Reinhard F. Bruch

Fourier transform infrared evanescent wave (FTIR-FEW) spectroscopy of tissue

A new Fourier transform infrared fiberoptic evanescent wave (FTIR-FEW) spectroscopy method has been developed for tissue diagnostics in the middle infrared (MIR) wavelength range (3 to 20 micrometers). Specific novel fiberoptical chemical and biological sensors have been studied and used for spectroscopic diagnostic purposes. These nontoxic and nonhygroscopic fiber sensors are characterized by (1) low optical losses (0.05 to 0.2 dB/m at about 10 micrometer) and (2) high flexibility. Our new fiber optical devices can be utilized with standard commercially available Fourier transform spectrometers including attenuated total reflection (ATR) techniques. They are in particular ideally suited for noninvasive, fast, direct, sensitive investigations of in vivo and ex vivo medical diagnostics applications. Here we present data on IR spectra of skin tissue in vivo for various cases of melanoma and nevus in the range of 1480 - 1800 cm-1. The interpretation of the spectra of healthy and different stages of tumor and cancer skin tissue clearly indicates that this technique can be used for precancer and cancer diagnostics. This technique can be designed for real-time and on-line computer modeling and analysis of tissue changes.

Infrared fiber optic evanescent wave spectroscopy: applications in biology and medicine

A new powerful and highly sensitive technique for non-invasive biomedical diagnostics in vivo has been developed using Infrared Fiberoptic Evanescent Wave Fourier Transform Spectroscopy (FEW-FTIR). This compact and portable method allows to detect functional chemical groups and bonds via vibrational spectroscopy directly from surfaces including living tissue. Such differences and similarities in molecular structure of tissue and materials can be evaluated online. Operating in the attenuated total reflection (ATR) regime in the middle-infrared (MIR) range, the FEW-FTIR technique provides direct contact between the fiber probe and tissue for non-destructive, non-invasive, fast and remote (few meters) diagnostics and quality control of materials. This method utilizes highly flexible and extremely low loss unclad fibers, for example silver halide fibers. Applications of this method include investigations of normal skin, precancerous and cancerous conditions, monitoring of the process of aging, allergic reactions and radiation damage to the skin. This setup is suitable as well for the detection of the influence of environmental factors (sun, water, pollution, and weather) on skin surfaces. The FEW-FTIR technique is very promising also for fast histological examinations in vitro. In this review, we present recent investigations of skin, breast, lung, stomach, kidney tissues in vivo and ex vivo (during surgery) to define the areas of tumor localization. The main advantages of the FEW-FTIR technique for biomedical, clinical, and environmental applications are discussed.

Investigations of thermotropic phase behavior of newly developed synthetic PEGylated lipids using Raman spectro‐microscopy

In this article, a temperature-controlled Raman spectro-microscopic technique has been utilized to detect and analyze the phase behaviors of two newly developed synthetic PEGylated lipids trademarked as QuSomes, which spontaneously form liposomes upon hydration in contrast to conventional lipids. The amphiphiles considered in this study differ in their hydrophobic hydrocarbon chain length and contain different units of polyethylene glycol (PEG) hydrophilic headgroups. Raman spectra of these new artificial lipids have been recorded in the spectral range of 500-3100 cm(-1) by using a Raman microscope system in conjunction with a temperature-controlled sample holder. The gel to liquid phase transitions of the sample lipids composed of pure 1,2-dimyristoyl-rac-glycerol-3-dodecaethylene glycol (GDM-12) and 1,2-distearoyl-rac-glycerol-3-triicosaethylene glycol (GDS-23) have been revealed by plotting peak intensity ratios in the C-H stretching region as a function of temperature. From this study, we have found that the main phase transitions occur at a temperature of approximately 5.2 and 21.2 degrees C for pure GDM-12 and GDS-23, respectively. Furthermore, the lipid GDS-23 also shows a postphase transition temperature at 33.6 degrees C. To verify our results, differential scanning calorimetry (DSC) experiments have been conducted and the results are found to be in an excellent agreement with Raman scattering data. This important information may find application in various studies including the development of lipid-based novel substances and drug delivery systems.

FEW-FTIR spectroscopy applications and computer data processing for noninvasive skin tissue diagnostics in vivo

New applications for the Fiberoptic Evanescent Wave Fourier Transform Infrared (FEW-FTIR) method have been developed for the diagnostics of skin surfaces. Our technique allows for the detection of functional groups in the molecular structure of skin tissue noninvasively and in vivo. The FEW-FTIR spectroscopic method is direct, nondestructive, and fast. Our optical fibers for the middle infrared (MIR) range are nontoxic, nonhygroscopic, flexible, and characterized by extremely low losses. This combination of traditional FTIR spectroscopy and advanced fiber technology has enabled us to noninvasively investigate normal and cancerous skin tissue in vivo in the range of 900 to 4000 cm-1. We have developed a special software package of programs with database for the treatment of spectral data that utilizes wavelet analysis, principle component analysis (PCA), image processing, artificial neural fuzzy logic, and data fusion. These programs provide us with the ability to make base line corrections, normalize spectra, and determine peak positions from second order derivative spectra. In this study, we investigated normal, precancerous, and cancerous skin tissue in the range 1480 to 1800 cm-1 using these programs. The results of our surface analysis of skin tissue are discussed in terms of spectral parameters, DNA band assignments, and molecular structural similarities and differences.

Near-infrared spectroscopy of newly developed PEGylated lipids

Near-infrared (NIR) spectroscopy has been used to analyze a suite of synthesized PEGylated lipids (1-3) trademarked as QuSomes. The three amphiphiles used in this study, differ in their hydrophobic chain length and contain various units of polyethylene glycol (PEG) head groups. Whilst the spectra of QuSomes show a common pattern, differences in the spectra are observed which enable the lipids to be distinguished. NIR absorption spectra of these new artificial lipids have been recorded in the spectral range of 4800-9000 cm(-1) (approximately 2100-1100 nm) by using a new miniaturized spectrometer based on micro-optical-electro-mechanical systems (MOEMS) technology. Three NIR spectral regions are identified, (a) the high wavenumber region between 6500 and 9000 cm(-1) attributed to the first overtone of the hydroxyl stretching and second overtone of the C-H stretching mode; (b) the 5350-5900 cm(-1) region attributed to first overtone of the C-H stretching mode; and (c) the 4800-5300 cm(-1) region attributed to the combination O-H stretching and second overtone of the C=O stretching mode. For each of these regions, the lipids show distinctive spectra which allow their identification and characterization. NIR spectroscopy is a less used technique which does have great potential for the study of lipids, particularly to examine the behaviour of nanovesicles (liposomes) formed from lipids in aqueous suspensions. The study of such lipids is important since they are used as membrane models and prominent candidate for substance and drug delivery systems.

A novel dual-detector micro-spectrometer

Infrared analysis is a well-established tool for measuring composition and purity of various materials in industrial-, medical- and environmental applications. Traditional spectrometers, for example Fourier Transform Infrared (FTIR) Instruments are mainly designed for laboratory use and are generally, too large, heavy, costly and delicate to handle for remote applications. With important advances in the miniaturization, ruggedness and cost efficiency we have designed and created a new type of a micromirror spectrometer that can operate in harsh temperature and vibrating environments This device is ideally suited for environmental monitoring, chemical and biological applications as well as detection of biological warfare agents and sensing in important security locations In order to realize such compact, portable and field-deployable spectrometers we have applied MOEMS technology. Thus our novel dual detector micro mirror system is composed of a scanning micro mirror combined with a diffraction grating and other essential optical components in order to miniaturize the basic modular set-up. Especially it periodically disperses polychromatic radiation into its spectral components, which are measured by a combination of a visible (VIS) and near infrared (NIR) single element detector. By means of integrated preamplifiers high-precise measurements over a wide dynamic wavelength range are possible. In addition the spectrometer, including the radiation source, detectors and electronics can be coupled to a minimum-volume liquid or gas-flow cell. Furthermore a SMA connector as a fiber optical input allows easy attachment of fiber based probes. By utilizing rapid prototyping techniques, where all components are directly integrated, the micro mirror spectrometer is manufactured for the 700-1700 nm spectral range. In this work the advanced optical design and integration of the electronic interface will be reviewed. Furthermore we will demonstrate the performance of the system and present characteristic measurement results. Finally advanced packaging issues and test results of the device will be discussed.

Biocompatibility of polymer surfaces interacting with living tissue

The method of vibrational spectroscopy has been applied as a new tool for the biodiagnostics of polymer implants and tissue surfaces. In this study the spectral analysis of polymer implants has been accomplished by means of Fourier transform infrared spectroscopy (FTIR) to elucidate the long-term biocompatibility and quality control of biomedical materials. Surface analysis allows the determination of the specific molecular composition and structures most appropriate for long-term compatibility in humans. Important information associated with the bioinertness or bioactivity of implants has been obtained from the spectral features of the polymer material used, including the level of polymerization. Passivated surfaces of implants have also been obtained and analyzed by means of FTIR.

Correlation, relativistic and radiative effects for the energy levels of 1s22s22p5nl, 1s22s2p5nl (n = 3-6, l=s, p, d, f) configurations of Ne-like ions with Z=20-60

Calculations of energy levels of 1s22s22p5nl, 1s22s2p6nl (n = 3?6, l = s, p, d, f) configurations of Ne-like ions with Z = 20-60 have been carried out with use of an MZ program. The energy matrix in this method (1/Z method or Z?expansion) is represented in the form of a Z-expansion, where Z is the nuclear charge. Relativistic effects are taken into account in the framework of the Breit operator. The contributions of radiative and high order relativistic effects are also considered. The results of the calculations are compared with theoretical and experimental data.

Numerous applications of fiber optic evanescent wave Fourier transform infrared (FEW-FTIR) spectroscopy for subsurface structural analysis

A new infrared (IR) interferometric method has been developed in conjunction with low-loss, flexible optical fibers, sensors, and probes. This combination of fiber optical sensors and Fourier Transform (FT) spectrometers can be applied to many fields, including (1) noninvasive medical diagnostics of cancer and other different diseases in vivo, (2) minimally invasive bulk diagnostics of tissue, (3) remote monitoring of tissue, chemical processes, and environment, (4) surface analysis of polymers and other materials, (5) characterization of the quality of food, pharmacological products, cosmetics, paper, and other wood-related products, as well as (6) agricultural, forensic, geological, mining, and archeological field measurements. In particular, our nondestructive, fast, compact, portable, remote and highly sensitive diagnostics tools are very promising for subsurface analysis at the molecular level without sample preparation. For example, this technique is ideal for different types of soft porous foams, rough polymers, and rock surfaces. Such surfaces, as well as living tissue, are very difficult to investigate by traditional FTIR methods. We present here FEW-FTIR spectra of polymers, banana and grapefruit peels, and living tissues detected directly at surfaces. In addition, results on the vibrational spectral analysis of normal and pathological skin tissue in the region of 850 - 4000 cm-1 are discussed.

Investigation of normal human skin tissue and acupuncture points of human skin tissue using fiberoptical FTIR spectroscopy

An innovative spectroscopic diagnostic method has been developed for investigation of different regions of normal human skin tissue. This new method is a combination of Fourier transform IR fiberoptic evanescent wave (FTIR-FEW) spectroscopy and fiber optic techniques for the middle IR (MIR) wavelength range. The fiber optical sensors we have used are characterized by low optical losses and high flexibility for remote analysis. Our fiber optical accessories and method allows for direct interaction of the skin tissue with the fiber probe and can be utilized with a diversity of standard commercial Fourier transform spectrometers. The FTIR-FEW technique, using nontoxic unclad fibers in the attenuated total reflection regime, is suitable for noninvasive, fast, sensitive investigations of normal skin in vivo for various medical diagnostics applications including studies of acupuncture points. Here we present the first data on IR spectra of skin tissue in vivo for normal skin and several acupuncture points in the range of 1300 to 1800 cm-1 and 2600 to 4000 cm-1.