Breath analysis is an attractive non-invasive strategy for early disease recognition or diagnosis, and for therapeutic progression monitoring, as quantitative compositional analysis of breath can be related to biomarker panels provided by a specific physiological condition invoked by e.g., pulmonary diseases, lung cancer, breast cancer, and others. As exhaled breath contains comprehensive information on e.g., the metabolic state, and since in particular volatile organic constituents (VOCs) in exhaled breath may be indicative of certain disease states, analytical techniques for advanced breath diagnostics should be capable of sufficient molecular discrimination and quantification of constituents at ppm-ppb - or even lower - concentration levels. While individual analytical techniques such as e.g., mid-infrared spectroscopy may provide access to a range of relevant molecules, some IR-inactive constituents require the combination of IR sensing schemes with orthogonal analytical tools for extended molecular coverage. Combining mid-infrared hollow waveguides (HWGs) with luminescence sensors (LS) appears particularly attractive, as these complementary analytical techniques allow to simultaneously analyze total CO2 (via luminescence), the 12CO2/13CO2 tracer-to-tracee (TTR) ratio (via IR), selected VOCs (via IR) and O2 (via luminescence) in exhaled breath, yet, establishing a single diagnostic platform as both sensors simultaneously interact with the same breath sample volume. In the present study, we take advantage of a particularly compact (shoebox-size) FTIR spectrometer combined with novel substrate-integrated hollow waveguide (iHWG) recently developed by our research team, and miniaturized fiberoptic luminescence sensors for establishing a multi-constituent breath analysis tool that is ideally compatible with mouse intensive care stations (MICU). Given the low tidal volume and flow of exhaled mouse breath, the TTR is usually determined after sample collection via gas chromatography coupled to mass spectrometric detection. Here, we aim at potentially continuously analyzing the TTR via iHWGs and LS flow-through sensors requiring only minute (< 1 mL) sample volumes. Furthermore, this study explores non-linearities observed for the calibration functions of 12CO2 and 13CO2 potentially resulting from effects related to optical collision diameters e.g., in presence of molecular oxygen. It is anticipated that the simultaneous continuous analysis of oxygen via LS will facilitate the correction of these effects after inclusion within appropriate multivariate calibration models, thus providing more reliable and robust calibration schemes for continuously monitoring relevant breath constituents.
We present a new class of surface-enhanced Raman scattering (SERS) substrates based on lithographically-defined two-dimensional
rectangular array of nanopillars. Two types of nanopillars within this class are discussed: vertical pillars and
tapered pillars. For the vertical pillars, the gap between each pair of nanopillars is small enough (< 50 nm) such that
highly confined plasmonic cavity resonances are supported between the pillars when light is incident upon them, and the
anti-nodes of these resonances act as three-dimensional hotspots for SERS. For the tapered pillars, SERS enhancement
arises from the nanofocusing effect due to the sharp tip on top. SERS experiments were carried out on these substrates
using various concentrations of 1,2 bis-(4-pyridyl)-ethylene (BPE), benzenethiol (BT) monolayer and toluene vapor. The
results show that SERS enhancement factor of over 0.5 x 109 can be achieved, and BPE can be detected down to femto-molar
concentration level. The results also show promising potential for the use of these substrates in environmental
monitoring of gases and vapors such as volatile organic compounds.
The Raman analysis of common, non-absorbing gases was performed using an 18@1 fiber-optic probe coupled to a
multi-pass capillary cell (MCC) for signal enhancement. The MCC is fabricated by metal-coating, using silver or other
highly reflective metals, the inside of a 1-2 mm diameter glass capillary using commercially available silvering solutions
and provides enhancements up to 30-fold over measurements using the fiber-optic probe alone. The design of the MCC
is simple and the device is easy to incorporate into an experimental setup making it suitable for remote and <i>in-situ</i>
analysis. Although the MCC is functionally similar to liquid-core waveguides that have been previously described in the
literature, the MCC is not based on total internal reflection and so the refractive index of the analyte is not important to
the operation of the device. The principle of operation of the MCC is similar to mirror-based multiple pass Raman cells,
however, the MCC is not expensive, alignment is trivial and an optical path length up to several meters in length is
possible. With our first-generation silver-coated MCCs, limits of detection were determined to be 0.02% and 0.2% for
CH4 and CO2 respectively. In this talk we will discuss optimization of the MCC and issues involved in its use.
One of the strengths of laser-induced breakdown spectroscopy (LIBS) is the ability to acquire atomic emission spectra for a wide variety of samples non-invasively, with only optical access being required. The use of optical fibers makes the technique ideal for applications where the measurement area of interest is either not accessible or where it is not safe to take a sample. Fiber-optic LIBS probes have been described where a single laser pulse is delivered to the sampling region by one optical fiber and the emission is collected by another. One of the problems with this approach is fiber degradation from the high power laser pulses. To minimize this problem, we are investigating dual-pulse LIBS where the laser power is split between 2 different laser pulses that are separated by a short delay time. We have found in related studies that the use of dual laser pulses to obtain LIBS signals can lead to enhanced intensity and reproducibility for some types of samples. A natural extension of this result is to make dual- pulse measurements using optical fibers. Thus far, we have seen 1.5 to 2 fold enhancements for copper and lead using fiber-optics in various geometries to both deliver the dual laser pulses and collect the emission.
Recent work performed in this laboratory has demonstrated the feasibility of using tunable filter technologies in place of dispersive spectrometers and fixed filtering devices for the purpose of creating field transportable standoff Raman imaging systems. Recently, a development in the area of polymer science has led to the production of polymer mirrors which are lightweight compared to glass mirrors of similar size. In addition, the techniques used to produce these polymer mirrors make it easy to design low f/pound optical devices, with much higher optical speeds than identically sized glass mirrors. The performance of a low f/pound polymer mirror system in combination with a liquid crystal tunable filter for standoff Raman chemical imaging is demonstrated and evaluated.
We are investigating the use of small, transportable, Raman systems for remote Raman measurements at intermediate ranges. Previous work focused on the use of an imaging spectrograph and a fiber-optic coupled probe for making single point measurements. More recently we have considered the use of tunable filters for remote Raman imaging. For this work, acousto-optical and liquid crystal tunable filters are being used both with, an in place of dispersive spectrometers and fixed filtering devices. In addition, we have improved the system by the use of a modified holographic fiber-optic Raman probe for light and image collection. In these experiments, a 100 micron collection optical fiber is replaced with a small diameter image guide for light collection and imaging. The feasibility of tunable filter technology for remote Raman imagin will be discussed along with the merits of image transfer devices using small- diameter image guides.
Fiber-optic chemical sensors (FOCS's) are useful for making remote, in-situ, and microscale measurements. Many intensity-based and lifetime-based FOCS's have been developed for a wide range of properties and analytes. Most of these sensors give only a single-point measurement however, recently a few intensity based imaging FOCS's have been described. We have developed intensity-based fiber- optic imaging systems to measure the transport of water in thin NafionTM membranes and to monitor the development of pH gradients at the surface of an electrode during electrolysis of water. However, intensity-based measurements are difficult to calibrate because of the dependence of luminescence intensity on many interfering factors including dye concentration and varying excitation intensity. As a result, we are developing lifetime-based fiber-optic imaging sensors for a variety of applications. At this point we have measured a lifetime image across a sol-gel crack using a fiber-optic image guide to carry the excitation light to the sample and the resulting luminescence image to an ICCD. Currently, we are testing an oxygen imaging FOCS to capture lifetime-based images of at least two different lifetimes. This paper describes the single-point, lifetime-based sensors we have developed as precursors to fiber-optic imaging chemical sensors, the intensity-based imaging studies of water transport in thin NafionTM membranes and the development of pH gradients at electrode surfaces. It also discusses the instrumental system and methods used to collect lifetime images of sol-gel cracks with a fiber- optic, and the preliminary results of our imaging oxygen sensor.
Fiber-optic imaging sensors are being developed for in-situ chemical measurements using microfiber image guides. Applications of particular interest are analyte transport in thin membranes and ion transport in electrochemical boundary layers. We have demonstrated that microfiber image guides can be used for in-situ transport studies of analyte transport in thin membranes and for ion transport at electrode boundary layers in a working electrochemical cell. We have also shown that imaging sensors can be made by coating the image guide with pH sensitive and other ion- sensitive fluorescent indicator molecules, and that these sensors can be used to measure the time development of concentration gradients in-situ. Finally, it is demonstrated that these techniques can be used to obtain fundamental transport information such as diffusion coefficients in-situ at the microscopic level. Image guide sensors are described here along with a discussion of preliminary transport studies.