Homogeneity Measurements of Li-Ion Battery Cathodes Using Laser-Induced Breakdown Spectroscopy.

We study the capability of nanosecond laser-induced breakdown spectroscopy (ns-LIBS) for depth-resolved concentration measurements of Li-Ion battery cathodes. With our system, which is optimized for quality control applications in the production line, we pursue the goal to unveil manufacturing faults and irregularities during the production process of cathodes as early as possible. Femtosecond laser-induced breakdown spectroscopy (fs-LIBS) is widely considered to be better suited for depth-resolved element analysis. Nevertheless, the small size and intensity of the plasma plume, non-thermal energy distribution in the plasma and high investment costs of fs-LIBS make ns-LIBS more attractive for inline application in the industrial surrounding. The system, presented here for the first time, is able to record quasi-depth-resolved relative concentration profiles for carbon, nickel, manganese, cobalt, lithium and aluminum which are the typical elements used in the binder/conductive additive, the active cathode material and the current collector. LIBS often causes high variations in signal intensity from pulse to pulse, so concentration determination is, in general, conducted on the average of many pulses. We show that the spot-to-spot variations we measure are governed by the microstructure of the cathode foil and are not an expression of the limited precision of the LIBS setup.

Laser-guided real-time automatic target identification for endoscopic stone lithotripsy: a two-arm in vivo porcine comparison study.

INTRODUCTION AND OBJECTIVE: Thermal injuries associated with Holmium laser lithotripsy of the urinary tract are an underestimated problem in stone therapy. Surgical precision relies exclusively on visual target identification when applying laser energy for stone disintegration. This study evaluates a laser system that enables target identification automatically during bladder stone lithotripsy, URS, and PCNL in a porcine animal model. METHODS: Holmium laser lithotripsy was performed on two domestic pigs by an experienced endourology surgeon in vivo. Human stone fragments (4-6 mm) were inserted in both ureters, renal pelvises, and bladders. Ho:YAG laser lithotripsy was conducted as a two-arm comparison study, evaluating the target identification system against common lithotripsy. We assessed the ureters' lesions according to PULS and the other locations descriptively. Post-mortem nephroureterectomy and cystectomy specimens were examined by a pathologist. RESULTS: The sufficient disintegration of stone samples was achieved in both setups. Endoscopic examination revealed numerous lesions in the urinary tract after the commercial Holmium laser system. The extent of lesions with the feedback system was semi-quantitatively and qualitatively lower. The energy applied was significantly less, with a mean reduction of more than 30% (URS 27.1%, PCNL 52.2%, bladder stone lithotripsy 17.1%). Pathology examination revealed only superficial lesions in both animals. There was no evidence of organ perforation in either study arm. CONCLUSIONS: Our study provides proof-of-concept for a laser system enabling automatic real-time target identification during lithotripsy on human urinary stones. Further studies in humans are necessary, and to objectively quantify this new system's advantages, investigations involving a large number of cases are mandatory.

Quantitative Measurement of Fluorescent Layers with Respect to Spatial Thickness Variations and Substrate Properties.

Imaging fluorescence spectroscopy proves to be a fast and sensitive method for measuring the thickness of thin coatings in the manufacturing industry. This encouraged us to systematically study, theoretically and experimentally, parameters that influence the fluorescence of thin layers. We analyzed the fluorescence signal as a function of the scattering and reflectance properties of the sample substrate. In addition, we investigated effects of the layer properties on fluorescence emission. A ray-tracing software is used to describe the influence of these parameters on the fluorescence emission of thin layers. Experiments using a custom-made system for imaging fluorescence analysis verify the simulations. This work shows a factor five variation of fluorescence intensity as a function of the reflectance of the sample substrate. Simulations show variations by a factor of up to eight for samples with different surface roughness. Results on tilted samples indicate a significant increase of the detected fluorescence signal, for fluorescent droplets on reflective substrates, if illuminated and coaxially observed at angles greater than 25°. These findings are of utmost relevance for all applications which utilize the fluorescence emission to quantify thin layers. These applications range from in-line lubricant monitoring in press plants to monitoring of functional coatings in medical technology and the detection of filmic contaminations.

Calibration of systems for quantitative fluorescence analysis of thin layers.

Imaging fluorescence analysis is a powerful tool for the characterization of thin functional layers. Due to the development of new components such as cost-efficient and long life diode lasers and LEDs as well as sensitive cameras, the number of industrial in situ sensors based on fluorescence analysis technology increased rapidly in recent years. Of crucial importance for all these new sensors are efficient and robust methods for calibration. Although there are many examples for the calibration of laboratory setups for single specialized applications, there is no standardized method for the traceable device independent calibration of imaging fluorescence systems. This paper presents the evaluation of five different methods for the calibration of systems for quantitative fluorescence analysis. Each method is applied for the calibration of an imaging fluorescence laser scanner. In addition to characterizing the precision of the methods, the work analyzes the usability of the methods for different applications. The results show for the first time that a calibrated IR point sensor can be used for the auto calibration of high resolution imaging inline fluorescence sensors. In addition, we present a novel method for the transfer of calibration data between analysis systems with different optical setups by using a solid material fluorescence standard.

Comparison of Laser Pulse Duration for the Spatially Resolved Measurement of Coating Thickness with Laser-Induced Breakdown Spectroscopy.

In this study, a method is presented to measure precisely the thickness of coated components based on laser-induced breakdown spectroscopy (LIBS). The thickness is determined by repetitively ablating the coating with ultrashort laser pulses, monitoring the spectrum of the generated plasma and calculating the coating thickness from the specific plasma signal in comparison to a reference measurement. We compare different pulse durations of the laser (290 fs, 10 ps, 6 ns) to extend the material analysis capabilities of LIBS to a real thickness measurement tool. The method is designed for production processes with known coating materials. Here, we show this for a nickel coating and a tungsten carbide coating on a copper sample with thicknesses from 5-30 µm.

A Novel Laser Lithotripsy System with Automatic Real-Time Urinary Stone Recognition: Computer Controlled Ex Vivo Lithotripsy is Feasible and Reproducible in Endoscopic Stone Fragmentation.

PURPOSE: Urinary stone treatment has been strongly influenced by advances in technology. Nevertheless, the photonic characteristics of stones as the treatment target have been neglected. Monitoring fluorescence spectra is sufficient for automatic target differentiation and laser feedback control as previously described. We investigated the characteristics of fluorescence signals and the clinical practicability of real-time laser feedback control during lithotripsy. MATERIALS AND METHODS: Fluorescence excitation light was superimposed on a holmium laser beam into the treatment fiber. Spectra were recorded and signal amplitude changes were analyzed during increases in distance between the fiber tip and the stone to identify the optimal threshold level for stone recognition. Ho:YAG lithotripsy was performed under in vitro surgical conditions in porcine tissue while our feedback system autonomously controlled the laser impulse release during lithotripsy. The tissue was then endoscopically and macroscopically examined for laser induced lesions. RESULTS: Mean ± SD autofluorescence signal amplitudes from urinary stone samples varied between 142 ± 29 and 1,521 ± 152 ADU while tissue and endoscope coating emission was negligible. Signal amplitude decreased rapidly at distances larger than 1 to 2 mm. Clinically reliable threshold values for target recognition could be set to prevent laser pulse emission if the stone was out of range or urothelial tissue might be harmed by laser irradiation. We observed no incorrectly released laser pulse or injury to tissue during autonomously controlled holmium laser lithotripsy. CONCLUSIONS: Our laboratory study strengthens the evidence that tracking real-time autofluorescence spectra during endoscopic stone surgery via automatic feedback control of the laser impulse release may become a potentially useful clinical tool for surgeons who navigate in the upper urinary tract.

Experimental Evaluation of Human Kidney Stone Spectra for Intraoperative Stone-Tissue-Instrument Analysis Using Autofluorescence.

PURPOSE: The precision and safety of laser lithotripsy in the upper urinary tract is solely controlled by the surgeon. To our knowledge laser systems with integrated real-time analysis of target tissues are not available. An intelligent laser system with automated target differentiation and laser feedback control would provide tremendous improvement in patient safety and surgical precision. We evaluated the technical, medical and physical conditions for real-time analysis using fluorescence for future development of a new laser for lithotripsy. MATERIALS AND METHODS: We collected data on the fluorescence spectra of 82 native human calculi covering the 8 most relevant subtypes compared to the spectra of endoscope components, the organic porcine urinary tract and pure samples of urinary stone compositions. Data analysis was performed to determine differences in sample signal intensities and emission wavelengths. RESULTS: All native stones showed a significant fluorescence signal compared to porcine urinary tract tissue or endoscope components. The amplitude of the fluorescence signal varied by a factor of 75. The weakest signal of stone material was 3.6-fold larger than the strongest signal of pig kidney tissue (mean ± SD 0.038 ± 0.043 vs 0.00058 ± 0.00058 arbitrary units). No fluorescence signal was observed for endoscope components. Fluorescence amplitude and spectral curve form were found to be unrelated to stone type. CONCLUSIONS: Our study provides essential information on the spectral differentiation of tissue, urinary stones and relevant endoscope components. The measurements indicate that differentiation by fluorescence is possible for all relevant stone types.

Highly-integrated lab-on-chip system for point-of-care multiparameter analysis.

A novel innovative approach towards a marketable lab-on-chip system for point-of-care in vitro diagnostics is reported. In a consortium of seven Fraunhofer Institutes a lab-on-chip system called "Fraunhofer ivD-platform" has been established which opens up the possibility for an on-site analysis at low costs. The system features a high degree of modularity and integration. Modularity allows the adaption of common and established assay types of various formats. Integration lets the system move from the laboratory to the point-of-need. By making use of the microarray format the lab-on-chip system also addresses new trends in biomedicine. Research topics such as personalized medicine or companion diagnostics show that multiparameter analyses are an added value for diagnostics, therapy as well as therapy control. These goals are addressed with a low-cost and self-contained cartridge, since reagents, microfluidic actuators and various sensors are integrated within the cartridge. In combination with a fully automated instrumentation (read-out and processing unit) a diagnostic assay can be performed in about 15 min. Via a user-friendly interface the read-out unit itself performs the assay protocol, data acquisition and data analysis. So far, example assays for nucleic acids (detection of different pathogens) and protein markers (such as CRP and PSA) have been established using an electrochemical read-out based on redoxcycling or an optical read-out based on total internal reflectance fluorescence (TIRF). It could be shown that the assay performance within the cartridge is similar to that found for the same assay in a microtiter plate. Furthermore, recent developments are the integration of sample preparation and polymerase chain reaction (PCR) on-chip. Hence, the instrument is capable of providing heating-and-cooling cycles necessary for DNA-amplification. In addition to scientific aspects also the production of such a lab-on-chip system was part of the development since this heavily affects the success of a later market launch. In summary, the Fraunhofer ivD-platform covers the whole value chain ranging from microfluidics, material and polymer sciences, assay and sensor development to the production and assembly design. In this consortium the gap between diagnostic needs and available technologies can be closed.

Rapid protein expression analysis with an interferometric biosensor for monitoring protein production.

The concentration of a recombinantly expressed protein has to be monitored to select optimal expression conditions throughout the protein production process. Today this is usually achieved semiquantitatively with sodium dodecyl sulfate polyacrylamide gel electrophoresis/western blotting or with ELISAs, which are time- and labor-intensive methods. In this paper the applicability of a label-free sensor system based on a Young interferometer is presented as an alternative for the monitoring of recombinant protein production. Once a protein is successfully produced, the interferometric biosensor allows any protein-protein interaction to be characterized in a label-free manner. This is demonstrated with an antibody/antigen pair, where the antibody is directed against a four-amino-acid tag used for protein expression analysis as well as purification during recombinant protein production. Label-free detection of the tagged protein is shown both in buffer and in bacterial cell lysate as a sample matrix. The system exhibiting a low limit of detection, low drift and reliable operation is compared with a commercial surface plasmon resonance sensor and a competitive ELISA.

Interferometric biosensor based on planar optical waveguide sensor chips for label-free detection of surface bound bioreactions.

A label free optical biosensor based on a free-space Young interferometer configuration is presented. Commercial planar Ta(2) O(5) waveguides are used as sensing elements and allow the investigation of surface bound bioreactions like immunoreactions or biological affinity systems. Design criteria are discussed and a detailed characterization of the sensor performance is presented. The developed interferometer yields an effective refractive index resolution of 9 x 10(-9), corresponding to a surface coverage of approximately 13 fg/mm(2). The performance of the system is characterized by two different affinity systems: the antibody-antigen complex protein G-immunoglobulin G is used as a model system for monitoring reaction kinetics. Further measurements on a silanized surface show the formation of a streptavidin monolayer on a biotinylated surface.

Noninvasive time-dependent cytometry monitoring by digital holography.

Using a digital holographic microscope setup, it is possible to measure dynamic volume changes in living cells. The cells were investigated time-dependently in transmission mode for different kinds of stimuli affecting their morphology. The measured phase shift was correlated to the cellular optical thickness, and then of the cell volume as well as the refractive index were calculated and interpreted. For the characterization of the digital holographic microscope setup, we have developed a transparent three-dimensional (3-D) reference chart that can be used as a lateral resolution chart and step-height resolution chart included in one substrate. For the monitoring of living cells, a biocompatible and autoclavable flow chamber was designed, which allows us to add, exchange, or dilute the fluid within the flow chamber. An integrated changeable coverslip enables inverse microscopic applications. Trypsinization, cell swelling and shrinking induced by osmolarity changes, and apoptosis served as model processes to elucidate the potential of the digital holographic microscopy (DHM).