.5% of the number of computations required by the optimum system and other sub-optimum systems. Moreover, a less computationally complex CE scheme based on Fast Fourier Transform (FFT) is proposed. The presented pilot-based system is validated in end-to-end LTE-A system in terms of throughput, which confirms that the proposed system is suitable for practical implementation. Next, a new blind-based CE technique based on a hybrid OFDM symbol structure for SIMO and MIMO systems is presented. It is shown that the developed system, with enough receive antennas, performs as good as pilot-based system, with similar complexity and better spectral efficiency. Finally, new Resource Grid (RG) configurations that serve the blind-based CE scheme developed for MIMO-OFDM system are presented, with the aim to improve the Mean Squared Error (MSE) performance, while minimizing the number of required receive antennas. Results show that the proposed RG configurations provide superior MSE performance, from the perspective of the blind-based CE scheme under investigation, compared to the LTE-A RG configuration. Throughout the thesis, performances of linear receivers is presented in terms of spectral efficiency as a function of Signal-to-Noise Ratio (SNR), and number of BS antennas. CE techniques are evaluated in terms of MSE as a function of SNR for different channel condi- tions. Analytical results wherever possible and, in general, simulation results are presented

A new class of smart gadolinium contrast agent for tissue pH probing using magnetic resonance imaging

Detecting tissue pH in vivo is extremely vital for medical diagnosis and formulation of treatment decisions. To this end, many investigations have been carried out to develop an accurate and efficient method of in vivo pH measurement. Most of the techniques developed so far suffer from inadequate accuracy, due to poor sensitivity at low concentration of the target or nonspecific interactions within the tissue matrix. To overcome these issues, we describe herein the development of a simple, yet reliable, way to estimate pH with high precision using a Gd(III)-DOTA-silyl-based acid-labile group as a pH-sensitive contrast agent with Magnetic Resonance Imaging (MRI). With this method, a change in T1 weighted image intensity of the newly developed pH-sensitive contrast is directly linked to the proton concentration in the media. As a result, we were able estimate the pH of the target with 95% reliability

Implantable biosensors for real-time strain and pressure monitoring

Implantable biosensors were developed for real-time monitoring of pressure and strain in the human body. The sensors, which are wireless and passive, consisted of a soft magnetic material and a permanent magnet. When exposed to a low frequency AC magnetic field, the soft magnetic material generated secondary magnetic fields that also included the higher-order harmonic modes. Parameters of interest were determined by measuring the changes in the pattern of these higher-order harmonic fields, which was achieved by changing the intensity of a DC magnetic field generated by a permanent magnet. The DC magnetic field, or the biasing field, was altered by changing the separation distance between the soft magnetic material and the permanent magnet. For pressure monitoring, the permanent magnet was placed on the membrane of an airtight chamber. Changes in the ambient pressure deflected the membrane, altering the separation distance between the two magnetic elements and thus the higher-order harmonic fields. Similarly, the soft magnetic material and the permanent magnet were separated by a flexible substrate in the stress/strain sensor. Compressive and tensile forces flexed the substrate, changing the separation distance between the two elements and the higher-order harmonic fields. In the current study, both stress/strain and pressure sensors were fabricated and characterized. Good stability, linearity and repeatability of the sensors were demonstrated. This passive and wireless sensor technology may be useful for long term detection of physical quantities within the human body as a part of treatment assessment, disease diagnosis, or detection of biomedical implant failures

Rapid colorimetric lactoferrin-based sandwich immunoassay on cotton swabs for the detection of foodborne pathogenic bacteria

Cotton swab is the conventional swabbing tool that is usually applied for collecting pathogens from contaminated surfaces, followed by cells lysis and DNA extraction before subjecting to genetic analysis. However, such an approach is time consuming as it involves several steps and requires highly trained personnel to perform the experiment. In this study, we developed a new cotton swab-based detection system that involved integrating bacterial collection, preconcentration and detection on Q-tips. The platform is based on a sandwich assay that can detect different pathogens visually by color changes. Lactoferrin-immobilized cotton is used as a general capturing tool to collect various pathogens from surfaces. The presence of particular bacteria is then detected by immersing the cotton in antibodies attached to different colored nanobeads. The target cell is captured between the lactoferrin and specific antibody-conjugated beads which results in certain color development. The effectiveness of this simply fabricated sensor was demonstrated using Salmonella typhimurium, Salmonella enteritidis, Staphylococcus aureus and Campylobacter jejuni. The intensity of the color on the cotton surfaces increased with increasing the concentration of the pathogenic bacteria. The detection limit was as low as 10 cfu/ml for Salmonella typhimurium and Campylobacter jejuni, 100 cfu/ml for Salmonella enteritidis and 100 cfu/ml for Staphylococcus aureus on chicken meat surface. Moreover, this method showed high selectivity and was further confirmed by loop-mediated isothermal amplification (LAMP). The simplicity and the low cost of this colorimetric sensor renders it applicable to a wide range of other pathogens on different surfaces

Exploring the Utility of ssDNA Aptamers Directed against Snake Venom Toxins as New Therapeutics for Snakebite Envenoming.

Snakebite is a neglected tropical disease that causes considerable death and disability in the tropical world. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Antivenoms are the mainstay therapy for treating the toxic effects of snakebite, but despite saving thousands of lives annually, these therapies are associated with limited cross-snake species efficacy due to venom variation, which ultimately restricts their therapeutic utility to particular geographical regions. In this study, we sought to explore the potential of ssDNA aptamers as toxin-specific inhibitory alternatives to antibodies. As a proof of principle model, we selected snake venom serine protease toxins, which are responsible for contributing to venom-induced coagulopathy following snakebite envenoming, as our target. Using SELEX technology, we selected ssDNA aptamers against recombinantly expressed versions of the fibrinogenolytic SVSPs ancrod from the venom of C. rhodostoma and batroxobin from B. atrox. From the resulting pool of specific ssDNA aptamers directed against each target, we identified candidates that exhibited low nanomolar binding affinities to their targets. Downstream aptamer-linked immobilised sorbent assay, fibrinogenolysis, and coagulation profiling experiments demonstrated that the candidate aptamers were able to recognise native and recombinant SVSP toxins and inhibit the toxin- and venom-induced prolongation of plasma clotting times and the consumption of fibrinogen, with inhibitory potencies highly comparable to commercial polyvalent antivenoms. Our findings demonstrate that rationally selected toxin-specific aptamers can exhibit broad in vitro cross-reactivity against toxin isoforms found in different snake venoms and are capable of inhibiting toxins in pathologically relevant in vitro and ex vivo models of venom activity. These data highlight the potential utility of ssDNA aptamers as novel toxin-inhibiting therapeutics of value for tackling snakebite envenoming

In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate

Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in several clinical settings. However, anticoagulation therapy can be associated with an increased risk of bleeding. There is a lack of specific laboratory tests to determine the level of this drug in blood. This is considered the most important obstacles of using this medication, particularly for patients with trauma, drug toxicity, in urgent need for surgical interventions or uncontrolled bleeding. In this work, we performed Systematic evolution of ligands by exponential enrichment (SELEX) to select specific DNA aptamers against dabigatran etexilate. Following multiple rounds of selection and enrichment with a randomized 60-mer DNA library, specific DNA aptamers for dabigatran were selected. We investigated the affinity and specificity of generated aptamers to the drug showing dissociation constants (Kd) ranging from 46.8–208 nM. The most sensitive aptamer sequence was selected and applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level of detection of the target drug. With further improvement of the assay and optimization, these aptamers would replace conventional antibodies for developing detection assays in the near future.Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in several clinical settings. However, anticoagulation therapy can be associated with an increased risk of bleeding. There is a lack of specific laboratory tests to determine the level of this drug in blood. This is considered the most important obstacles of using this medication, particularly for patients with trauma, drug toxicity, in urgent need for surgical interventions or uncontrolled bleeding. In this work, we performed Systematic evolution of ligands by exponential enrichment (SELEX) to select specific DNA aptamers against dabigatran etexilate. Following multiple rounds of selection and enrichment with a randomized 60-mer DNA library, specific DNA aptamers for dabigatran were selected. We investigated the affinity and specificity of generated aptamers to the drug showing dissociation constants (Kd) ranging from 46.8–208 nM. The most sensitive aptamer sequence was selected and applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level of detection of the target drug. With further improvement of the assay and optimization, these aptamers would replace conventional antibodies for developing detection assays in the near future

Rapid Colorimetric Detection of Pseudomonas aeruginosa in Clinical Isolates Using a Magnetic Nanoparticle Biosensor

A rapid, sensitive, and specific colorimetric biosensor based on the use of magnetic nanoparticles (MNPs) was designed for the detection of Pseudomonas aeruginosa in clinical samples. The biosensing platform was based on the measurement of P. aeruginosa proteolytic activity using a specific protease substrate. At the N-terminus, this substrate was covalently bound to MNPs and was linked to a gold sensor surface via cystine at the C-terminus of the substrates. The golden sensor appears black to naked eyes because of the coverage of the MNPs. However, upon proteolysis, the cleaved peptide–MNP moieties will be attracted by an external magnet, revealing the golden color of the sensor surface, which can be observed by the naked eye. In vitro, the biosensor was able to detect specifically and quantitatively the presence of P. aeruginosa with a detection limit of 102 cfu/mL in less than 1 min. The colorimetric biosensor was used to test its ability to detect in situ P. aeruginosa in clinical isolates from patients. This biochip is anticipated to be useful as a rapid point-of-care device for the diagnosis of P. aeruginosa-related infections

Rapid Colorimetric Detection of Pseudomonas aeruginosa in Clinical Isolates Using a Magnetic Nanoparticle Biosensor

A rapid, sensitive, and specific colorimetric biosensor based on the use of magnetic nanoparticles (MNPs) was designed for the detection of Pseudomonas aeruginosa in clinical samples. The biosensing platform was based on the measurement of P. aeruginosa proteolytic activity using a specific protease substrate. At the N-terminus, this substrate was covalently bound to MNPs and was linked to a gold sensor surface via cystine at the C-terminus of the substrates. The golden sensor appears black to naked eyes because of the coverage of the MNPs. However, upon proteolysis, the cleaved peptide-MNP moieties will be attracted by an external magnet, revealing the golden color of the sensor surface, which can be observed by the naked eye. In vitro, the biosensor was able to detect specifically and quantitatively the presence of P. aeruginosa with a detection limit of 102 cfu/mL in less than 1 min. The colorimetric biosensor was used to test its ability to detect in situ P. aeruginosa in clinical isolates from patients. This biochip is anticipated to be useful as a rapid point-of-care device for the diagnosis of P. aeruginosa-related infections