Synthetic drugs such as piperazines are among the most commonly abused drugs and are typically consumed by younger populations. Because of their popularity, developing optimized analytical strategies designed to improve detection and interpretation of synthetic piperazines is of interest to the forensic community. To improve the likelihood that a substance of interest is detected, careful evaluation into the mass spectrometry signal is required. However, with all analytical pursuits, there is a limit at which the substance cannot be detected with certainty; thus a threshold is commonly referred to as the limit of detection (LOD). Formally, the LOD is the minimum amount of analyte (concentration, mass, number of molecules, etc.) that can be detected at a known confidence level. The purpose of this research was to use common analytical methods to calculate the LOD and verify the results with previous work at the Boston University forensic toxicology laboratory. Data from the Liquid Chromatography-tandem Mass Spectrometer (LC-MS/MS) was previously generated and consisted of signal intensity information in the form of peak height and peak area, from titrations of eight synthetic piperazines that included: Benzylpiperazine (BZP), 1-(3-chlorophenyl)-piperazine (mCPP), 3-trifluoromethylphenylpiperazine monohydrochloride (TFMPP), methylbenzylpiperazine (MBZP), 1-(4-fluorobenzyl)-piperazine (FBZP), 2,3-dichlorophenylpiperazine (DCPP), para-fluorophenylpiperazine (pFPP) and para-methoxyphenylpiperazine (MeOPP). Generally, the LOD is determined by first evaluating the signal in the absence of analyte and determining the probability that signal, , crosses the signal threshold, . The signal threshold is based upon the false detection rate the laboratory can withstand for a given interpretation scheme. In instances where very small levels of false detections can be tolerated, a large is chosen. In other circumstances, where noise detection can adequately be interpreted, a low is chosen. In chromatography and radiography the typical one sided =0.003. The number of molecules for each analyte at each concentration (20 ng/mL, 50 ng/mL, 200 ng/mL, 500 ng/mL, 1000 ng/mL and 2000 ng/mL) was determined and used throughout this work. Peak area signals and ratios versus number of molecules for each analyte were used to, first, visually inspect the linearity of signal to analyte level. It was determined that using internal standards improved linearity, as expected; however, the data suggested that absolute signal intensity was sufficient to compute the LOD for these compounds. Generally accepted methods of calculating LOD were not used for this research as the signal from the blank was not detected most likely due to the sensitivity of the instrument used. This study used an extrapolation of the data and propagation of errors method to calculate the LOD as the signal from the blank was not needed. For all eight analytes, the LOD calculated was similar to the lowest concentration (20 ng/mL) used when validating this method. This research needs to be expanded on to include more concentration points and see the plateau effect at higher concentrations. This will provide information to analytical chemists when a blank signal is not available about how the LOD can be calculated with high confidence.

>Magister Scientiae - MSc / The tuberculosis (TB) disease to this day remains one of the world’s prominent killerdiseases. Pyrazinamide (PZA) is one of the most commonly prescribed anti- tuberculosis (anti-TB) drugs due to its ability to significantly shorten the TB treatment period from the former nine months to the current six months duration. However, excess PZA in the body causes hepatotoxicity and damages the liver. This hepatotoxicity, together with the resistance of the bacteria to treatment drugs, poor medication and inappropriate dosing, greatly contribute to the high incidents of TB deaths and diseases that are due to side effects (such as liver damage). This brings about the calls for alternative methods for ensuring reliable dosing of the drug, which will be specific from person to person due to inter-individual differences in drug metabolism. A novel biosensor system for monitoring the metabolism of PZA was prepared with a Ni-PPI-PPy star copolymer and cytochrome P450 2E1 (CYP2E1) deposited onto a platinum electrode. The nanobiosensor system exhibited enhanced electro-activity that is attributed to the catalytic effect of the incorporated star copolymer. The biosensor had a sensitivity of 0.142 µA.nM-1, and a dynamic linear range (DLR) of 0.01 nM-0.12 nM (1.231 – 7.386 ng/L PZA). The limit of detection of the biosensor was found to be 0.00114 nM (0.14 ng/L) PZA. From the HPLC peakconcentration (Cmax) of PZA determined 2 h after drug intake is 2.79 – 3.22 ng.L-1,which is very detectable with the nanobiosensor as it falls within the dynamic linear range.

>Magister Scientiae - MSc / The motivation to determine H2O2 lies in the fact that this chemical species plays a crucial role in diverse fields of practise such as cosmetic, food, diagnostic, pharmaceutical, clinical and environmental protection industries. Several methods such as chromatography, colorimetry, titrimetry and spectrophotometry have been developed for its detection. However, these methods are known to manifest underlying disadvantages such as high cost, time consuming, instability and complicated immobilization procedures. In this present study an enzyme-less electrochemical sensor based on Ag-Fe2O3/POM/RGO nanocomposite (POM stands for polyoxometalate and RGO stands for reduced graphene oxide) was successfully synthesised via a hydrothermal method and a photochemical reduction method for the detection of hydrogen peroxide (H2O2).

The melamine incident 2008 was a global food crisis and drew attentions to other potential food safety risks. Although there are regulations and standards for food safety, but one common problem in food risk management is that it lacks on hazard indicators - indicators in ranking of food risk and control. The three algorithms developed in this article were: 1. A distribution fitting algorithm proposed to estimate population parameters for left-censored melamine data under log-normal assumption. 2. A risk index algorithm proposed to screen out food product categories with higher concentration without considering measurement uncertainty. 3. A misjudgment probability algorithm proposed to calculate the probability that food categories containing melamine more than legal limit but classified satisfactory under consideration of measurement uncertainty. The test results on melamine collected from the website of the Centre for Food Safety of Hong Kong are empirically analyzed by the proposed algorithms. The risk index (RI) and the consumer¡¦s risk (CR) of multiple food categories are discussed and compared in details. Based on risk index (RI) and consumer¡¦s risk (CR), we build a risk assessment process to help assess melamine risk and make sample strategy in surveillance programme. The proposed risk assessment process can be applied to other chemical contaminant problems such as plasticizer (phthalate esters) and ractopamine (paylean), etc.

Surface plasmon resonance (SPR) sensors are advantageous to other techniques of sensing chemical binding, offering quantitative, real-time, label-free results. Previous work has demonstrated the effectiveness of using dual-mode SPR sensors to differentiate between surface and background effects, making the sensors more robust to dynamic environments. This work demonstrates a technique that improves upon a previously optimized planar film dual-mode SPR sensor’s LOD by introducing a periodic array of subwavelength nano-gaps throughout the plasmon supporting material. First, general figures of merit for a sensor having an arbitrary number of modes are studied. Next, the mode effective index dispersion and magnetic field profiles of the two strongly bound modes found using a gap width of 20nm are analyzed. Qualitative analysis of the results demonstrates how such a design can enable better LODs in terms of each figure of merit. By optimizing a nano-gap enhanced sensor containing 20nm gaps, it is quantitatively demonstrated that the resulting modes improve upon almost every figure of merit, especially with respect to the orthogonality and magnitude of the sensitivity vectors, resulting in LODs approximately a factor of five less than the optimal planar design.

Surface plasmons are bound TM polarized electromagnetic waves that propagate along the interface of two materials with real dielectric constants of opposite signs. Surface plasmon resonance (SPR) sensors make use of the surface plasmon waves to detect refractive index changes occurring near this interface. For sensing purposes, this interface typically consists of a metal layer, usually gold or silver, and a liquid dielectric. SPR sensors usually measure the shift in resonance wavelength or resonance angle due to index changes adjacent to the metal layer. However this restricts the limit of detection (LOD), as the regions of low slope (intensity vs. wavelength or angle) in the SPR curve contain little information about the resonance. This work presents the technique of tunable laser interrogation of SPR sensors. A semiconductor laser with a typical lasing wavelength of 650nm was used. A 45nm gold layer sputtered on a BK7 glass substrate served as the sensor. The laser wavelength is tuned to always operate in the region of highest slope by using a custom-designed LabVIEW program. It is shown that the sensitivity is maximized and LOD is minimized by operating around the region of high slope on the SPR curve.

Sir Alec Jeffreys was the first to describe human identification with deoxyribonucleic acid (DNA) in his seminal work in 1985 (1); the result was the birth of forensic DNA analysis. Since then, DNA has become the primary substance used to conduct human identification testing. Forensic DNA analysis has evolved since the work of Jeffreys and now incorporates the analysis of 15 to 24 STR (short tandem repeat) locations, or loci (2-4). The simultaneous amplification and subsequent electrophoresis of tens of STR polymorphisms results in analysis that are highly discriminating. DNA target masses of 0.5 to 2 nanograms (ng) are sufficient to obtain a full STR profile (4); however, pertinent information can still be obtained if low copy numbers of DNA are collected from the crime scene or evidentiary material (4-9). Despite the sensitivity of polymerase chain reaction (PCR) - capillary electrophoresis (CE) based technology, low copy DNA signal can be difficult to interpret due to the preponderance of low signal-to-noise ratios. Due to the complicated nature of low template signal, optimization of the DNA laboratory process such that high-fidelity signal is regularly produced is necessary; studies designed to effectively hone in on optimized laboratory conditions are presented herein. The STR regions of a set of samples containing 0.0078 ng of DNA were amplified for 29 cycles; the amplified fragments were separated using two types of CE platforms: an ABI 3130 Genetic Analyzer and an ABI 3500 Genetic Analyzer. The result is a genetic trace, or electropherogram (EPG), comprised of three signal components that include noise, artifact, and allele. The EPGs were analyzed using two peak detection software programs. In addition, a tool, termed Simulating Evidentiary Electropherograms (SEEIt) (10, 11), was utilized to simulate EPG signal obtained when one copy of DNA is processed through the forensic pipeline. SEEIt was parameterized to simulate data corresponding to two laboratory scenarios: the amplification of a single copy of DNA injected on an ABI 3130 Genetic Analyzer and on an ABI 3500 Genetic Analyzer. In total, 20,000 allele peaks and 20,000 noise peaks were generated for each CE platform. Comparison of simulated and experimental data was used to elucidate features that are difficult to ascertain by experimental work alone. The data demonstrate that experimental signal obtained with the ABI 3500 platform results in signal that is, on average, a factor of four larger than signal obtained from the ABI 3130 platform. When a histogram of the signal is plotted, a multi modal distribution is observed. The first mode is hypothesized to be the result of noise, while the second, third, etc. modes are the signal obtained when one, two, etc. target DNA molecules are amplified. By evaluating the data in this way, full signal resolution between noise and allelic signal is visualized. Therefore, this methodology may be used to: 1) optimize post-PCR laboratory conditions to obtain excellent resolution between noise and allelic signal; and 2) determine an analytical threshold (AT) that results in few false detections and few cases of allelic dropout. A χ2 test for independence of the experimental signal in noise positions and the experimental signal within allele positions < 12 relative fluorescence units (RFU), i.e. signal in the noise regime, indicate the populations are not independent when sufficient signal-to-noise resolution is obtained. Once sufficient resolution is achieved, optimized ATs may be acquired by evaluating and minimizing the false negative and false positive detection rates. Here, a false negative is defined as the non-detection of an allele and a false positive is defined as the detection of noise. An AT of 15 RFU was found to be the optimal AT for samples injected on the ABI 3130 for at least 10 seconds (sec) as 99.42% of noise peaks did not exceed this critical value while allelic dropout was kept to a minimum, 36.97%, at this AT. Similarily, in examining signal obtained from the ABI 3500, 99.41% and 99.0% of noise fell under an AT of 50 RFU for data analyzed with GeneMapper ID-X (GM) and OSIRIS (OS), respectively. Allelic dropout was 36.34% and 36.55% for GM and OS, respectively, at this AT.

In this paper, metal-enhanced fluorescence (MEF) technique is used to lower the detection limit of carcinoembryonic antigen (CEA) which is able to be utilized in forecasting the risk of having certain kinds of cancers, especially colon and rectal cancer. By incubating silver nanocubes (Ag NCs) on the surface of the chips, the detection limit goes down to below 1ng/mL of CEA. Also, when combining MEF with surface acoustic wave (SAW) devices, the incubation time between antigen and antibody will decrease significantly with the fluorescence signal keeping similar or higher level.

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