ANISOTROPIC POLARIZED LIGHT SCATTER AND MOLECULAR FACTOR COMPUTING IN PHARMACEUTICAL CLEANING VALIDATION AND BIOMEDICAL SPECTROSCOPY

Spectroscopy and other optical methods can often be employed with limited or no sample preparation, making them well suited for in situ and in vivo analysis. This dissertation focuses on the use of a near-infrared spectroscopy (NIRS) and polarized light scatter for two such applications: the assessment of cardiovascular disease, and the validation of cleaning processes for pharmaceutical equipment.There is a need for more effective in vivo techniques for assessing intravascular disorders, such as aortic aneurysms and vulnerable atherosclerotic plaques. These, and other cardiovascular disorders, are often associated with structural remodeling of vascular walls. NIRS has previously been demonstrated as an effective technique for the analysis of intact biological samples. In this research, traditional NIRS is used in the analysis of aortic tissue samples from a murine knockout model that develops abdominal aortic aneurysms (AAAs) following infusion of angiotensin II. Effective application of NIRS in vivo, however, requires a departure from traditional instrumental principles. Toward this end, the groundwork for a fiber optic-based catheter system employing a novel optical encoding technique, termed molecular factor computing (MFC), was developed for differentiating cholesterol, collagen and elastin through intervening red blood cell solutions. In MFC, the transmission spectra of chemical compounds are used to collect measurements directly correlated to the desired sample information.Pharmaceutical cleaning validation is another field that can greatly benefit from novel analytical methods. Conventionally cleaning validation is accomplished through surface residue sampling followed by analysis using a traditional analytical method. Drawbacks to this approach include cost, analysis time, and uncertainties associated with the sampling and extraction methods. This research explores the development of in situ cleaning validation methods to eliminate these issues. The use of light scatter and polarization was investigated for the detection and quantification of surface residues. Although effective, the ability to discriminate between residues was not established with these techniques. With that aim in mind, the differentiation of surface residues using NIRS and MFC was also investigated

\u3csup\u3e26\u3c/sup\u3eAl-Containing Acidic and Basic Sodium Aluminum Phosphate Preparation and Use in Studies of Oral Aluminum Bioavailability from Foods Utilizing \u3csup\u3e26\u3c/sup\u3eAl as an Aluminum Tracer

We synthesized 26Al-containing acidic and basic (alkaline) sodium aluminum phosphates (SALPs) which are FDA-approved leavening and emulsifying agents, respectively, and used them to determine the oral bioavailability of aluminum incorporated in selected foods. We selected applicable methods from published syntheses (patents) and scaled them down (∼3000- and 850-fold) to prepare ∼300–400 mg of each SALP. The 26Al was incorporated at the beginning of the syntheses to maximize 26Al and 27Al equilibration and incorporate the 26Al in the naturally-occurring Al-containing chemical species of the products. Near infrared spectroscopy (NIR) and X-ray powder diffraction (XRD) were used to characterize the two SALP samples and some intermediate samples. Multi-elemental analysis (MEA) was used to determine Na, Al and P content. Commercial products were included for comparison. Satisfactory XRD analyses, near infrared spectra and MEA results confirmed that we synthesized acidic and basic SALP, as well as some of the syntheses intermediates. The 26Al-containing acidic and basic SALPs were incorporated into a biscuit material and a processed cheese, respectively. These were used in oral bioavailability studies conducted in rats in which the 26Al present in blood after its oral absorption was quantified by accelerator mass spectrometry. The results showed oral Al bioavailability from acidic SALP in biscuit was ∼0.02% and from basic SALP in cheese ∼0.05%, lower than our previous determination of Al bioavailability from drinking water, ∼0.3%. Both food and water can appreciably contribute to the Al absorbed from typical human Al intake

Hyperspectral integrated computational imaging

Without Abstract In the past, optics has served mainly to render the world more easily visible to humans. Now, computers are increasingly employed to make sense of the visual world in ways that people cannot. With a new generation of optics, scientists and engineers are recasting visual scenes for interpretation exclusively by computers. To the human eye, these pictures appear distorted at best, or at worst look like visual noise, without discernable meaning. But to computers, such data are worth more than a thousand words. Optimizing complete vision-and-action systems for computers lies at the core of integrated computational imaging. Computers are well-established manipulators of digitized images, and image-processing programs do it routinely on desktop machines. However, what is new is the strategy of modifying image information as it is sensed to make it better suited for the "computer mind" For example, rather than the customary concave and convex disks, optical engineers are fabricating strangely shaped, fundamentally different lenses adapted to the strong points of computers. These optics diverge from the traditional approach in which lenses form something humans recognize as an image. In nature, some beetles navigate by detecting certain colors or the polarization of light in air without forming an image from the data. Scientists have been slow to explore such alternatives, however, because they have modeled optical instruments such as cameras after our own image-rendering eyes. The revolution in integrated computational imaging extends beyond just lenses, however. A new trend in hyperspectral imaging is to speed the visual data processing and reduce data storage requirements by downloading some of the computation to the sensing detector itself. In many cases the detector array can perform both feature extraction (of both physical and spectral features) and encoding of these features. The codes are transmitted by the array to the computer, integrating the computation and imaging (ICI) to reduce the huge data load and speed the processing. Similarly, molecular computing in a multiplex image bandpass spectrometer can accomplish hyperspectral imaging as spatial integrated computational imaging performs feature extractio

Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

BACKGROUND: Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells. METHODS: The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm(2 )for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining. RESULTS: Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously. CONCLUSION: We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of IgY antibodies can lead to new strategies for cancer detection and therapy

Poly(sulfur-random-(1,3-diisopropenylbenzene)) Based Mid-Wavelength Infrared Polarizer: Optical Property Experimental and Theoretical Analysis

Development of polymer based mid-wavelength infrared (MWIR) optics has been limited mainly due to high optical loss of organic polymers used in general optical components. In this study, a MWIR polarization grating based on a sulfuric polymer poly(sulfur-random-(1,3-diisopropenylbenzene)) with a low loss in the MWIR range was fabricated using a simple two-step process: imprint and metal deposition. Fourier-transform infrared (FTIR) spectroscopy measurement showed that this polymeric MWIR polarizer selectively transmitted the polarized IR in transverse magnetic (TM) mode over the transverse electric (TE) mode at normal incidence. The measured extinction ratios (  = The ratio of transmissions in TM and TE) were 208, 176, and 212 at the wavelength of 3, 4, and 5 μm, respectively. The computational simulation and analytical model confirmed that the enhanced TM transmission efficiency and followed a Fabry-Pérot (FP) resonance mode within the created sulfuric polymer film. This polymeric MWIR polarizer demonstrated a great potential for broader applications in IR photonics to realize low-cost and durable optical components

ANISOTROPIC POLARIZED LIGHT SCATTER AND MOLECULAR FACTOR COMPUTING IN PHARMACEUTICAL CLEANING VALIDATION AND BIOMEDICAL SPECTROSCOPY

Spectroscopy and other optical methods can often be employed with limited or no sample preparation, making them well suited for in situ and in vivo analysis. This dissertation focuses on the use of a near-infrared spectroscopy (NIRS) and polarized light scatter for two such applications: the assessment of cardiovascular disease, and the validation of cleaning processes for pharmaceutical equipment. There is a need for more effective in vivo techniques for assessing intravascular disorders, such as aortic aneurysms and vulnerable atherosclerotic plaques. These, and other cardiovascular disorders, are often associated with structural remodeling of vascular walls. NIRS has previously been demonstrated as an effective technique for the analysis of intact biological samples. In this research, traditional NIRS is used in the analysis of aortic tissue samples from a murine knockout model that develops abdominal aortic aneurysms (AAAs) following infusion of angiotensin II. Effective application of NIRS in vivo, however, requires a departure from traditional instrumental principles. Toward this end, the groundwork for a fiber optic-based catheter system employing a novel optical encoding technique, termed molecular factor computing (MFC), was developed for differentiating cholesterol, collagen and elasti

Identification and Characterization of Designer Phencyclidines (PCPs) in Forensic Casework

With the sustained prevalence and introduction of new emerging drugs throughout the world there is a need for continued development and maintenance of platforms that enable rapid identification and characterization of unknown compounds. To complement existing efforts, a collaborative platform between the National Institute of Standards and Technology (NIST) and practicing forensic agencies is being deployed which enables laboratories to leverage techniques and expertise that may not exist at their facilities. Using this approach, unknown compounds are identified and characterized using a suite of analytical tools to obtain (1) a rapid preliminary identification followed by (2) a more complete characterization and confirmation of the preliminary identification. To demonstrate this platform, the characterization of three previously unreported analogs of phencyclidine (PCP) are described. A preliminary identification of the three substances was obtained using direct analysis in real time mass spectrometry (DART-MS) with confirmation by nuclear magnetic resonance (NMR) spectroscopy, gas chromatography mass spectrometry (GC-MS) and gas chromatography flame ionization detection (GC-FID)