Dialysis-assisted fiber optic spectroscopy for in situ biomedical sensing

A miniature fiber optic spectrometer enclosed within a semipermeable (dialysis) membrane is proposed for in vivo interstitial sensing applications. The semipermeable membrane acts as a molecular filter, allowing only small molecules to pass through to the sampling volume. This filtering, in principle, should enable continuous in vivo drug sensing, removing the necessity for complex microdialysis systems. We use a biological phantom to examine the reliable detection of a fluorescence signal from small dye molecules in the presence of large fluorophores and scatterers. We find that spectral artefacts arising from scatterers and large fluorophores are substantially suppressed, simplifying the spectral analysis. In addition, the measured sampling rate of 157 s is superior to existing in vivo tissue assaying techniques such as microdialysis, which can take tens of minutes.     

Fiber optic probe for polarized reflectance spectroscopy in vivo: design and performance

We present the design and construction of a fiber optic probe for elastic light scattering spectroscopy in vivo with polarized excitation and polarization sensitive detection. The performance of the fiber probe is evaluated using a suspension of polystyrene spheres placed atop a diffusely scattering substrate, and it demonstrates that the size-dependent characteristics of the scatterers can be extracted in the presence of a highly diffusely scattering background using a linear combination of forward and backward Mie scattering components of the scatterers. Subsequently, Mie theory calculations are performed over a broad range of diagnostically relevant parameters of nuclei-mean diameter, size distribution, and relative refractive index-to understand how the polarized reflectance measurements with the fiber probe can be used to extract morphological information about epithelial tissue. Finally, the feasibility of in vivo measurements with the fiber optic based polarization sensitive light scattering spectroscopy is demonstrated.     

Stabilizer-free poly(lactide-co-glycolide) nanoparticles for multimodal biomedical probes

Apart from the reported PLGA submicro- and microspheres with broad size distribution, we have successfully developed a methodology using nanoprecipitation to prepare different sizes of PLGA nanoparticles with narrow size distributions. The newly developed PLGA nanoparticles could be readily modified with hydrophilic biomaterials on their surface and entrap hydrophobic drugs into their interiors. The encapsulation of FITC inside PLGA nanoparticles displayed a controlled release of drug system. The surfaces of the FITC entrapped PLGA nanoparticles were conjugated with quantum dots to serve as bimodal imaging probes. For nuclear transport, combination of nuclear localization signal (NLS) and PLGA nanoparticles, PLGA nanoparticles could successfully enter into HeLa cells nuclei. From tissue uptake results, PLGA nanoparticles had more uptaken by brain and liver than other tissues. The iron oxide nanoparticles-conjugated PLGA nanoparticle showed high efficiency of relaxivities r2 and could be used as the powerful magnetic resonance imaging (MRI) agents.     

Fiber optic probe cytometer

An optical fiber probe is used to both excite and collect fluorescence from a suspension of cells. The configuration of the probe is such that one or a few cells are sensed at a time, with a convenient cell concentration. With fluorescently labeled antibodies to cellular antigens, the fiber optic cytometer is able to identify the presence of a specific set of cells with high sensitivity.     

Fiber optic near-infrared Raman spectroscopy for clinical noninvasive determination of water content in diseased skin and assessment of cutaneous edema

Currently, measuring Raman spectra of tissues of living patients online and in real time, collecting the spectra in a very short measurement time, and allowing diagnosis immediately after the spectrum is recorded from any body region, are specific advantages that fiber optic near-infrared Raman spectroscopy (NIR RS) might represent for in vivo clinical applications in dermatology. We discuss various methodological aspects and state of the art of fiber optic NIR RS in clinical and experimental dermatology to outline its present advantages and disadvantages for measuring skin in vivo, particularly its water content. Fiber optic NIR Fourier transform (FT) RS has been introduced to dermatological diagnostics to obtain information regarding the molecular composition of the skin up to several hundred micrometers below the skin surface in a relatively fast nondestructive manner. This has been especially important for probing for in vivo assessment of cutaneous (intradermal) edema in patients patch test reactions. Fiber optic NIR FT Raman spectrometers still require further technological developments and optimization, extremely accurate water concentration determination and its intensity calculation in skin tissue, and for clinical applications, a reduction of measurement time and their size. Another promising option could be the possibility of applying mobile and compact fiber optic charge-coupled device (CCD)-based equipment in clinical dermatology.     

Progress towards two-dimensional biomedical imaging with THz spectroscopy

Terahertz spectroscopy represents a frontier in the field of biomedical imaging. It is possible to image complex objects that are opaque to visible and infrared light. In this paper, we have used THz imaging to reveal the structure inside a sunflower seed. We compare images based on time- and frequency-domain representations of the THz scans, and conclude that for this type of specimen the time-domain THz scans provide more detailed information than their frequency-domain counterparts.     

Application of fiber optic luminescent light sources to biomedical studies

Medical Institute, Nizhnii Novgorod, Russia. Translated from Meditsinskaya Tekhnika, No. 2, pp. 13–14, March–April, 1993.     

Fiber order in the opossum's optic tract

Summary The distribution of axons by size in the optic tract of the South American opossum, Didelphis marsupialis was studied. Thin and semi-thin sections were examined, and measurements of axonal diameter were made on electron micrographs taken from various locations across the optic tract of normal opossums. In order to determine the contributions of the different axon diameter classes to the crossed and uncrossed retinofugal pathways, measurements were also made from the tracts of opossums in which one eye had been enucleated 5 weeks previously. Within the opossum's optic tract, the axons are partially segregated by their size: the deepest parts of the tract contain only fine and medium-sized axons, whereas coarse axons are also present superficially. In the middle of the tract, all three size classes are present. At increasingly superficial positions, there is a steady reduction in the proportion of medium-diameter axons, and an increase in the number of the finest axons. Medium and coarse axons contribute to both the crossed and uncrossed pathways, and the uncrossed component is displaced superficially relative to the crossed component. The fine axons in the deeper parts of the tract arise from both retinae, while those in the superficial parts of the tract, near the pial surface, are virtually all crossed. The opossum's optic tract thus displays the segregation of axons by size found in placental mammals, and follows a pattern reminiscent of that found in carnivores. Such a common organizational plan, particularly the similarities between the didelphids and carnivores, is suggestive of an early acquisition of parallel visual pathways in mammalian phylogeny. Since the fiber order in the optic tract of eutherians is a chronological map of axonal arrival during development, these results suggest that a conserved developmental mechanism has led to a common organizational plan.     

Coupling of optical characterization with particle and network synthesis for biomedical applications

Polymeric microspheres containing a magnetic core have been used in cancer therapy for biophysical targeting of antitumor agents and in magnetic resonance imaging as contrasting agents. For the Human Genome Project, deoxyribose nucleic acid (DNA) capillary electrophoresis has become the most widely used analytical technique where a key component is the design of an effective separation medium. The synthesis and optical characterization of polymeric coated superparamagnetic nanoparticles and of (self-assembled) polymer networks by means of a range of physical techniques, including laser light scattering and laser-induced fluorescence detection, are presented. (1) Polymeric microspheres with a superparamagnetic core. A water-in-oil microemulsion approach has been used successfully to synthesize the superparamagnetic core and the polymeric microsphere in one continuous step. The synthesis permits us to control the magnetic nanoparticle size and the thickness of the hydrogel, ranging from 80 to 320 nm. Magnetite concentration in the microspheres, calculated by vibrating-sample magnetometry, was found to be up to 3.3 wt %. The internal structure of the microspheres, as observed by atomic force microscopy, confirmed a core-shell model. (2) Development of new separation media for DNA capillary electrophoresis. Block copolymers in selective solvents can self-assemble to form supramolecular structures in solution. The nanostructures can be characterized in the dilute concentration regime by means of laser light scattering. At semidilute concentrations, the mesh size, the supramolecular structure, and the surface morphology can be investigated by means of small angle x-ray scattering and atomic force microscopy. The structural knowledge and the information on chain dynamics can then be correlated with electrophoresis using laser-induced fluorescence detection to provide a deeper understanding for the development of new separation media.     

Passive electrical isolation of double coil probes for localized spectroscopy and imaging

A circuit is described for the electrical isolation of double coil probes where separate transmitter and receiver coils are both tuned to the same frequency and are coupled by mutual inductance. There are only passive components in the probe, and so no additional control signals are required for switching between transmit and receive conditions. An analysis of the operation of the circuit is included together with details of component selection and setting-up procedures, thus facilitating the implementation of the design for a variety of applications in both imaging and spectroscopy.     

Development of a noncontact diffuse optical spectroscopy probe for measuring tissue optical properties

Optical reflectance probes are often used as tools to obtain optical spectra from superficial tissues and subsequently determine optical and physiological properties associated with early stage cancer. These probes, when placed directly on the tissue, are known to cause significant pressure-dependent changes in local optical properties. To address this, we fit the probe with an optical device that images the illumination and collection fibers onto the tissue surface, eliminating the influence of contact probe pressure on the sampling area. The noncontact probe addition addresses new optical conditions that may affect its performance such as tissue surface contour, and specular reflections by implementing an autofocusing mechanism and cross polarization. Extracted optical properties of tissue simulating phantoms yield errors of 3.46% in reduced scattering and 8.62% in absorbance. Autofocusing has extended the depth of field from 4 mm to throughout the 12 mm range of autofocus travel, while cross polarization has removed the incidence angle dependent specular reflection component from the collected signal.     

生物医学拉曼光谱质控方法研究

目的评价生物医学拉曼光谱设备的关键性能参数,为开展不同厂家产品的一致性比对和建立拉曼光谱类医疗器械的检测规范做准备。方法开发通用的拉曼光谱实验平台,测量化学参考物质,开发光谱分析方法,对实验系统的分辨率、波长校正、信噪比、系统响应等进行分析,并使用几种常见的生物分子进行测试验证。结果根据化学参考物质的拉曼光谱提取了实验系统的光谱分辨率、波长校正、信噪比、系统响应等信息,在测试中可有效地将生物分子的原始拉曼谱还原为可比对的标准拉曼谱。结论本文方法可有效提取和评价拉曼系统的性能参数,这对于拉曼光谱和其他相关光谱医疗器械的质控具有积极意义。