Piezoelectric titanium based microfluidic pump and valves for implantable medical applications

Medical devices often require precise movement of fluids. Automated implants with no need for manual handling improve patient care significantly. However, existing microfluidic devices do not fulfil the necessary specifications of size, safety, hermetic sealing, and artefact free medical imaging, as well as energy efficiency combined with adapted fluidic properties. In this work we designed, manufactured, and experimentally evaluated three piezoelectric microfluidic devices for implant automation: a diaphragm pump, a normally closed valve, and a normally open valve. All devices are made of titanium, minimizing the risk of artefacts in medical imaging. They have similar form factors and use the same actuation method. For the later, a specific mounting process of the piezo actuator enables outstanding fluidic performance during experimental evaluations. The titanium micropumps show a maximal flow of (14 ± 2.2) ml/min and pressure build-up of 75 kPa. The normally closed valve’s leakage rates are extremely low with less than 1 μL/min. Detailed investigations further include the actuator stroke, a lifetime study for normally open valves, and a numerical and experimental evaluation of the normally closed valve’s spring foil. The introduced titanium technology platform is ideally suited for system integration accounted for by the use of the same actuation principle and the similar form factor and a simple design. The development of small, smart, and energy efficient implants for improved treatment is possible based on the introduced platform

Transient Retention of Photoreceptor Outer Segments in Matrigel-Embedded Retinal Organoids

Retinal organoids (ROs) are three-dimensional retinal tissues, which are differentiated in vitro from induced pluripotent stem cells (iPSC), ultimately forming all main retinal cell types under defined culture conditions. ROs show several highly specialized retinal features, including the outgrowth of photoreceptor outer segments (OSs). In vivo, the photoreceptor OSs are enveloped and maintained by protrusions of retinal pigment epithelium (RPE) cells, the so-called apical microvilli, while ROs fail to recapitulate this critical interaction in culture development. Here, we define specific co-culture conditions aiming to compensate for the missing physical proximity of RPE and OSs in RO development. Accordingly, functional RPE cells and ROs were differentiated simultaneously from the same iPSC clone, the former resulting in byproduct RPE or bRPE cells. While some co-culture approaches indicated a temporary functional interaction between bRPE and RO photoreceptors, they did not improve the photoreceptor histoarchitecture. In contrast, embedding ROs in a basement membrane extract without bRPE cells showed a robust improvement in the rate of photoreceptor OS retention. RO embedding is a quick and easy method that greatly enhances the preservation of photoreceptor OSs, an important structure for modelling retinal diseases with the involvement of photoreceptors

Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

Radiofrequency Electromagnetic Fields Cause Non-Temperature-Induced Physical and Biological Effects in Cancer Cells

Non-temperature-induced effects of radiofrequency electromagnetic fields (RF) have been controversial for decades. Here, we established measurement techniques to prove their existence by investigating energy deposition in tumor cells under RF exposure and upon adding amplitude modulation (AM) (AMRF). Using a preclinical device LabEHY-200 with a novel in vitro applicator, we analyzed the power deposition and system parameters for five human colorectal cancer cell lines and measured the apoptosis rates in vitro and tumor growth inhibition in vivo in comparison to water bath heating. We showed enhanced anticancer effects of RF and AMRF in vitro and in vivo and verified the non-temperature-induced origin of the effects. Furthermore, apoptotic enhancement by AM was correlated with cell membrane stiffness. Our findings not only provide a strategy to significantly enhance non-temperature-induced anticancer cell effects in vitro and in vivo but also provide a perspective for a potentially more effective tumor therapy

Generation and Characterization of Rat and Mouse Monoclonal Antibodies Specific for MeCP2 and Their Use in X-Inactivation Studies

Methyl CpG binding protein 2 (MeCP2) binds DNA, and has a preference for methylated CpGs and, hence, in cells, it accumulates in heterochromatin. Even though it is expressed ubiquitously MeCP2 is particularly important during neuronal maturation. This is underscored by the fact that in Rett syndrome, a neurological disease, 80% of patients carry a mutation in the MECP2 gene. Since the MECP2 gene lies on the X chromosome and is subjected to X chromosome inactivation, affected patients are usually chimeric for wild type and mutant MeCP2. Here, we present the generation and characterization of the first rat monoclonal MeCP2 specific antibodies as well as mouse monoclonal antibodies and a rabbit polyclonal antibody. We demonstrate that our antibodies are suitable for immunoblotting, (chromatin) immunoprecipitation and immunofluorescence of endogenous and ectopically expressed MeCP2. Epitope mapping revealed that most of the MeCP2 monoclonal antibodies recognize the C-terminal domain and one the N-terminal domain of MeCP2. Using slot blot analysis, we determined a high sensitivity of all antibodies, detecting amounts as low as 1 ng of MeCP2 protein. Moreover, the antibodies recognize MeCP2 from different species, including human, mouse, rat and pig. Lastly, we have validated their use by analyzing and quantifying X chromosome inactivation skewing using brain tissue of MeCP2 heterozygous null female mice. The new MeCP2 specific monoclonal antibodies described here perform well in a large variety of immunological applications making them a very valuable set of tools for studies of MeCP2 pathophysiology in situ and in vitro

Radiofrequency Electromagnetic Fields Cause Non-Temperature-Induced Physical and Biological Effects in Cancer Cells

Non-temperature-induced effects of radiofrequency electromagnetic fields (RF) have been controversial for decades. Here, we established measurement techniques to prove their existence by investigating energy deposition in tumor cells under RF exposure and upon adding amplitude modulation (AM) (AMRF). Using a preclinical device LabEHY-200 with a novel in vitro applicator, we analyzed the power deposition and system parameters for five human colorectal cancer cell lines and measured the apoptosis rates in vitro and tumor growth inhibition in vivo in comparison to water bath heating. We showed enhanced anticancer effects of RF and AMRF in vitro and in vivo and verified the non-temperature-induced origin of the effects. Furthermore, apoptotic enhancement by AM was correlated with cell membrane stiffness. Our findings not only provide a strategy to significantly enhance non-temperature-induced anticancer cell effects in vitro and in vivo but also provide a perspective for a potentially more effective tumor therapy

SCIAMACHY: The new Level 0-1 Processor

SCIAMACHY (SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY) is a scanning nadir and limb spectrometer covering the wavelength range from 212 nm to 2386 nm in 8 channels. It is a joint project of Germany, the Netherlands and Belgium and was launched in February 2002 on the ENVISAT platform. After the platform failure in April 2012, SCIAMACHY is now in the postprocessing phase F. SCIAMACHY�s originally specified in-orbit lifetime was double the planned lifetime. SCIAMACHY was designed to measure column densities and vertical profiles of trace gas species in the mesosphere, in the stratosphere and in the troposphere (Bovensmann et al., 1999). It can detect a large amount of atmospheric gases (e.g. O3 , H2CO, CHOCHO, SO2 , BrO, OClO, NO2 , H2O, CO, CH4 , among others ) and can provide information about aerosols and clouds. The operational processing of SCIAMACHY is split into Level 0-1 processing (essentially providing calibrated radiances) and Level 1-2 processing providing geophysical products. The operational Level 0-1 processor has been completely re-coded and embedded in a newly developed framework that speeds up processing considerably. In the frame of the SCIAMACHY Quality Working Group activities, ESA is continuing the improvement of the archived data sets. Currently Version 9 of the Level 0-1 processor is being implemented. It will include An updated degradation correction Several improvements in the SWIR spectral range like a better dark correction, an improved dead & bad pixel characterisation and an improved spectral calibration Improvements to the polarisation correction algorithm Improvements to the geolocation by a better pointing characterisation Additionally a new format for the Level 1b and Level 1c will be implemented. The version 9 products will be available in netCDF version 4 that is aligned with the formats of the GOME -1 and Sentinel missions. We will present the first results of the new Level 0-1 processing in this paper

Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives

The increased utilization of metrology resources and expanded application of its’ approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects

Stratospheric CH4 and CO2 profiles derived from SCIAMACHY solar occultation measurements

Stratospheric profiles of methane (CH$_{4}$) and carbon dioxide (CO$_{2}$) have been derived from solar occultation measurements of the SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY). The retrieval is performed using a method called onion peeling DOAS (ONPD), which combines an onion peeling approach with a weighting function DOAS (differential optical absorption spectroscopy) fit in the spectral region between 1559 and 1671 nm. By use of updated pointing information and optimisation of the data selection as well as of the retrieval approach, the altitude range for reasonable CH$_{4}$ could be broadened from 20 to 40 km to about 17 to 45 km. Furthermore, the quality of the derived CO$_{2}$ has been assessed such that now the first stratospheric profiles (17–45 km) of CO$_{2}$ from SCIAMACHY are available. Comparisons with independent data sets yield an estimated accuracy of the new SCIAMACHY stratospheric profiles of about 5–10% for CH$_{4}$ and 2–3% for CO$_{2}$. The accuracy of the products is currently mainly restricted by the appearance of unexpected vertical oscillations in the derived profiles which need further investigation. Using the improved ONPD retrieval, CH$_{4}$ and CO$_{2}$ stratospheric data sets covering the whole SCIAMACHY time series (August 2002–April 2012) and the latitudinal range between about 50 and 70° N have been derived. Based on these time series, CH$_{4}$ and CO$_{2}$ 2 trends have been estimated. CH$_{4}$ trends above about 20 km are not significantly different from zero and the trend at 17 km is about 3 ppbvyear$^{-1}$. The derived CO$_{2}$ trends show a general decrease with altitude with values of about 1.9 ppmvyear$^{-1}$ at 21 km and about 1.3 ppmvyear$^{-1}$ at 39 km. These results are in reasonable agreement with total column trends for these gases. This shows that the new SCIAMACHY data sets can provide valuable information about the stratosphere