Optical cavity reaching 10-16 frequency stability with compact optical circulator based in-coupling optics.

Future space missions will benefit from highly stable and compact optical frequency references. While many promising technologies are currently under investigation, optical cavities are a well-suited technique for applications in which relative references are required. To improve the frequency stability of optical cavities, a key step in combining high performance with compactness and robustness is the further development of in-coupling optics. Here, we present our work of using a fiber-coupled circulator based in-coupling for a high-finesse optical cavity. Implementing the new, to the best of our knowledge, in-coupling board to an extensively characterized crossed cavity set-up allows us to identify possible differences to the commonly used free-beam technique. With a frequency stability of 5.5×10-16 H z -1/2 at 1 Hz and with only a slight degradation in frequency stability below the mHz range, no circulator-caused instabilities were observed.

Choice of the Miniature Inertial Optomechanical Sensor Geometric Parameters with the Help of Their Mechanical Characteristics Modelling.

In this paper, the mechanical characteristics of a miniature optomechanical accelerometer, similar to those proposed for a wide range of applications, have been investigated. With the help of numerical modelling, characteristics such as eigenfrequencies, quality factor, displacement magnitude, normalized translations, normalized rotations versus eigenfrequencies, as well as spatial distributions of the azimuthal and axial displacements and stored energy density in a wide frequency range starting from the stationary case have been obtained. Dependencies of the main mechanical characteristics versus the minimal and maximal system dimensions have been plotted. Geometries of the optomechanical accelerometers with micron size parts providing the low and the high first eigenfrequencies are presented. It is shown that via the choice of the geometrical parameters, the minimal measured acceleration level can be raised substantially.

Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system.

Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional human multi-organ systems containing iPSC derived cardiomyocytes and primary hepatocytes were maintained under flow using a low-volume pumpless system in a serum-free medium. The functional readouts for contractile force and electrical conductivity enabled the non-invasive study of cardiac function. The presence of the hepatocytes in the system induced cardiotoxic effects from cyclophosphamide and reduced them for terfenadine due to drug metabolism, as expected from each compound's pharmacology. A computational fluid dynamics simulation enabled the prediction of terfenadine-fexofenadine pharmacokinetics, which was validated by HPLC-MS. This in vitro platform recapitulates primary aspects of the in vivo crosstalk between heart and liver and enables pharmacological studies, involving both organs in a single in vitro platform. The system enables non-invasive readouts of cardiotoxicity of drugs and their metabolites. Hepatotoxicity can also be evaluated by biomarker analysis and change in metabolic function. Integration of metabolic function in toxicology models can improve adverse effects prediction in preclinical studies and this system could also be used for chronic studies as well.

Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.

There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units. A system was developed in which human myotubes and motoneurons derived from stem cells were cultured in a serum-free medium in a BioMEMS construct. The system is composed of two chambers linked by microtunnels to enable axonal outgrowth to the muscle chamber that allows separate stimulation of each component and physiological NMJ function and MN stimulated tetanus. The muscle's contractions, induced by motoneuron activation or direct electrical stimulation, were monitored by image subtraction video recording for both frequency and amplitude. Bungarotoxin, BOTOX® and curare dose response curves were generated to demonstrate pharmacological relevance of the phenotypic screening device. This quantifiable functional hNMJ system establishes a platform for generating patient-specific NMJ models by including patient-derived iPSCs.