Development of methods for the detection of chemical and biological warfare agents

This dissertation sought to find conditions that enabled the characterization of weapons of mass destruction, be that chemical, explosives, or biological, and find unique ion signals for those materials. Chapter 2 examines how to improve the analytical capability of the pulsed glow discharge through an increased understanding of the ionization processes inherent to the technique. Results of a parametric evaluation of ionization processes in the plasma demonstrated that within the glow discharge ion source there are conditions that can be determined which will enhance the signal of the analytical ion. A key innovation was the determination, that in constant power operations, optimal analyte signals could be found 6-8 mm in distance from the cathode and at shorter pulse widths and duty cycles. For the first time, the behavior of argon doubly charged species was characterized in these pulsed plasmas. Whereas the goal of Chapter 2 was to understand the fundamental characteristics of the pulsed glow discharge, Chapters 3 and 4 strive to expand its future possibilities through the coupling of gas chromatography and the pulsed glow discharge ion source to achieve chemical speciation. Chemical speciation can be achieved through structural information from the plateau region and molecular ion information from the afterpeak region and both can be acquired simultaneously. The ability of the pulsed glow discharge to acquire both pieces of information gives the analyst a greater degree of confidence in the identification of the compound; no other technique is capable of providing both pieces of information simultaneously. The purpose of these studies was to determine if the time-gated pulsed glow discharge coupled with gas chromatography mass spectrometry could provide adequate information to detect a chemical warfare agent metabolite or an explosive related compound. We were able to demonstrate that the pulsed glow discharge provides structural information during the plateau for the analytes and we learned that it was important to control the analyte concentration introduced to the plasma so that it does not quench the afterpeak signal. Future directions would focus on lowering the analyte concentration sufficiently. In Chapter 5, we hypothesized that the separation of particles by size would enhance the ability to discriminate between different sources of a Bacillus anthracis surrogate. Size selection was combined with analytical techniques to enhance the capability of identifying biological signatures of bacterial spores. It was found that size separation permitted a more rapid determination by SEM to confirm the presence of spores, but did not enhance the ability of Raman to identify the spores. Ultimately, results from these analyses can be used to build a library to determine an organism\u27s unique biological signature that can be correlated with known growth and processing methods to identify how, when, and where the sample was produced

Vibrational spectroscopy as a powerful tool for stratifying patients using minimal amounts of blood

In the current aging society, more and more people will suffer from age-related diseases such as cardiovascular diseases or diabetes mellitus. To better diagnose and treat these diseases, individual characterisation of the patients unique condition is needed. Vibrational spectroscopy, including Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR), is one of the favourite techniques being developed to enable personalized medicine. Vibrational spectroscopic techniques have the advantages of being non-destructive, rapid, and label-free, can be ultimately performed in high-throughput and provide biochemical fingerprint information on molecular level. Among the samples measured by vibrational spectroscopy, blood is a very popular and important specimen for personalized medicine

On-chip optical sensors

Adding more functionality to chips is an important trend in the advancement of technology. During the past couple of decades, integrated circuit developments have focused on keeping Moore\u27s Law alive More of Moore . Moore\u27s law predicts the doubling of the number of transistors on an integrated circuit every year. My research objectives revolve around More than Moore , where different functionalities are sought to be integrated on chip. Sensing in particular is becoming of paramount importance in a variety of applications. Booming healthcare costs can be reduced with early diagnosis, which requires improved sensitivity and lower cost. To halt global warming, environmental monitoring requires miniature gas sensors that are cheap enough to be deployed at mass scale. First, we explore a novel silicon waveguide platform that is expected to perform well as a sensor in comparison to the conventional 220 nm thick waveguide. 50 and 70 nm shallow silicon waveguides have the advantage of easier lithography than conventional 220 nm thick waveguides due to the large minimum feature size required of 1 µm. 1 µm wide waveguides in these shallow platforms are single mode. A multi-mode interference device is designed in this platform to function as the smallest MMI sensor, giving sensitivity of 427 nm / refractive index unit (RIU) at a length of 4 mm. The silicon photonic MMI sensor is based on detecting refractive index changes. Refractometric techniques such as the MMI sensor require surface functionalization to achieve selectivity or specificity. Spectroscopic methods, usually reserved for material characterization in a research setting, can be adapted for highly specific label-free sensing. Chapter 4 explores the use of a highly doped III-V semiconductor for on chip infrared spectroscopy. Finite element method and finite different time domain were both used to design a plasmonic slot waveguide for gas sensing. On chip lasers and detectors have been designed using InAs. While InAs is still considered more expensive than silicon, the electronics industry expects to start incorporating more materials in standard fabrication processes, including III-V semiconductors for their superior properties including mobility. Thus, experimental realization of this sensor is feasible. A drawback with infrared spectroscopy is that it is difficult to use with biological fluids. Chapter 5 explores the use of Raman spectroscopy as a sensing method. To adapt Raman spectroscopy for sensing, the most important task is to enhance the Raman signal. The way the Raman signal is generated means that the number of photons is generally very low and usually bulk material or concentrated fluids are used as samples. To measure low concentrations of a probe molecule, the probe molecule is placed on a surface enhanced Raman spectroscopy (SERS) substrate. A typical SERS substrate is composed of metal nanostructures for their surface plasmon resonance property, which causes a large amplification in the electric field in particular hot spots. By decorated silicon nanowires with silver nanoparticles, an enhancement factor of 1011 was realized and picomolar concentrations of pyridine were detected using Raman spectroscopy. In conclusion, this thesis provides new concepts and foundations in three directions that are all important for on chip optical sensing. First, silicon photonics is the technology of choice that is nearest to the market and a multi-mode interference sensor based on shallow silicon waveguides was designed. Further work can explore how to cascade such MMIs to increase sensitivity without sacrificing the free spectral range. Second, infrared plasmonics is a promising technology. Before semiconductor plasmonics, on chip devices operated in the visible or near IR and then microwave region of the electromagnetic spectrum. By using highly doped semiconductors, it is possible to bridge the gap and operate with mid-infrared wavelengths. The implications are highlighted by designing a waveguide platform that can be used for next generation on chip infrared spectroscopy. Third, Raman spectroscopy was exploited as a sensing technique by experimental realization of a SERS substrate using equipment-free fabrication methods

Polyelectrolyte based NANO-approaches for Cancer therapy or diagnostics

The work presented here has been aimed at exploring a polymer nanoparticle based approach to cancer diagnostics and therapy. Cancer is the second leading cause of death in the world. Nanoparticles and polymer science have opened up a new world of opportunities for the development of efficient medical diagnostic methods and of selective cancer therapy. The different (sometimes hierarchical and/or multilayer) structures, shapes and compositions of nanoparticles provide good potential for their application in the biomedical field. With the development of nanotechnology, various types of uncoated and coated nanoparticles are being developed for cancer diagnostics and therapy

Optical micro-manipulation in HIV-1 infected cells for improved HIV-1 treatment and diagnosis

Laser application in the field of biological and medical sciences has significantly grown, thereby strengthening the field of Biophotonics. Research conducted in Biophotonics focuses on the concept of using light especially in the visible and near infrared regions of the electromagnetic radiation for the evaluation of living systems. In this thesis new discoveries are presented about low level laser therapy, optical trapping, transmission spectroscopy, luminescence spectroscopy and structured illumination microscopy (SIM), displaying the impact each technique has on HIV infected cells. The results showed that the irradiation of HIV-1 infected TZM-bl cells with low power red laser reduces HIV-1 infection. The outcomes of this study further proved that when irradiation is used in conjunction with efavirenz, an antiretroviral drug, HIV-1 infection could be reduced to undetectable levels in TZM-bl cells. Through the coupling of transmission spectroscopy with optical trapping, and separately, use of luminescence spectroscopy, label free diagnosis of HIV in infected cell samples was achieved. This finding affirms that HIV-1 infection can be detected in a label free manner when using laser based techniques. Furthermore, the photoluminescence spectrometer system was employed to generate a decay curve, which was necessary so as to have some understanding on lifetime of the luminescent signal in infected TZM-bl cells. Finally, in order to confirm that indeed TZM-bl cells were infected, an established super-resolution microscopy system SIM was used to detect HIV-1 infection in TZM-bl cells. Indeed in the infected cells viral molecules p24 and gp41 were detected through SIM, while they were not detected in uninfected cells. In future studies, super resolution microscopy would be coupled to an optical trapping system in order to confirm that each trapped cells is whether infected or uninfected so as to improve HIV diagnosis.College of Science, Engineering and TechnologyPh. D. (Science, Engineering and Technology

ICR ANNUAL REPORT 2019 (Volume 26)[All Pages]

This Annual Report covers from 1 January to 31 December 201

Sensing at nanostructures for agri-food and enviromental applications

With a predicted population increase of 2.3 billion people, by 2050, agricultural productivity must be vastly improved and made sustainable. Globally, agriculture must deliver a 60% increase in food production to cope with the population demand. Moreover, this needs to be achieved against a changing climate, an exploitation of natural resources, and growing water and land scarcities. New digital technologies can optimise production efficiency and ensure food security and safety while also minimising waste within the production systems and the supply chain. To this end, new sensor technologies are being developed for applications in animal health diagnostics and environmental issues related to the global population, such as food & crop protection, pathogen and toxin detection, and environmental remediation. In this thesis, two new nanosensing diagnostic devices are developed and presented; surface enhanced Raman sensing and electrochemical sensing. Surface-enhanced Raman spectroscopy (SERS) substrates were fabricated by templating a flexible thermoplastic polymer against an aluminium drinks can followed by coating with a silver film, to produce a rough nanostructured metallic surface. SERS is used for both qualitative (molecular fingerprint) and quantitative detection of dye molecules and food toxins. In addition, the SERS technique is also applied in combination with nanoelectrochemical square wave voltammetry to detect nano-concentrations of neonicotinoid pesticides. The enhanced sensitivity and minimum sample preparation requirements provide tremendous opportunities for food safety and security sectors. An impedimetric immunosensor device (with a micro SD style pin-out) was also developed for the serological diagnosis of viruses and antibodies associated with bovine respiratory disease and bovine liver fluke. The silicon chip devices consist of six on-chip nanoband electrodes which can be independently modified with a polymer layer for covalent immobilisation of capture and target biomolecules. This electrochemical biosensor technology provides label-free and cost-efficient sensing capability in a compact size, and demonstrates the potential development of immunoassay-based point-of-use devices for on-farm diagnosis or therapeutic monitoring in animal health applications

Infrastructure of Synchrotronic Biosensor Based on Semiconductor Device Fabrication for Tracking, Monitoring, Imaging, Measuring, Diagnosing and Detecting Cancer Cells

Copper Zinc Antimony Sulfide (CZAS) is derived from Copper AntimonySulfide (CAS), a famatinite class of compound. In the current paper, thefirst step for using Copper, Zinc, Antimony and Sulfide as materials inmanufacturing synchrotronic biosensor-namely increasing the sensitivity of biosensor through creating Copper Zinc Antimony Sulfide, CZAS(Cu1.18Zn0.40Sb1.90S7.2) semiconductor and using it instead of CopperTin Sulfide, CTS (Cu2SnS3) for tracking, monitoring, imaging, measuring,diagnosing and detecting cancer cells, is evaluated. Further, optimization oftris(2,2'-bipyridyl)ruthenium(II)(Ru(bpy)32+) concentrations and CopperZinc Antimony Sulfide, CZAS (Cu1.18Zn0.40Sb1.90S7.2) semiconductor as two main and effective materials in the intensity of synchrotron fortracking, monitoring, imaging, measuring, diagnosing and detecting cancercells are considered so that the highest sensitivity obtains. In this regard,various concentrations of two materials were prepared and photon emissionwas investigated in the absence of cancer cells. On the other hand, ccancerdiagnosis requires the analysis of images and attributes as well as collectingmany clinical and mammography variables. In diagnosis of cancer, it isimportant to determine whether a tumor is benign or malignant. The information about cancer risk prediction along with the type of tumor are crucialfor patients and effective medical decision making. An ideal diagnosticsystem could effectively distinguish between benign and malignant cells;however, such a system has not been created yet. In this study, a model isdeveloped to improve the prediction probability of cancer. It is necessary tohave such a prediction model as the survival probability of cancer is highwhen patients are diagnosed at early stages