Frequency-Resolved High-Frequency Broadband Measurement of Acoustic Longitudinal Waves by Laser-Based Excitation and Detection.

Optoacoustics is a metrology widely used for material characterisation. In this study, a measurement setup for the selective determination of the frequency-resolved phase velocities and attenuations of longitudinal waves over a wide frequency range (3-55 MHz) is presented. The ultrasonic waves in this setup were excited by a pulsed laser within an absorption layer in the thermoelastic regime and directed through a layer of water onto a sample. The acoustic waves were detected using a self-built adaptive interferometer with a photorefractive crystal. The instrument transmits compression waves only, is low-contact, non-destructive, and has a sample-independent excitation. The limitations of the approach were studied both by simulation and experiments to determine how the frequency range and precision can be improved. It was shown that measurements are possible for all investigated materials (silicon, silicone, aluminium, and water) and that the relative error for the phase velocity is less than 0.2%.

Guided Acoustic Waves in Polymer Rods with Varying Immersion Depth in Liquid.

Monitoring tanks and vessels play an important part in public infrastructure and several industrial processes. The goal of this work is to propose a new kind of guided acoustic wave sensor for measuring immersion depth. Common sensor types such as pressure sensors and airborne ultrasonic sensors are often limited to non-corrosive media, and can fail to distinguish between the media they reflect on or are submerged in. Motivated by this limitation, we developed a guided acoustic wave sensor made from polyethylene using piezoceramics. In contrast to existing sensors, low-frequency Hanning-windowed sine bursts were used to excite the L(0,1) mode within a solid polyethylene rod. The acoustic velocity within these rods changes with the immersion depth in the surrounding fluid. Thus, it is possible to detect changes in the surrounding media by measuring the time shifts of zero crossings through the rod after being reflected on the opposite end. The change in time of zero crossings is monotonically related to the immersion depth. This relative measurement method can be used in different kinds of liquids, including strong acids or bases.

Ultrasonic Interferometric Procedure for Quantifying the Bone-Implant Interface.

The loosening of an artificial joint is a frequent and critical complication in orthopedics and trauma surgery. Due to a lack of accuracy, conventional diagnostic methods such as projection radiography cannot reliably diagnose loosening in its early stages or detect whether it is associated with the formation of a biofilm at the bone-implant interface. In this work, we present a non-invasive ultrasound-based interferometric measurement procedure for quantifying the thickness of the layer between bone and prosthesis as a correlate to loosening. In principle, it also allows for the material characterization of the interface. A well-known analytical model for the superposition of sound waves reflected in a three-layer system was combined with a new method in data processing to be suitable for medical application at the bone-implant interface. By non-linear fitting of the theoretical prediction of the model to the actual shape of the reflected sound waves in the frequency domain, the thickness of the interlayer can be determined and predictions about its physical properties are possible. With respect to determining the layer's thickness, the presented approach was successfully applied to idealized test systems and a bone-implant system in the range of approx. 200 µm to 2 mm. After further optimization and adaptation, as well as further experimental tests, the procedure offers great potential to significantly improve the diagnosis of prosthesis loosening at an early stage and may also be applicable to detecting the formation of a biofilm.

Quantification of Humidity and Salt Detection in Historical Building Materials via Broadband Radar Measurement.

For the investigation of moisture and salt content in historic masonry, destructive drilling samples followed by a gravimetric investigation is still the preferred method. In order to prevent the destructive intrusion into the building substance and to enable a large-area measurement, a nondestructive and easy-to-use measuring principle is needed. Previous systems for moisture measurement usually fail due to a strong dependence on contained salts. In this work, a ground penetrating radar (GPR) system was used to determine the frequency-dependent complex permittivity in the range between 1 and 3 GHz on salt-loaded samples of historical building materials. By choosing this frequency range, it was possible to determine the moisture in the samples independently of the salt content. In addition, it was possible to make a quantitative statement about the salt level. The applied method demonstrates that with ground penetrating radar measurements in the frequency range selected here, a salt-independent moisture determination can be carried out.

On Dispersion Compensation for GAW-Based Structural Health Monitoring.

Guided acoustic waves (GAW) have proven to be a useful tool for structural health monitoring (SHM). However, the dispersive nature of commonly used Lamb waves compromises the spatial resolution making it difficult to detect small or weakly reflective defects. Here we demonstrate an approach that can compensate for the dispersive effects, allowing advanced algorithms to be used with significantly higher signal-to-noise ratio and spatial resolution. In this paper, the sign coherence factor (SCF) extension of the total focusing method (TFM) algorithm is used. The effectiveness is examined by numerical simulation and experimentally demonstrated by detecting weakly reflective layers with a highly dispersive A0 mode on an aluminum plate, which are not detectable without compensating for the dispersion effects.

Acoustic Limescale Layer and Temperature Measurement in Ultrasonic Flow Meters.

Guided acoustic waves are commonly used in domestic water meters to measure the flow rate. The accuracy of this measurement method is affected by factors such as variations in temperature and limescale deposition inside of the pipe. In this work, a new approach using signals from different sound propagation paths is used to determine these quantities and allow for subsequent compensation. This method evaluates the different propagation times of guided Lamb waves in flow measurement applications. A finite element method-based model is used to identify the calibration curves for the device under test. The simulated dependencies on temperature and layer thickness are validated by experimental data. Finally, a test on simulated data with varying temperatures and limescale depositions proves that this method can be used to separate both effects. Based on these values, a flow measurement correction scheme can be derived that provides an improved resolution of guided acoustic wave-based flow meters.

Elastic Properties Measurement Using Guided Acoustic Waves.

Nondestructive evaluation of elastic properties plays a critical role in condition monitoring of thin structures such as sheets, plates or tubes. Recent research has shown that elastic properties of such structures can be determined with remarkable accuracy by utilizing the dispersive nature of guided acoustic waves propagating in them. However, existing techniques largely require complicated and expensive equipment or involve accurate measurement of an additional quantity, rendering them impractical for industrial use. In this work, we present a new approach that requires only a pair of piezoelectric transducers used to measure the group velocities ratio of fundamental guided wave modes. A numerical model based on the spectral collocation method is used to fit the measured data by solving a bound-constrained nonlinear least squares optimization problem. We verify our approach on both simulated and experimental data and achieve accuracies similar to those reported by other authors. The high accuracy and simple measurement setup of our approach makes it eminently suitable for use in industrial environments.

Monitoring of Soft Deposition Layers in Liquid-Filled Tubes with Guided Acoustic Waves Excited by Clamp-on Transducers.

The monitoring of liquid-filled tubes with respect to the formation of soft deposition layers such as biofilms on the inner walls calls for non-invasive and long-term stable sensors, which can be attached to existing pipe structures. For this task a method is developed, which uses an ultrasonic clamp-on device. This method is based on the impact of such deposition layers on the propagation of circumferential guided waves on the pipe wall. Such waves are partly converted into longitudinal compressional waves in the liquid, which are back-converted to guided waves in a circular cross section of the pipe. Validating this approach, laboratory experiments with gelatin deposition layers on steel tubes exhibited a distinguishable sensitivity of both wave branches with respect to the thickness of such layers. This allows the monitoring of the layer growth.

On-chip analysis of respiratory viruses from nasopharyngeal samples.

Point-of-care (PoC) testing followed by personalized efficient therapy of infectious diseases may result in a considerable reduction of associated health care costs. Lab-on-a-chip (LoC) systems represent a potentially high efficient class of PoC tools. Here, we present a LoC system for automated pathogen analysis of respiratory viruses from nasopharyngeal specimens. The device prepares total nucleic acids from extracted swab samples using magnetic silica beads. After reverse transcription the co-purified viral RNA is amplified in accordance with the QIAplex multiplex PCR technology. Hybridized to corresponding QIAGEN LiquiChip beads and labelled with streptavidin R-phycoerythrin, the amplified target sequences are finally detected using a QIAGEN LiquiChip200 workstation. All chemicals needed are either stored freeze-dried on the disposable chip or are provided in liquid form in a reagent cartridge for up to 24 runs. Magnetic stir bars for mixing as well as turning valves with metering structures are integrated into the injection-moulded disposable chip. The core of the controlling instrument is a rotating heating bar construction providing fixed temperatures for fast cycling. PCR times of about half an hour (for 30 cycles) could be achieved for 120 µl reactions, making this system the fastest currently available high-volume PCR chip. The functionality of the system was shown by comparing automatically processed nasopharyngeal samples to ones processed manually according to the QIAGEN "ResPlex™ II Panel v2.0" respiratory virus detection kit. A prototype of the present instrument revealed slightly weaker signal intensities with a similar sensitivity in comparison to the commercially available kit and automated nucleic acid preparation devices, even without protocol optimization.

Three-component reactions with (S)-methyl pyroglutamate: an efficient way to diversely substituted asymmetric amidocyclohexenes.

Chiral N-dienyl lactams are crucial building blocks for the synthesis of complex organic compounds. However, their generation is rather challenging. This paper reports the novel one-pot reaction of (S)-methyl pyroglutamate as the amide component with different aldehydes and dienophiles (AAD reaction) to give novel chiral 1-amido-2-cyclohexenes. The corresponding N-dienyl lactams generated in situ undergo subsequent Diels-Alder reactions in good yield and diastereoselectivity. The scope and limitations of the three-component protocol were investigated. X-ray and NMR spectroscopic analysis of the products as well as DFT calculations of the intermediates were also performed to explain the observed stereoselectivity and structural features.

In situ generation of chiral N-dienyl lactams in a multicomponent reaction: an efficient and highly selective way to asymmetric amidocyclohexenes.

Chiral N-dienyl lactams are crucial building blocks for the synthesis of complex organic compounds. However, their generation is rather challenging. This paper reports on a highly efficient and diastereoselective multicomponent methodology utilizing chiral amides, aldehydes, and dienophiles (AAD reaction). The three components readily react under in situ generation of chiral N-dienyl lactams which undergo a subsequent Diels-Alder reaction. Different chiral amides have been employed in the standard protocol delivering yields up to 94%, and selectivities up to 90% de. Moreover, DFT calculations were performed to explain the obtained selectivities.

A new fast method for nanoLC-MALDI-TOF/TOF-MS analysis using monolithic columns for peptide preconcentration and separation in proteomic studies.

A new fast method for identification and characterization of proteolytic digests of proteins by monolithic liquid chromatography coupled with mass spectrometry has been developed. The advantages of the monolithic columns are a high-pressure stability and low back pressure resulting in higher flow rates for capillary or nanosize columns simplifying the system handling. As was shown in several publications, such monolithic stationary phases are highly qualified for the analysis of peptides and proteins, but so far, only small volumes could be injected into the system, which might hamper the sample preparation leading to protein precipitation and partial loss of sample. To overcome the problem of small injection volumes, we established a system including a short monolithic trap column to allow preconcentration of the peptides. The injected sample is flushed at higher flow rates onto the trap column, bound to the stationary phase, and in this way concentrated in a few nanoliters before starting the separation. The expanded system was optimized and tested using different reference protein samples. Eluting peptides were detected by MALDI-TOF/TOF-MS and identified by database searching. The system is now a permanent part for proteome analysis in our lab, and as such, it was successfully applied for the detection of post-translational modifications and the analysis of membrane proteins. One example for these analyses is also included in this paper.

Synthesis and antimicrobial activity of N-analogous corollosporines.

Corollosporine is an antimicrobial metabolite, which was isolated from the marine fungus Corollospora maritima. Owing to its basic 4-hydroxyphthalic acid anhydride structure, it has become an attractive target for a structure/activity relationship modelling of derived compounds with potential antibiotic activity. In this regard we report on the straightforward synthesis of hetero analogous corollosporines, which were easily prepared by a three-step reaction sequence, taking advantage of a novel multicomponent reaction (AAD-reaction) and a subsequent aromatization/Grignard reaction protocol. Furthermore, the obtained products were tested in several biological assays to evaluate their antimicrobial activity.

A novel MCR of isocyanates, aldehydes, and dienophiles.

[reaction: see text] A novel one-pot procedure for the three-component coupling reaction of isocyanates, aldehydes, and dienophiles (IAD reaction) has been developed. Condensation of isocyanates and aldehydes and subsequent Diels-Alder reactions with electron-deficient dienophiles furnishes endo-selective amino-substituted cyclohexenes in good yield.

Automated chip-based device for simple and fast nucleic acid amplification.

A chip-based PCR device is presented that is capable of rapid temperature ramping and handling sample volumes in the microliter range. The PCR chip comprises a microchannel thermally connected to three temperature zones. Inside this microchannel, the PCR sample plug is driven and precisely positioned by a ferrofluidic actuator for more than 40 cycles within 5 min. Computer simulations predict that the sample plugs are thermally equilibrated on a time scale of some 10 ms when transported to a different temperature zone. Hence, the thermal limitations on the cycle speed of the system are considerably reduced compared with conventional cyclers. The system was developed on a modular platform suitable for handling further microfluidic tasks such as DNA extraction and preparation of the PCR mix. Thus, the aspired chip-based platform represents not only a PCR system but a complete analysis system, from the injection of a patient's blood sample to its final appraisal.

Synthesis of enantiomerically pure cyclohex-2-en-1-ols: development of novel multicomponent reactions.

Multicomponent reactions of aldehydes, dienophiles, and alcohols or carboxylic acid anhydrides have been developed for the first time. In situ generation of 1-acyloxy- and 1-alkoxy-1,3-butadiene derivatives in toluene in the presence of electron-deficient dienophiles provides selective and efficient access to functionalized cyclohex-2-ene-1-ols in good yields. Subsequent enzyme-catalyzed kinetic resolution gave the corresponding enantiomers with high enantioselectivity.

Parallel nanoliter detection of cancer markers using polymer microchips.

A general multipurpose microchip technology platform for point-of-care diagnostics has been developed. Real-time nucleic acid sequence-based amplification (NASBA) for detection of artificial human papilloma virus (HPV) 16 sequences and SiHa cell line samples was successfully performed in cyclic olefin copolymer (COC) microchips, incorporating supply channels and parallel reaction channels. Samples were distributed into 10 parallel reaction channels, and signals were simultaneously detected in 80 nl volumes. With a custom-made optical detection unit, the system reached a sensitivity limit of 10(-6) microM for artificial HPV 16 sequences, and 20 cells microl(-1) for the SiHa cell line. This is comparable to the detection limit of conventional readers, and clinical testing of biological samples in polymer microchips using NASBA is therefore possible.