Multifunctional Nanoparticles in Cancer: in vitro Characterization, in vivo Distribution

A novel biocompatible and biodegradable polymer, termed poly(Glycerol malate co-dodecanedioate) (PGMD), was prepared by thermal condensation method and used for fabrication of nanoparticles (NPs). PGMD NPs were prepared using the single oil emulsion technique and loaded with an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The size of the void PGMD NPs, IR820-PGMD NPs and DOX-IR820-PGMD NPs were approximately 90 nm, 110 nm, and 125 nm respectively. An acidic environment (pH=5.0) induced higher DOX and IR820 release compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of DOX-IR820-PGMD NPs was comparable in MES-SA but was higher in Dx5 cells compared to free DOX plus IR820 (pIn vivomouse studies showed that NP formulation significantly improved the plasma half-life of IR820 after tail vein injection. Significant lower IR820 content was observed in kidney in DOX-IR820-PGMD NP treatment as compared to free IR820 treatment in our biodistribution studies (p

Funtional Near Infrared Spectroscopy Study of Language, Joint Attention and Motor Skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Thermoelectric assessment of laser peening induced effects on a metallic biomedical Ti6Al4V

Laser peening has recently emerged as a useful technique to overcome detrimental effects associated to another well-known surface modification processes such as shot peening or grit blasting used in the biomedical field. It is worth to notice that besides the primary residual stress effect, thermally induced effects might also cause subtle surface and subsurface microstructural changes that might influence corrosion resistance. Moreover, since maximum loads use to occur at the surface, they could also play a critical role in the fatigue strength. In this work, plates of Ti-6Al-4V alloy of 7 mm in thickness were modified by laser peening without using a sacrificial outer layer. Irradiation by a Q-switched Nd-YAG laser (9.4 ns pulse length) working in fundamental harmonic at 2.8 J/pulse and with water as confining medium was used. Laser pulses with a 1.5 mm diameter at an equivalent overlapping density (EOD) of 5000 cm-2 were applied. Attempts to analyze the global induced effects after laser peening were addressed by using the contacting and non-contacting thermoelectric power (TEP) techniques. It was demonstrated that the thermoelectric method is entirely insensitive to surface topography while it is uniquely sensitive to subtle variations in thermoelectric properties, which are associated with the different material effects induced by different surface modification treatments. These results indicate that the stress-dependence of the thermoelectric power in metals produces sufficient contrast to detect and quantitatively characterize regions under compressive residual stress based on their thermoelectric power contrast with respect to the surrounding intact material. However, further research is needed to better separate residual stress effects from secondary material effects, especially in the case of low-conductivity engineering materials like titanium alloys.

Development of Swept Source Optical Coherence Tomography and Adaptive Optics Scanning Laser Ophthalmoscopy: Improved Imaging Speed and Handheld Applications

Optical coherence tomography (OCT) is a noninvasive three-dimensional interferometric imaging technique capable of achieving micrometer scale resolution. It is now a standard of care in ophthalmology, where it is used to improve the accuracy of early diagnosis, to better understand the source of pathophysiology, and to monitor disease progression and response to therapy. In particular, retinal imaging has been the most prevalent clinical application of OCT, but researchers and companies alike are developing OCT systems for cardiology, dermatology, dentistry, and many other medical and industrial applications.

Adaptive optics (AO) is a technique used to reduce monochromatic aberrations in optical instruments. It is used in astronomical telescopes, laser communications, high-power lasers, retinal imaging, optical fabrication and microscopy to improve system performance. Scanning laser ophthalmoscopy (SLO) is a noninvasive confocal imaging technique that produces high contrast two-dimensional retinal images. AO is combined with SLO (AOSLO) to compensate for the wavefront distortions caused by the optics of the eye, providing the ability to visualize the living retina with cellular resolution. AOSLO has shown great promise to advance the understanding of the etiology of retinal diseases on a cellular level.

Broadly, we endeavor to enhance the vision outcome of ophthalmic patients through improved diagnostics and personalized therapy. Toward this end, the objective of the work presented herein was the development of advanced techniques for increasing the imaging speed, reducing the form factor, and broadening the versatility of OCT and AOSLO. Despite our focus on applications in ophthalmology, the techniques developed could be applied to other medical and industrial applications. In this dissertation, a technique to quadruple the imaging speed of OCT was developed. This technique was demonstrated by imaging the retinas of healthy human subjects. A handheld, dual depth OCT system was developed. This system enabled sequential imaging of the anterior segment and retina of human eyes. Finally, handheld SLO/OCT systems were developed, culminating in the design of a handheld AOSLO system. This system has the potential to provide cellular level imaging of the human retina, resolving even the most densely packed foveal cones.

Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students

Souza MA, Souza MH, Palheta RC Jr, Cruz PR, Medeiros BA, Rola FH, Magalhaes PJ, Troncon LE, Santos AA. Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students. Adv Physiol Educ 33: 343-348, 2009; doi: 10.1152/advan.90176.2008.-Current medical curricula devote scarce time for practical activities on digestive physiology, despite frequent misconceptions about dyspepsia and dysmotility phenomena. Thus, we designed a hands-on activity followed by a small-group discussion on gut motility. Male awake rats were randomly submitted to insulin, control, or hypertonic protocols. Insulin and control rats were gavage fed with 5% glucose solution, whereas hypertonic-fed rats were gavage fed with 50% glucose solution. Insulin treatment was performed 30 min before a meal. All meals (1.5 ml) contained an equal mass of phenol red dye. After 10, 15, or 20 min of meal gavage, rats were euthanized. Each subset consisted of six to eight rats. Dye recovery in the stomach and proximal, middle, and distal small intestine was measured by spectrophotometry, a safe and reliable method that can be performed by minimally trained students. In a separate group of rats, we used the same protocols except that the test meal contained (99m)Tc as a marker. Compared with control, the hypertonic meal delayed gastric emptying and gastrointestinal transit, whereas insulinic hypoglycemia accelerated them. The session helped engage our undergraduate students in observing and analyzing gut motor behavior. In conclusion, the fractional dye retention test can be used as a teaching tool to strengthen the understanding of basic physiopathological features of gastrointestinal motility.

Stimuli-responsive magnetic particles for biomedical applications

In recent years, magnetic nanoparticles have been studied due to their potential applications as magnetic carriers in biomedical area. These materials have been increasingly exploited as efficient delivery vectors, leading to opportunities of use as magnetic resonance imaging (MRI) agents, mediators of hyperthermia cancer treatment and in targeted therapies. Much attention has been also focused on ""smart"" polymers, which are able to respond to environmental changes, such as changes in the temperature and pH. In this context, this article reviews the state-of-the art in stimuli-responsive magnetic systems for biomedical applications. The paper describes different types of stimuli-sensitive systems, mainly temperature- and pH sensitive polymers, the combination of this characteristic with magnetic properties and, finally, it gives an account of their preparation methods. The article also discusses the main in vivo biomedical applications of such materials. A survey of the recent literature on various stimuli-responsive magnetic gels in biomedical applications is also included. (C) 2010 Elsevier B.V. All rights reserved.

Noise reduction in biomedical speech signal processing based on time and frequency Kalman filtering combined with spectral subtraction

The goal of this paper is to study and propose a new technique for noise reduction used during the reconstruction of speech signals, particularly for biomedical applications. The proposed method is based on Kalman filtering in the time domain combined with spectral subtraction. Comparison with discrete Kalman filter in the frequency domain shows better performance of the proposed technique. The performance is evaluated by using the segmental signal-to-noise ratio and the Itakura-Saito`s distance. Results have shown that Kalman`s filter in time combined with spectral subtraction is more robust and efficient, improving the Itakura-Saito`s distance by up to four times. (C) 2007 Elsevier Ltd. All rights reserved.

Methods of Fourier optics in digital holographic microscopy

In this paper, processing methods of Fourier optics implemented in a digital holographic microscopy system are presented. The proposed methodology is based on the possibility of the digital holography in carrying out the whole reconstruction of the recorded wave front and consequently, the determination of the phase and intensity distribution in any arbitrary plane located between the object and the recording plane. In this way, in digital holographic microscopy the field produced by the objective lens can be reconstructed along its propagation, allowing the reconstruction of the back focal plane of the lens, so that the complex amplitudes of the Fraunhofer diffraction, or equivalently the Fourier transform, of the light distribution across the object can be known. The manipulation of Fourier transform plane makes possible the design of digital methods of optical processing and image analysis. The proposed method has a great practical utility and represents a powerful tool in image analysis and data processing. The theoretical aspects of the method are presented, and its validity has been demonstrated using computer generated holograms and images simulations of microscopic objects. (c) 2007 Elsevier B.V. All rights reserved.

MEMS-based incandescent microlamps for integrated optics applications

In this work we present the fabrication and operation of incandescent microlamps for integrated optics applications. This microlamp emits white and infrared light from a chromium resistor embedded in a free-standing silicon oxynitride (SiO(x)N(y)) cantilever that can be coupled to an optical waveguide. In fact, the chromium resistor is sandwiched between layers of SiO(x)N(y) that isolate it from the atmosphere, while electric current heats the resistor to incandescent temperatures. The same SiO(x)N(y) material used in the microlamp fabrication is also used to produce the optical waveguides to allow a monolithic integration of light source and optical circuit. Front-side bulk micromachining of the silicon substrate in potassium hydroxide (KOH) solution is used to fabricate the cantilevers that thermally isolate the resistors from the substrate, thus reducing the heat transfer and the current required to light the lamp.

Experimental study of the quantum driven pendulum and its classical analog in atom optics

We present experimental results for the dynamics of cold atoms in a far detuned amplitude-modulated optical standing wave. Phase-space resonances constitute distinct peaks in the atomic momentum distribution containing up to 65% of all atoms resulting from a mixed quantum chaotic phase space. We characterize the atomic behavior in classical and quantum regimes and we present the applicable quantum and classical theory, which we have developed and refined. We show experimental proof that the size and the position of the resonances in phase space can be controlled by varying several parameters, such as the modulation frequency, the scaled well depth, the modulation amplitude, and the scaled Planck’s constant of the system. We have found a surprising stability against amplitude noise. We present methods to accurately control the momentum of an ensemble of atoms using these phase-space resonances which could be used for efficient phase-space state preparation.

A scheme for efficient quantum computation wtih linear optics

Quantum computers promise to increase greatly the efficiency of solving problems such as factoring large integers, combinatorial optimization and quantum physics simulation. One of the greatest challenges now is to implement the basic quantum-computational elements in a physical system and to demonstrate that they can be reliably and scalably controlled. One of the earliest proposals for quantum computation is based on implementing a quantum bit with two optical modes containing one photon. The proposal is appealing because of the ease with which photon interference can be observed. Until now, it suffered from the requirement for non-linear couplings between optical modes containing few photons. Here we show that efficient quantum computation is possible using only beam splitters, phase shifters, single photon sources and photo-detectors. Our methods exploit feedback from photo-detectors and are robust against errors from photon loss and detector inefficiency. The basic elements are accessible to experimental investigation with current technology.

Effect of multiple transverse modes in self-mixing sensors based on vertical-cavity surface-emitting lasers

We investigate the effect of coexisting transverse modes on the operation of self-mixing sensors based on vertical-cavity surface-emitting lasers (VCSELs). The effect of multiple transverse modes on the measurement of displacement and distance were examined by simulation and in laboratory experiment. The simulation model shows that the periodic change in the shape and magnitude of the self-mixing signal with modulation current can be properly explained by the different frequency-modulation coefficients of the respective transverse modes in VCSELs. The simulation results are in excellent agreement with measurements performed on single-mode and multimode VCSELs and on self-mixing sensors based on these VCSELs.

Molecular cocrystals of carboxylic acids. XXVII - An investigation into the use of triphenylphosphine oxide cocrystals for non-linear optics: the crystal structure of the adduct of triphenylphosphine oxide with N-methylpyrrole-2-carboxylic acid

Four adducts of triphenylphosphine oxide with aromatic carboxylic acids have been synthesized and tested for second-order non-linear optical properties. These were with N-methylpyrrole-2-carboxylic acid (I), indole-2-carboxylic acid (2), 3-dimethylaminobenzoic acid (3), and thiophen-2-carboxylic acid (4). Compound (1) produced clear, colourless crystals (space group P2(1)2(1)2(1) With a 9.892(1), b 14.033(1), c 15.305(1) Angstrom, Z 4) which allowed the structure to be determined by X-ray diffraction.