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We show new approaches to developing acoustic liquid sensors based on phononic crystals. The proposed phononic crystal integrates fluidic elements. A solid block with periodic cylindrical holes contains a defect—a liquid-filled cylindrical cavity. We pay attention to acoustic excitation and the readout of the axisymmetric cylindrical resonator eigenmode of the liquid-filled defect in the middle of the phononic crystal structure. This mode solves the challenge of mechanical energy losses due to liquid viscosity. We also analyze the coupling effects between oscillations of liquid and solid systems and consider coupling issues between piezoelectric transducers and the liquid-filled cavity resonator. The numerical simulation of the propagation of acoustic waves through the phononic crystal sensor was carried out in COMSOL Multiphysics Software. The phononic crystal was made of stainless steel with mechanically drilled holes and was fabricated for experimental verification. We show that a tuning of the solid–liquid vibrational modes coupling is the key to an enhanced level of sensitivity to liquid properties. Besides (homogeneous) water–propanol mixtures, experimental studies were carried out on (disperse) water–fuel emulsions. [ABSTRACT FROM AUTHOR]

Abstract Background A critical point during the course of central nervous system infection is the influx of leukocytes from the blood into the brain across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). However, experimental in vitro models to investigate leukocyte transmigration across cultured choroid plexus epithelial cells have been lacking so far. Methods We have developed a porcine and human “inverted” culture insert system that enables leukocyte transmigration specifically from the physiologically relevant basolateral side. The models use primary porcine choroid plexus epithelial cells (PCPEC) and human choroid plexus papilloma cells (HIBCPP). As a prerequisite for a functional barrier, we optimized culture conditions in which cells are maintained in serum-containing medium until high barrier function is reached. Leukocyte transmigration through the plexus epithelial cells is analysed by three-dimensional Apotome®-imaging and electron microscopy, and the route of transmigration through the plexus epithelial cells, i.e. transcellular as well as paracellular, can be determined. Discussion As a functionally relevant porcine and human BCSFB model, PCPEC and HIBCPP respectively, offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens. Moreover, our in vitro models facilitate the investigation of leukocyte entry into the CNS via the blood-CSF barrier.

Milk is a product that requires quality control at all stages of production: from the dairy farm, processing at the dairy plant to finished products. Milk is a complex multiphase polydisperse system, whose components not only determine the quality and price of raw milk, but also reflect the physiological state of the herd. Today's production volumes and rates require simple, fast, cost-effective, and accurate analytical methods, and most manufacturers want to move away from methods that use reagents that increase analysis time and move to rapid analysis methods. The review presents methods for the rapid determination of the main components of milk, examines their advantages and disadvantages. Optical spectroscopy is a fast, non-destructive, precise, and reliable tool for determination of the main constituents and common adulterants in milk. While mid-infrared spectroscopy is a well-established off-line laboratory technique for the routine quality control of milk, near-infrared technologies provide relatively low-cost and robust solutions suitable for on-site and in-line applications on milking farms and dairy production facilities. Other techniques, discussed in this review, including Raman spectroscopy, atomic spectroscopy, molecular fluorescence spectroscopy, are also used for milk analysis but much less extensively. Acoustic methods are also suitable for non-destructive on-line analysis of milk. Acoustic characterization can provide information on fat content, particle size distribution of fat and proteins, changes in the biophysical properties of milk over time, the content of specific proteins and pollutants. The basic principles of ultrasonic techniques, including transmission, pulse-echo, interferometer, and microbalance approaches, are briefly described and milk parameters measured with their help, including frequency ranges and measurement accuracy, are given. [ABSTRACT FROM AUTHOR]

Die Implementierung von Biosensoren in mikrofluidische Strukturen für Organ-on-a-Chip-Anwendungen ist eine vielversprechende Forschungsrichtung. Es kann Messungen der biologischen Reaktion in unmittelbarer Nähe von kultivierten In-vitro-Zellen ermöglichen. Ein zu messender Schlüsselparameter ist die Ionenkonzentration. Daher stellen wir in dieser Arbeit das Design, die Herstellung und die erste Testung eines Biosensors auf Basis eines organischen elektrochemischen Transistors (OECT) vor, der in einen Mikrofluidikkanal implementiert ist. Zur Herstellung der Elektroden und der aktiven Schicht für OECT wurden nur organische Polymere verwendet. In ersten Messungen konnte eine sehr gute Korrelation zwischen dem gemessenen und berechneten UI-Diagramm des Transistors gezeigt werden. Es wurden Messungenauigkeiten im Zusammenhang mit der Streuung von Materialeigenschaften und Fertigungstoleranzen analysiert und die Ungenauigkeit der Drainstrommessung ermittelt. Implementation of biosensors into microfluidic structures for organ-on-a-chip applications is an emerging promising research direction. It may enable measurements of the biological response in the direct vicinity of cultured in-vitro cells. One key parameter to be measured is ionic concentration. Therefore, in this work we present design, manufacturing and initial testing of an organic electrochemical transistor (OECT) based biosensor implemented into a microfluidic channel. Only organic polymers were utilized for realizing the electrodes and the active layer for OECT. There is an excellent correlation between measured and calculated VI characteristics of the transistor. We analyze measurement inaccuracies, related to spread of material properties and manufacturing tolerances. We derive analytic expressions for drain current measurement inaccuracy. [ABSTRACT FROM AUTHOR]

Die Umkehrbarkeit elastischer Wellen in linearen Systemen kann ausgenutzt werden, um zeitlich und lokal begrenzte Vibrationsereignisse auf Oberflächen zu erzeugen. Das damit verbundene Verfahren der Zeitumkehr findet bereits in anderen Bereichen der Medizintechnik, Werkstoffprüfung oder Lokalisierung von Fingerberührungen auf Oberflächen erfolgreichen Einsatz. Aufgrund der mit elastischen Wellen hervorgerufenen Oberflächenauslenkung bietet sich weiterführend die Möglichkeit, auf berührungssensitiven Bildschirmen dem Nutzer eine lokal begrenzte haptische Rückmeldung zu geben, um so beispielsweise auch für visuell beeinträchtigte Personen die Verwendbarkeit von Touch-Displays im täglichen Umfeld zu gewährleisten. Die Veröffentlichung demonstriert in diesem Kontext eine simulationsgestützte Studie zur Realisierung lokaler haptisch erfassbarer Vibrationsbereiche. The reversibility of an elastic wave can be used to refocus a signal on a local spot by time reversal (TR) techniques. Numerous application fields are connected to this technology, such as medical intervention, non-destructive testing or impact localization on touchscreen systems. However, since there is no haptic feedback, touchscreens require the users to visually control their interaction. This limits the usability in cases of individual physical constraints or environmental conditions. The contribution addresses a technique that uses elastic waves to realize a local vibro-tactile sensation on the screen, supported by simulation-based studies. [ABSTRACT FROM AUTHOR]

Die Methode der Signalanalyse für nicht-invasive Ultraschallsysteme auf Basis der linearen Modellierung und der mathematischen Optimierung wird erläutert. The signal processing in case of non-invasive ultrasonic applications is discussed in the paper. This adresses signal oriented modelling of linear systems for parameter estimation in layered media. [ABSTRACT FROM AUTHOR]

Background: Bacterial invasion through the blood-cerebrospinal fluid barrier (BCSFB) during bacterial meningitis causes secretion of proinflammatory cytokines/chemokines followed by the recruitment of leukocytes into the CNS. In this study, we analyzed the cellular and molecular mechanisms of polymorphonuclear neutrophil (PMN) and monocyte transepithelial transmigration (TM) across the BCSFB after bacterial infection. Methods: Using an inverted transwell filter system of human choroid plexus papilloma cells (HIBCPP), we studied leukocyte TM rates, the migration route by immunofluorescence, transmission electron microscopy and focused ion beam/scanning electron microscopy, the secretion of cytokines/chemokines by cytokine bead array and posttranslational modification of the signal regulatory protein (SIRP) a via western blot. Results: PMNs showed a significantly increased TM across HIBCPP after infection with wild-type Neisseria meningitidis (MC58). In contrast, a significantly decreased monocyte transmigration rate after bacterial infection of HIBCPP could be observed. Interestingly, in co-culture experiments with PMNs and monocytes, TM of monocytes was significantly enhanced. Analysis of paracellular permeability and transepithelial electrical resistance confirmed an intact barrier function during leukocyte TM. With the help of the different imaging techniques we could provide evidence for para- as well as for transcellular migrating leukocytes. Further analysis of secreted cytokines/ chemokines showed a distinct pattern after stimulation and transmigration of PMNs and monocytes. Moreover, the transmembrane glycoprotein SIRPa was deglycosylated in monocytes, but not in PMNs, after bacterial infection. Conclusions: Our findings demonstrate that PMNs and monoctyes differentially migrate in a human BCSFB model after bacterial infection. Cytokines and chemokines as well as transmembrane proteins such as SIRPα may be involved in this process. [ABSTRACT FROM AUTHOR]

Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip devices are gaining popularity in medical research due to the possibility of performing extremely complex living-body-resembling research in vitro. For this reason, there is a substantial drive in developing technologies capable of producing such structures in a simple and, at the same time, flexible manner. One of the primary challenges in producing organ-on-chip devices from a manufacturing standpoint is the prevalence of layer-by-layer bonding techniques, which result in limitations relating to the applicable materials and geometries and limited repeatability. In this work, we present an improved approach, using three dimensional (3D) laser lithography for the direct integration of a functional part—the membrane—into a closed-channel system. We show that it allows the freely choice of the geometry of the membrane and its integration into a complete organ-on-a-chip system. Considerations relating to sample preparation, the writing process, and the final preparation for operation are given. Overall, we consider that the broader application of 3D laser lithography in organ-on-a-chip fabrication is the next logical step in this field's evolution. [ABSTRACT FROM AUTHOR]

Periodic elastic composite structures attract great attention. They offer the ability to design artificial properties to advance the control over the propagation of elastic/acoustic waves. In previous work, we drew attention to composite periodic structures comprising liquids. It was shown that the transmission spectrum of the structure, specifically a well-isolated peak, follows the material properties of liquid constituent in a distinct manner. This idea was realized in several liquid sensor concepts that launched the field of phononic crystal liquid sensors. In this work we introduce a novel concept—narrow band solid-liquid composite arrangements. We demonstrate two different concepts to design narrow band structures, and show the results of theoretical studies and results of experimental investigations that confirm the theoretical predictions. This work extends prior studies in the field of phononic crystal liquid sensors with novel concepts and results that have a high potential in a field of volumetric liquid properties evaluation. [ABSTRACT FROM AUTHOR]

An acoustic reflection measurement technique is presented, which detects and evaluates the ultrasonic waves backscattered at the particles within a liquid dispersion. The technique is based on an iterative pulse-echo method, which gathers a sufficiently high number of single reflection signals and eventually conducts a statistical analysis yielding two principal parameters of the backscattering signal: its maximum amplitude and its time-dependent decay. Theoretical considerations and experimental investigations show that maximum amplitude of the backscattering signal correlates with the averaged backscattering coefficient of the particles and that the decay rate of the backscattering signal can be attributed to sound attenuation, even though the impact of multiple scattering (i.e. non-linear concentration effects) is much more pronounced as for a transmission setup. Since the developed measurement technique is specifically designed for the in-situ characterisation of concentrated dispersion, it is necessary to adequately account for multiple scattering effects when evaluating the backscattering data. For this purpose a semi-empirical model is developed, which combines an established single particle scattering model with predictions of wave interference for defined microstructure of the dispersion. Experiments on two different types of dispersion confirm the applicability of this approach for concentrations up to 30 vol.%. The experimental results additionally show that the maximum backscattering amplitude is highly sensitive to particle size, whereas the decay rate particularly reflects the impact of particle concentration. Finally a scheme is proposed, which allows for calculating the mean particle size and the volume fraction of the dispersed phase. [ABSTRACT FROM AUTHOR]

Background: The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens., Methods: Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria., Results: We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection., Conclusions: Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6 signaling and the transcriptional regulator IκBζ.