This work presents the design and implementation of an endoscopic probe for point-of-care diagnosis of bladder cancer, with an outer diameter of 4.5 mm that allows for in-vivo usage. This triple-modality device can deliver volumetric OCT images, optoacoustic tomograms, and single point Raman spectroscopy that target complementary biomarkers. The probe features a piezo-based fiber scanner, which delivers the illumination or excitation light for all modalities, with a maximum Field of View of 1.6 mm. The same path is used for light collection for OCT imaging. A separate fiber is used for detection of the Raman signals, while two additional fibers with microcavity tips sense the ultrasonic waves for optoacoustic tomography. A hyperchromatic micro-optical objective provides a working distance optimized for each modality. The probe housing is produced by selective laser-induced etching of fused silica.
For more than two decades, Raman spectroscopy has found widespread use in biological and medical applications. The instrumentation and the statistical evaluation procedures have matured, enabling the lengthy transition from ex-vivo demonstration to in-vivo examinations. This transition goes hand-in-hand with many technological developments and tightly bound requirements for a successful implementation in a clinical environment, which are often difficult to assess for novice scientists in the field. This review outlines the required instrumentation and instrumentation parameters, designs, and developments of fiber optic probes for the in-vivo applications in a clinical setting. It aims at providing an overview of contemporary technology and clinical trials and attempts to identify future developments necessary to bring the emerging technology to the clinical end users. A comprehensive overview of in-vivo applications of fiber optic Raman probes to characterize different tissue and disease types is also given.
Raman spectroscopy has been proven to have tremendous potential as biomedical analytical tool for spectroscopic disease diagnostics. The use of fiberoptic coupled Raman spectroscopy systems can enable in-vivo characterization of suspicious lesions. However, Raman spectroscopy has the drawback of rather long acquisition times of several hundreds of milliseconds which makes scanning of larger regions quite challenging. By combining Raman spectroscopy with a fast imaging technique this problem can be alleviate in part. Fluorescence lifetime imaging (FLIm) offers a great potential for such a combination. FLIm can allow for fast tissue area pre-segmentation and location of the points for Raman spectra acquisition. Here, we introduce an optical fiber probe combining FLIm and Raman spectroscopy with an outer diameter of 2 mm. Fluorescence is generated via excitation with a fiber laser at 355 nm. The fluorescence emission is spectrally resolved using a custom-made wavelength-selection module (WSM). The Raman excitation power at 785 nm was set to 50 mW for the in-vivo measurements to prevent sample drying. The lateral probe resolution was determined to be <250 μm for both modalities. This value was taken as step size for several raster scans of different tissue types which were conducted to show the overlap of both modalities under realistic conditions. Finally the probe was used for in vivo raster scans of a rat’s brain and subsequently to acquire FLIm guided Raman spectra of several tissues in and around the craniotomy.
Fiber Bragg gratings as key components in telecommunication, fiber lasers, and sensing systems usually rely on the Bragg condition for single mode fibers. In special applications, such as in biophotonics and astrophysics, high light coupling efficiency is of great importance and therefore, multimode fibers are often preferred. The wavelength filtering effect of Bragg gratings in multimode fibers, however is spectrally blurred over a wide modal spectrum of the fiber. With a well-designed all solid multicore microstructured fiber a good light guiding efficiency in combination with narrow spectral filtering effect by Bragg gratings becomes possible.
The combination of Raman spectroscopy with fiber optic probes enables analyzing the biochemical composition of tissues without markers in a non-destructive way. A small diameter (1 mm) fiber optic probe with one excitation fiber, 11 detection fibers and integrated filters (Emvision, USA) was recently coupled to a Raman spectrometer (Kaiser Optical Systems) to study excised arteries ex vivo and rabbit arteries in vivo. The current contribution introduces a novel fiber optic Raman probe with in-line fiber Bragg gratings (FBGs) as notch filter in the collection path. Multi-core single-mode fibers (MCSMF) were drawn integrating 19 and 61 single-mode cores to improve collection efficiency. Raman probes were assembled with one fiber for excitation and six MCSMF with inscribed FBGs for collection. The diameter of the 6 around 1 geometry can be reduced down to 0.375 mm. Background suppression, collection efficiency and distance dependence of the probes were characterized and first Raman measurements are presented. The advantages of the novel probes are discussed and further applications to Raman-on-chip detection schemes are described.
The hand-foot-syndrome presents a severe dermal side-effect of chemotherapeutic cancer treatment.
The cause of this side-effect is the elimination of systemically administered chemotherapeutics with
the sweat. Transported to the skin surface, the drugs subsequently penetrate into the skin in the
manner of topically applied substances. Upon accumulation of the chemotherapeutics in the skin the
drugs destroy cells and tissue - in the same way as they are supposed to act in cancer cells.
Aiming at the development of strategies to illuminate the molecular mechanism underlying the handfoot-
syndrome (and, in a second step, strategies to prevent this severe side-effect), it might be
important to evaluate the concentration and distribution of chemotherapeutics and antioxidants in the
human skin. The latter can be estimated by the carotenoid concentration, as carotenoids serve as
marker substances for the dermal antioxidative status.Following the objectives outlined above, this contribution presents a spectroscopic study aiming at
the detection and quantification of carotenoids and selected chemotherapeutics in human skin. To
this end, spontaneous Raman scattering and coherent anti-Stokes Raman scattering (CARS)
microspectroscopy are combined with two-photon excited fluorescence. While the latter technique is
Please verify that (1) all pages are present, (2) all figures are correct, (3) all fonts and special characters are correct, and (4) all text and figures fit within the red
margin lines shown on this review document. Complete formatting information is available at http://SPIE.org/manuscripts
Return to your MySPIE To Do List at http://myspie.org and approve or disapprove this submission. Your manuscript will not be published without this approval.restricted to the detection of fluorescent chemotherapeutics, e.g., doxorubicin, the vibrational
spectroscopic techniques can - in principle - be applied to any type of analyte molecules.
Furthermore, we will present the monitoring of doxorubicin uptake during experiments.
Nonlinear optical imaging techniques based e.g. on coherent anti-Stokes Raman scattering (CARS) or second-harmonic
generation (SHG) show great potential for in-vivo investigations of tissue. While the microspectroscopic imaging tools
are established, automized data evaluation, i.e. image pattern recognition and automized image classification, of
nonlinear optical images still bares great possibilities for future developments towards an objective clinical diagnosis.
This contribution details the capability of nonlinear microscopy for both 3D visualization of human tissues and
automated discrimination between healthy and diseased patterns using ex-vivo human skin samples. By means of CARS
image alignment we show how to obtain a quasi-3D model of a skin biopsy, which allows us to trace the tissue structure
in different projections. Furthermore, the potential of automated pattern and organization recognition to distinguish
between healthy and keloidal skin tissue is discussed. A first classification algorithm employs the intrinsic geometrical
features of collagen, which can be efficiently visualized by SHG microscopy. The shape of the collagen pattern allows
conclusions about the physiological state of the skin, as the typical wavy collagen structure of healthy skin is disturbed
e.g. in keloid formation. Based on the different collagen patterns a quantitative score characterizing the collagen
waviness - and hence reflecting the physiological state of the tissue - is obtained. Further, two additional scoring
methods for collagen organization, respectively based on a statistical analysis of the mutual organization of fibers and on
FFT, are presented.
Optical microspectroscopic tools reveal great potential for dermatologic diagnostics in the clinical day-to-day routine. To
enhance the diagnostic value of individual nonlinear optical imaging modalities such as coherent anti-Stokes Raman
scattering (CARS), second harmonic generation (SHG) or two-photon excited fluorescence (TPF), the approach of
multimodal imaging has recently been developed. Here, we present an application of nonlinear optical multimodal
imaging with Raman-scattering microscopy to study sizable human-tissue cross-sections. The samples investigated
contain both healthy tissue and various skin tumors.
This contribution details the rich information content, which can be obtained from the multimodal approach: While
CARS microscopy, which - in contrast to spontaneous Raman-scattering microscopy - is not hampered by single-photon
excited fluorescence, is used to monitor the lipid and protein distribution in the samples, SHG imaging selectively
highlights the distribution of collagen structures within the tissue. This is due to the fact, that SHG is only generated in
structures which lack inversion geometry. Finally, TPF reveals the distribution of autofluorophores in tissue. The
combination of these techniques, i.e. multimodal imaging, allows for recording chemical images of large area samples
and is - as this contribution will highlight - of high clinically diagnostic value.
A basic problem intrinsic to many clinical diagnostic procedures as well as minimally invasive surgeries is the online invivo
classification of tissue. Associated with this problem is the task to determine the boundaries between tissue sections
of various degrees of disease progression, which cannot be identified easily. This problem is partly founded in the
imaging modalities conventionally used, i.e., white-light endoscopy or fluorescence-based endoscopic imaging. These
techniques allow for extracting of only a limited parameter set for judging the physiological or pathological state of
tissue. Furthermore, fluorescence-based endoscopy relies on the administration of external labels, which principally
disturbs the native tissue.
These problems can be circumvented using Raman microspectroscopy as a diagnostic tool. Raman microscopy allows to
record vibrational spectra at each sampling point. Therefore the molecular fingerprint of the sample can be deciphered
with spatial resolution. It has been shown that Raman spectroscopy in combination with advanced statistical
methods can be used to identify and grade tissue samples. However, the conventional approach of judging excised tissue
sections by Raman microscopy does not present an approach which can be readily used in the clinics.
Here we present our recent progress towards designing a fiber-based Raman probe, which - in perspective - might be
incorporated into the working channel of a surgical endoscope. Thereby, it is anticipated to contribute to the clinical
routine. We will review the general design principle of such a device and the specific design strategy for our Raman
probe in concert with comparative measurements employing a set of home-built and commercially-available devices.
Microstructured optical fibers (MOFs) represent a promising platform technology for new biosensing devices. Using
MOFs with adapted cavity diameters of about 20 to 30 μm, they can be used to carry the biofluids of analytical interest.
Such cavities with their walls coated by transducer material form in combination with adequate microfluidic chips a
platform for fully integrated next generation plasmonic devices. This paper describes the use of a dynamic chemical
nanoparticle layer deposition (NLD) technique to demonstrate the wet chemical deposition of gold and silver
nanoparticles (NP) within MOFs with longitudinal, homogenously-distributed particle densities. The plasmonic
structures were realized on the internal capillary walls of a three-hole suspended core fiber. Electron micrographs, taken
of the inside of the fiber holes, confirm the even distribution of the NP. With the proposed procedure fiber lengths of
several meters can be coated and afterwards cut up into small pieces of desired lengths. Accordingly, this procedure is
highly productive and makes the resulting MOF-based sensors potentially cost efficient. In proof-of-principle
experiments with liquids of different refractive indices, the dependence of the localized surface plasmon resonance
(LSPR) on the surroundings was confirmed. Comparing Raman spectra of NP coated and uncoated MOFs, each filled
with crystal violet, a significant signal enhancement demonstrates the usability of such functionalized MOFs for surfaceenhanced
Raman spectroscopy (SERS) experiments.
We present combined coherent anti Stokes Raman scattering and two-photon excited fluorescence microscopy, for label-free
in vitro and in vivo imaging of skin with both chemical discrimination and subcellular resolution. In particular, we
show how CARS microscopy is utilized to image lipid-rich structures inside the skin, preparing for a combined
multiphoton and CARS imaging modality for biomedical research and skin imaging. As a further potential application
the detection of topically applied oil on the skin is presented.
Microstructured optical fibers (MOFs) represent a promising platform technology for fully integrated, next generation
plasmonic devices. This paper details the use of a dynamic chemical deposition technique to demonstrate the wet
chemical deposition of gold and silver nanoparticles (NP) within MOFs with longitudinal, homogenously-distributed
particle densities. The plasmonic structures were realized on the internal capillary walls of a three-hole suspended core
fiber. The population density of the NP on the surface, which directly influences the usable / necessary sensor length, can
be tailored via the controlled pre-treatment of the fiber. With the proposed procedure we can coat several meters of fiber
and, afterwards, cut the fiber into the desired lengths. Accordingly, this procedure is highly productive and makes the
resulting MOF-based sensors potentially very cheap. Electron microscope micrographs, taken of the inside of the fiber
holes, confirm the even distribution of the NP. A transversal through-light setup was used for the non-destructive layer
characterization. In proof-of-principle experiments with liquids of different refractive indices, the LSPR dependence on
the surroundings was confirmed and compared with Mie-theory based calculations.
Advantages of optical fiber Bragg grating sensors at low temperatures, are electrical isolation, low electro-magnetic interference,
low thermal conductivity to a large number of multiplexed sensors. They show negligible thermo-optic and magnetooptic
effects in cryogenic environment. These properties make them attractive for temperature surveillance and structural
health monitoring of cryogenic systems, or for the testing of material properties and system components at low temperatures.
Their small size, the multiplexing capability, and the high elasticity of glass fiber can provide reasons to use optical fiber
temperature sensors instead of approved conventional thermo couples for temperature monitoring of hot gas turbine
components.
Large power engines are permanently increasing efficiency. Knowledge of thermal and mechanical loads is
getting important. A novel coupling technique allows to interrogate FBG temperature and strain sensors on
rotating parts which are normally not accessible.
It has been demonstrated that Fiber Bragg Grating Sensors can measure at very low temperatures in Helium
cryostats. The intrinsic temperature sensitivity is very low but can be significantly enhance by the thermal
expansion of polymer carriers. Temperature and mechanical strain changes can be measured quite accurately.
For applications over a wide temperature range, it is important to know the temperature effect on certain material
parameters, as e.g., Young's modulus, reversibility of elastic deformations, or coefficient of thermal expansion.
Especially at cryogenic temperatures, the low temperature dependence of the Bragg wavelength is advantageous for
measuring strain effects. It was already demonstrated that fiber Bragg gratings can be used to measure the coefficient of
thermal expansion of super-conducting materials [1]. In this paper, we present a method for the measurement of the
temperature dependent changes of Young's modulus, down to temperatures of 4.2 K (liquid helium). Deformation
samples made of CuBe bronze have been prepared for first tests showing best reversibility.
While conventional resistance strain gages show increasing cross-sensitivities to temperature and magnetic field with decreasing temperature down to liquid helium, it has been found that fiber optic Bragg grating strain sensors show negligible thermo-optic and magneto-optic effects in cryogenic environment and allow, therefore, reliable strain measurements.
These specific application advantages of optical fiber Bragg grating sensors at low temperatures, together with the electrical isolation and low electro-magnetic interference, low thermal conductivity to a large number of multiplexed sensors, make them attractive for structural health monitoring of super-conductive magnets, e.g., for super-conductive motors, magnetic levitation transport, nuclear fusion reactors, or for measurement of material parameters at low temperature, and, if using special sensor substrates, also for temperature measurements and hot spot detection on superconductors.
Knowledge of the gas flow distributions, their mass velocity and turbulences, in chemical reactors, thermodynamic
engines, pipes, and other industrial facilities may help to achieve a more efficient system performance.
In our novel approach, optical fibre Bragg grating (FBG) sensors have been used for measuring the temperature of a
heated element, adapting the principles of conventional hot-wire-anemometers. Because of the multiplexing capability
of FBG sensors, the gas mass flow distribution can be measured along the sensor array. The length of the heated and
sensor-equipped element can be easily adapted to the cross section of the gas flow, from <10 cm up to several metres.
The number and distances of FBGs distributed over this length defines the spatial resolution and is basically limited by
the sensor signal processing. According to FBG sensor lengths < 5 mm, spatial resolutions of gas flow measurements of
less than 1 cm can be achieved.
We propse the application of sensors based on the intrinsic bend sensitivity of Bragg gratings inscribed in D-shaped fibers. The first example is a viscosity sensor, consisting of the D-shaped fiber with a sphere attached to the tip of the fiber. The force exerted on the sphere by the laminar flow of a fluid with unknown viscosity bends the fiber, and with this shifts the Bragg wavelength of the inscribed Bragg grating. The other one is a hydrogen senosr, which uses the influence of hydrogen on a palladium foil attached to the Bragg grating. The palladium foil, which is frictionally connected to the flat surface of the D-shaped fiber, is stretched under the influence of hydrogen and with this stretches/bends the fiber.
Sensors for the detection of hydrogen, which is very volatile, extremely flammable and highly explosive, are needed in many fields, for example in nuclear power plants, in launch vehicles for human space flight, in hydrogen production plants, and fuel cells. To enhance the safety level it seems appropriate to use optical sensors instead of electronic ones.
In the presentation, investigations concerning the use of fiber optic Bragg grating (FBG) sensors as part of the surveillance system of liquid fuel tanks will be described. The sensors are supposed to measure strain and temperature when embedded in the inner tank wall and to detect hydrogen leakage. To fulfill this task the temperature and strain sensors have to prove their functionality down to minimum temperatures of 20K.
As the dn/dT for quartz decreases to very low values, the FBG temperature transducer has to be bonded to a substrate with sufficiently high coefficient of thermal expansion also under cryogenic conditions. As the only applicable solution a high-expansion glass has been found, which in connection with specific fiber coating and bonding materials for the strain-transducer fulfils all the sensor requirements.
The hydrogen sensor utilizes the expansion of palladium in an atmosphere containing hydrogen and consists in our new sensor configuration of a palladium foil bonded to a special-shaped fiber. Experimental results for concentration ranges 0-4%vol H2 and temperature ranges from -40°C to +80°C show the parameters of application of a hydrogen leakage detection system.
A temperature sensor network basing on 20 multiplexed fiber Bragg gratings has been developed to perform gas temperature distribution monitoring within the 60-m diameter helium gas fill of a novel cargo airship CL75 for loads of up to 75 metric tons providing a long-term repeatability of temperature measuring results of 0.15 K. The fiber optic temperature sensors overcome problems with lightning protection in the all-plastic airship and allow to measure true gas temperatures through the whole balloon volume. The gas temperature data of the sensor network are used in airship lifting control to improve the flight height stabilization.
A fiber Bragg grating (FBG) sensor network has been developed for structural health monitoring on board of the X-38 spacecraft, the prototype of a crew return vehicle for the International Space Station. The FBG sensors will monitor mechanical and thermal load profiles of a frame component during launch and re-entry of the spacecraft. Four sensor pads are interrogated which contain three Bragg gratings each for 2D orthogonal strain and temperature measurements. The requirements for mechanical and thermal stability under the demanding conditions of vibration and shock loads, at temperatures within -40..+200 degree(s)C, have been fulfilled applying appropriate fiber passivation and Ormocer re-coating techniques, and by the development of a robust polychromator based signal processing unit.
The exploitation of surface plasmon resonance (SPR) sensing principle for the study of formation of multilayers of human immunoglobulin (hlgG) and monoclonal antibody against human choriogonadotropin (a-hCG) as well as for monitoring immunoreaction between the immobilized a-hCG and human choriogonadotropin (hCG) is reported. It is demonstrated that even a very small attachment of proteins (due to the adsorption or the specific interaction) may be detected by the presented SPR sensor. An immobilization technique is described which allows to form stable multilayers of antibodies on the gold surface.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.