Bacteriophage-loaded functional nanofibers for treatment of P. aeruginosa and S. aureus wound infections.

The increasing incidence of infected skin wounds poses a major challenge in clinical practice, especially when conventional antibiotic therapy fails. In this context, bacteriophages emerged as promising alternatives for the treatment of antibiotic-resistant bacteria. However, clinical implementation remains hampered by the lack of efficient delivery approaches to infected wound tissue. In this study, bacteriophage-loaded electrospun fiber mats were successfully developed as next-generation wound dressings for the treatment of infected wounds. We employed a coaxial electrospinning approach, creating fibers with a protective polymer shell, enveloping bacteriophages in the core while maintaining their antimicrobial activity. The novel fibers exhibited a reproducible fiber diameter range and morphology, while the mechanical fiber properties were ideal for application onto wounds. Further, immediate release kinetics for the phages were confirmed as well as the biocompatibility of the fibers with human skin cells. Antimicrobial activity was demonstrated against Staphylococcus aureus and Pseudomonas aeruginosa and the core/shell formulation maintained the bacteriophage activity for 4 weeks when stored at - 20 °C. Based on these promising characteristics, our approach holds great potential as a platform technology for the encapsulation of bioactive bacteriophages to enable the translation of phage therapy into clinical application.

Electrospun Scaffolds as Cell Culture Substrates for the Cultivation of an In Vitro Blood-Brain Barrier Model Using Human Induced Pluripotent Stem Cells.

The human blood-brain barrier (BBB) represents the interface of microvasculature and the central nervous system, regulating the transport of nutrients and protecting the brain from external threats. To gain a deeper understanding of (patho)physiological processes affecting the BBB, sophisticated models mimicking the in vivo situation are required. Currently, most in vitro models are cultivated on stiff, semipermeable, and non-biodegradable Transwell® membrane inserts, not adequately mimicking the complexity of the extracellular environment of the native human BBB. To overcome these disadvantages, we developed three-dimensional electrospun scaffolds resembling the natural structure of the human extracellular matrix. The polymer fibers of the scaffold imitate collagen fibrils of the human basement membrane, exhibiting excellent wettability and biomechanical properties, thus facilitating cell adhesion, proliferation, and migration. Cultivation of human induced pluripotent stem cells (hiPSCs) on these scaffolds enabled the development of a physiological BBB phenotype monitored via the formation of tight junctions and validated by the paracellular permeability of sodium fluorescein, further accentuating the non-linearity of TEER and barrier permeability. The novel in vitro model of the BBB forms a tight endothelial barrier, offering a platform to study barrier functions in a (patho)physiologically relevant context.

End-to-end topology for fiber comb based optical frequency transfer at the 10-21 level: erratum.

In this erratum we correct errors in the scaling and caption of Fig. 4 in the original manuscript [1].

Comb-locked frequency-swept synthesizer for high precision broadband spectroscopy.

Frequency combs have made optical metrology accessible to hundreds of laboratories worldwide and they have set new benchmarks in multi-species trace gas sensing for environmental, industrial and medical applications. However, current comb spectrometers privilege either frequency precision and sensitivity through interposition of a cw probe laser with limited tuning range, or spectral coverage and measurement time using the comb itself as an ultra-broadband probe. We overcome this restriction by introducing a comb-locked frequency-swept optical synthesizer that allows a continuous-wave laser to be swept in seconds over spectral ranges of several terahertz while remaining phase locked to an underlying frequency comb. This offers a unique degree of versatility, as the synthesizer can be either repeatedly scanned over a single absorption line to achieve ultimate precision and sensitivity, or swept in seconds over an entire rovibrational band to capture multiple species. The spectrometer enables us to determine line center frequencies with an absolute uncertainty of 30 kHz and at the same time to collect absorption spectra over more than 3 THz with state-of-the-art sensitivity of a few 10-10 cm-1. Beyond precision broadband spectroscopy, the proposed synthesizer is an extremely promising tool to force a breakthrough in terahertz metrology and coherent laser ranging.

End-to-end topology for fiber comb based optical frequency transfer at the 10-21 level.

We introduce a simple and robust scheme for optical frequency transfer of an ultra-stable source light field via an optical frequency comb to a field at a target optical frequency, where highest stability is required, e.g., for the interrogation of an optical clock. The scheme relies on a topology for end-to-end suppression of the influence of optical path-length fluctuations, which is attained by actively phase-stabilized delivery, combined with common-path propagation. This approach provides a robust stability improvement without the need for additional isolation against environmental disturbances such as temperature, pressure or humidity changes. We measure residual frequency transfer instabilities by comparing the frequency transfers carried out with two independent combs simultaneously. Residual fractional frequency instabilities between two systems of 8 × 10-18 at 1 s and 3 × 10-21 at 105 s averaging time are observed. We discuss the individual noise contributions to the residual instability. The presented scheme is technically simple, robust against environmental parameter fluctuations and enables an ultra-stable frequency transfer, e.g., to optical clock lasers or to lasers in gravitational wave detectors.

Phase-predictable tuning of single-frequency optical synthesizers.

We investigate the tuning behavior of a novel type of single-frequency optical synthesizers by phase comparison of the output signals of two identical devices. We achieve phase-stable and cycle-slip free frequency tuning over 28.1 GHz with a maximum zero-to-peak phase deviation of 62 mrad. In contrast to previous implementations of single-frequency optical synthesizers, no comb line order switching is needed when tuned over more than one comb line spacing range of the employed frequency comb.

Endless frequency shifting of optical frequency comb lines.

The functional principle of a novel technique for frequency shifting lines of an optical frequency comb is demonstrated. The underlying principle is to shift the carrier frequency by changing the carrier phase within the time span between subsequent pulses of a mode-locked laser used as comb generator. This universal frequency shifter does not require intrusion into the comb generator and provides high agility for arbitrary temporal frequency evolutions.

High contrast, low noise selection and amplification of an individual optical frequency comb line.

We present a frequency-selective amplifier for optical frequency combs based on stimulated Brillouin scattering and the effect of a Brillouin dynamic grating. A user defined individual frequency comb line is amplified while the other comb lines are efficiently suppressed, rendering a frequency-stable clean-up oscillator unnecessary. A measured signal to noise ratio of 89 dBc/Hz proves the suitability of the method for phase coherent measurements. The overall noise figure is 6 dB.

Robust interferometric frequency lock between cw lasers and optical frequency combs.

A transfer interferometer is presented which establishes a versatile and robust optical frequency locking link between a tunable single frequency laser and an optical frequency comb. It enables agile and continuous tuning of the frequency difference between both lasers while fluctuations and drift effects of the transfer interferometer itself are widely eliminated via common mode rejection. Experimental results will be presented for a tunable extended-cavity 1.5 µm laser diode locked to an Er-fiber based frequency comb.

Submicron positioning of single atoms in a microcavity.

The coupling of individual atoms to a high-finesse optical cavity is precisely controlled and adjusted using a standing-wave dipole-force trap, a challenge for strong atom-cavity coupling. Ultracold Rubidium atoms are first loaded into potential minima of the dipole trap in the center of the cavity. Then we use the trap as a conveyor belt that we set into motion perpendicular to the cavity axis. This allows us to repetitively move atoms out of and back into the cavity mode with a repositioning precision of 135 nm. This makes it possible to either selectively address one atom of a string of atoms by the cavity, or to simultaneously couple two precisely separated atoms to a higher mode of the cavity.