Benzo-Crown-Ether functionalized O-BODIPY Probes for Cations - A Selective Fluorescent Probe for Ba2.

Herein, we report the synthesis and sensing characteristics of 4,4'-methoxy-substituted BODIPY fluorescent probes (OBODIPYs) 3, 4 and 5 equipped with differently sized benzo-crown ethers (cf. Scheme 1, 3 (benzo-15-crown-5), 4 (benzo-18-crown-6) and 5 (benzo-21-crown7)). O-BODIPYs 3, 4 and 5 exhibited in comparison to their known F-BODIPY analogues 3a, 4a and 5a (cf. Scheme 1) an improved solubility in aqueous medium and higher fluorescence quantum yields. Fluorometric study in aqueous solutions of 3, 4 and 5 in the presence of different cations show cation induced fluorescence enhancements (FE). Compared to the benzo-crown ether substituted F-BODIPY analogues 3a, 4a and 5a, we found for the free O-BODIPYs 3, 4 and 5 higher fluorescence quantum yields (ϕf ) but lower cation induced FEs. We show that in aqueous medium the fluorescence quenching process (OFF switching), a photoinduced electron transfer, in O-BODIPYs 3, 4 and 5 is less effective and consequently sensitive and selective ON switching of the fluorescence by cations, too. Albeit these observations the novel benzo-21-crown-7 equipped fluorescent probe 5 exhibits a good fluorometric Ba2+ selectivity and Ba2+ sensitivity in conjunction to their superior aqueous solubility.

Selective and pH-Independent Detection of Ba2+ in Water by a Benzo-21-crown-7-Functionalized BODIPY.

Herein, we report on highly Ba2+ selective fluorescence sensing in water by a fluorescent probe consisting of a benzo-21-crown-7 as a Ba2+ binding unit (ionophore) and a tetramethylated BODIPY fluorophore as a fluorescence reporter. This fluorescent probe showed a Ba2+ induced fluorescence enhancement (FE) by a factor of 12±1 independently of the pH value and a high Ba2+ sensitivity with a limit of detection (LOD) of (17.2±0.3) µM. Moreover, a second fluorescent probe consisting of the same BODIPY fluorophore, but a benzo-18-crown-6 as a cation-responsive binding moiety, showed an even higher FE upon Ba2+ complexation by a factor of 85±3 and a lower LOD of (13±3) µM albeit a lower Ba2+ selectivity. The fluorescence sensing mechanism of Ba2+ was further investigated by time-resolved fluorescence as well as transient absorption spectroscopy (TAS) and it turned out that within these probes a blocking of a photoinduced electron transfer (PET) by Ba2+ is very likely responsible for the FE.

Single-Element Dual-Interferometer for Precision Inertial Sensing.

Tracking moving masses in several degrees of freedom with high precision and large dynamic range is a central aspect in many current and future gravitational physics experiments. Laser interferometers have been established as one of the tools of choice for such measurement schemes. Using sinusoidal phase modulation homodyne interferometry allows a drastic reduction of the complexity of the optical setup, a key limitation of multi-channel interferometry. By shifting the complexity of the setup to the signal processing stage, these methods enable devices with a size and weight not feasible using conventional techniques. In this paper we present the design of a novel sensor topology based on deep frequency modulation interferometry: the self-referenced single-element dual-interferometer (SEDI) inertial sensor, which takes simplification one step further by accommodating two interferometers in one optic. Using a combination of computer models and analytical methods we show that an inertial sensor with sub-picometer precision for frequencies above 10 mHz, in a package of a few cubic inches, seems feasible with our approach. Moreover we show that by combining two of these devices it is possible to reach sub-picometer precision down to 2 mHz. In combination with the given compactness, this makes the SEDI sensor a promising approach for applications in high precision inertial sensing for both next-generation space-based gravity missions employing drag-free control, and ground-based experiments employing inertial isolation systems with optical readout.

Na+ Selective Fluorescent Tools Based on Fluorescence Intensity Enhancements, Lifetime Changes, and on a Ratiometric Response.

Over the years, we developed highly selective fluorescent probes for K+ in water, which show K+ -induced fluorescence intensity enhancements, lifetime changes, or a ratiometric behavior at two emission wavelengths (cf. Scheme 1, K1-K4). In this paper, we introduce selective fluorescent probes for Na+ in water, which also show Na+ induced signal changes, which are analyzed by diverse fluorescence techniques. Initially, we synthesized the fluorescent probes 2, 4, 5, 6 and 10 for a fluorescence analysis by intensity enhancements at one wavelength by varying the Na+ responsive ionophore unit and the fluorophore moiety to adjust different Kd values for an intra- or extracellular Na+ analysis. Thus, we found that 2, 4 and 5 are Na+ selective fluorescent tools, which are able to measure physiologically important Na+ levels at wavelengths higher than 500 nm. Secondly, we developed the fluorescent probes 7 and 8 to analyze precise Na+ levels by fluorescence lifetime changes. Herein, only 8 (Kd =106 mm) is a capable fluorescent tool to measure Na+ levels in blood samples by lifetime changes. Finally, the fluorescent probe 9 was designed to show a Na+ induced ratiometric fluorescence behavior at two emission wavelengths. As desired, 9 (Kd =78 mm) showed a ratiometric fluorescence response towards Na+ ions and is a suitable tool to measure physiologically relevant Na+ levels by the intensity change of two emission wavelengths at 404 nm and 492 nm.

Picometer-Stable Hexagonal Optical Bench to Verify LISA Phase Extraction Linearity and Precision.

The Laser Interferometer Space Antenna (LISA) and its metrology chain have to fulfill stringent performance requirements to enable the space-based detection of gravitational waves. This implies the necessity of performance verification methods. In particular, the extraction of the interferometric phase, implemented by a phasemeter, needs to be probed for linearity and phase noise contributions. This Letter reports on a hexagonal quasimonolithic optical bench implementing a three-signal test for this purpose. Its characterization as sufficiently stable down to picometer levels is presented as well as its usage for a benchmark phasemeter performance measurement under LISA conditions. These results make it a candidate for the core of a LISA metrology verification facility.

A Ratiometric Fluorescent Probe for K+ in Water Based on a Phenylaza-18-Crown-6 Lariat Ether.

This work presents two molecular fluorescent probes 1 and 2 for the selective determination of physiologically relevant K+ levels in water based on a highly K+ /Na+ selective building block, the o-(2-methoxyethoxy)phenylaza-18-crown-6 lariat ether unit. Fluorescent probe 1 showed a high K+ -induced fluorescence enhancement (FE) by a factor of 7.7 of the anthracenic emission and a dissociation constant (Kd ) value of 38 mm in water. Further, for 2+K+ , we observed a dual emission behavior at 405 and 505 nm. K+ increases the fluorescence intensity of 2 at 405 nm by a factor of approximately 4.6 and K+ decreases the fluorescence intensity at 505 nm by a factor of about 4.8. Fluorescent probe 2+K+ exhibited a Kd value of approximately 8 mm in Na+ -free solutions and in combined K+ /Na+ solution a similar Kd value of about 9 mm was found, reflecting the high K+ /Na+ selectivity of 2 in water. Therefore, 2 is a promising fluorescent tool to measure ratiometrically and selectively physiologically relevant K+ levels.

Impact of a Mental Health Nursing Training-Programme on the Perceived Recovery-Orientation of Patients and Nurses on Acute Psychiatric Wards: Results of a Pilot Study.

In mental health nursing, recovery-orientation is regarded as a best practice approach for patient care. To assess the effect of an intervention utilising a recovery-oriented approach in acute practice, a controlled pilot trial was conducted. On intervention wards, mental health nurses received special training. Recovery Self-Assessment Scale was used to assess the effects of the training. No statistically significant effects were found, between the experimental conditions. Reasons for this result may be methodological, practical or due an intervention that was not powerful enough. Recovery-oriented intervention studies in mental health nursing should be conducted with caution.

Highly K+ -Selective Fluorescent Probes for Lifetime Sensing of K+ in Living Cells.

The new K+ -selective fluorescent probes 1 and 2 were obtained by CuI -catalyzed 1,3-dipolar azide alkyne cycloaddition (CuAAC) reactions of an alkyne-substituted [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD) ester fluorophore with azido-functionalized N-phenylaza-18-crown-6 ether and N-(o-isopropoxy) phenylaza-18-crown-6 ether, respectively. Probes 1 and 2 allow the detection of K+ in the presence of Na+ in water by fluorescence enhancement (2.2 for 1 at 2000 mm K+ and 2.5 for 2 at 160 mm K+ ). Fluorescence lifetime measurements in the absence and presence of K+ revealed bi-exponential decay kinetics with similar lifetimes, however with different proportions changing the averaged fluorescence decay times (τf(av) ). For 1 a decrease of τf(av) from 12.4 to 9.3 ns and for 2 an increase from 17.8 to 21.8 ns was observed. Variation of the substituent in ortho position of the aniline unit of the N-phenylaza-18-crown-6 host permits the modulation of the Kd value for a certain K+ concentration. For example, substitution of H in 1 by the isopropoxy group (2) decreased the Kd value from >300 mm to 10 mm. 2 was chosen for studying the efflux of K+ from human red blood cells (RBC). Upon addition of the Ca2+ ionophor ionomycin to a RBC suspension in a buffer containing Ca2+ , the fluorescence of 2 slightly rose within 10 min, however, after 120 min a significant increase was observed.

Phase stability of photoreceivers in intersatellite laser interferometers.

A photoreceiver (PR) is required for the opto-electrical conversion of signals in intersatellite laser interferometers. Noise sources that originate or couple in the PR reduce the system carrier-to-noise-density, which is often represented by its phase noise density. In this work, we analyze the common noise sources in a PR used for space-based interferometry. Additionally, we present the results from the characterization of the PRs in GRACE-FO, a mission which will pioneer intersatellite laser interferometry. The estimated phase noise is shot-noise limited at 10-4 rad/Hz1/2 down to 10-2 Hz, almost 4 orders of magnitude below the instrument top level requirement (0.5 rad/Hz1/2). Below 10-2 Hz, the PR finite phase response noise dominates but the levels still comply with the instrument requirement. The sub-mHz noise levels and the PR electronic noise have been identified as key design factors for the LISA PR.

Design of Na+ -Selective Fluorescent Probes: A Systematic Study of the Na+ -Complex Stability and the Na+ /K+ Selectivity in Acetonitrile and Water.

There is a tremendous demand for highly Na+ -selective fluoroionophores to monitor the top analyte Na+ in life science. Here, we report a systematic route to develop highly Na+ /K+ selective fluorescent probes. Thus, we synthesized a set of fluoroionophores 1, 3, 4, 5, 8 and 9 (see Scheme ) to investigate the Na+ /K+ selectivity and Na+ - complex stability in CH3 CN and H2 O. These Na+ -probes bear different 15-crown-5 moieties to bind Na+ stronger than K+ . In the set of the diethylaminocoumarin-substituted fluoroionophores 1-5, the following trend of fluorescence quenching 1>3>2>4>5 in CH3 CN was observed. Therefore, the flexibility of the aza-15-crown-5 moieties in 1-4 determines the conjugation of the nitrogen lone pair with the aromatic ring. As a consequence, 1 showed in CH3 CN the highest Na+ -induced fluorescence enhancement (FE) by a factor of 46.5 and a weaker K+ induced FE of 3.7. The Na+ -complex stability of 1-4 in CH3 CN is enhanced in the following order of 2>4>3>1, assuming that the O-atom of the methoxy group in the ortho-position, as shown in 2, strengthened the Na+ -complex formation. Furthermore, we found for the N-(o-methoxyphenyl)aza-15-crown-5 substituted fluoroionophores 2, 8 and 9 in H2 O, an enhanced Na+ -complex stability in the following order 8>2>9 and an increased Na+ /K+ selectivity in the reverse order 9>2>8. Notably, the Na+ -induced FE of 8 (FEF=10.9), 2 (FEF=5.0) and 9 (FEF=2.0) showed a similar trend associated with a decreased K+ -induced FE [8 (FEF=2.7)>2 (FEF=1.5)>9 (FEF=1.1)]. Here, the Na+ -complex stability and Na+ /K+ selectivity is also influenced by the fluorophore moiety. Thus, fluorescent probe 8 (Kd =48 mm) allows high-contrast, sensitive, and selective Na+ measurements over extracellular K+ levels. A higher Na+ /K+ selectivity showed fluorescent probe 9, but also a higher Kd value of 223 mm. Therefore, 9 is a suitable tool to measure Na+ concentrations up to 300 mm at a fluorescence emission of 614 nm.

Experimental demonstration of deep frequency modulation interferometry.

Experiments for space and ground-based gravitational wave detectors often require a large dynamic range interferometric position readout of test masses with 1 pm/√Hz precision over long time scales. Heterodyne interferometer schemes that achieve such precisions are available, but they require complex optical set-ups, limiting their scalability for multiple channels. This article presents the first experimental results on deep frequency modulation interferometry, a new technique that combines sinusoidal laser frequency modulation in unequal arm length interferometers with a non-linear fit algorithm. We have tested the technique in a Michelson and a Mach-Zehnder Interferometer topology, respectively, demonstrated continuous phase tracking of a moving mirror and achieved a performance equivalent to a displacement sensitivity of 250 pm/Hz at 1 mHz between the phase measurements of two photodetectors monitoring the same optical signal. By performing time series fitting of the extracted interference signals, we measured that the linearity of the laser frequency modulation is on the order of 2% for the laser source used.

A Highly K(+) -Selective Fluorescent Probe - Tuning the K(+) -Complex Stability and the K(+) /Na(+) Selectivity by Varying the Lariat-Alkoxy Unit of a Phenylaza[18]crown-6 Ionophore.

A desirable goal is to synthesize easily accessible and highly K(+) /Na(+) -selective fluoroionophores to monitor physiological K(+) levels in vitro and in vivo. Therefore, highly K(+) /Na(+) -selective ionophores have to be developed. Herein, we obtained in a sequence of only four synthetic steps a set of K(+) -responsive fluorescent probes 4, 5 and 6. In a systematic study, we investigated the influence of the alkoxy substitution in ortho position of the aniline moiety in π-conjugated aniline-1,2,3-triazole-coumarin-fluoroionophores 4, 5 and 6 [R=MeO (4), EtO (5) and iPrO (6)] towards the K(+) -complex stability and K(+) /Na(+) selectivity. The highest K(+) -complex stability showed fluoroionophore 4 with a dissociation constant Kd of 19 mm, but the Kd value increases to 31 mm in combined K(+) /Na(+) solutions, indicating a poor K(+) /Na(+) selectivity. By contrast, 6 showed even in the presence of competitive Na(+) ions equal Kd values (Kd (K+) =45 mm and Kd (K+/Na+) =45 mm) and equal K(+) -induced fluorescence enhancement factors (FEFs=2.3). Thus, the fluorescent probe 6 showed an outstanding K(+) /Na(+) selectivity and is a suitable fluorescent tool to measure physiological K(+) levels in the range of 10-80 mm in vitro. Further, the isopropoxy-substituted N-phenylaza[18]crown-6 ionophore in 6 is a highly K(+) -selective building block with a feasible synthetic route.

Readout for intersatellite laser interferometry: Measuring low frequency phase fluctuations of high-frequency signals with microradian precision.

Precision phase readout of optical beat note signals is one of the core techniques required for intersatellite laser interferometry. Future space based gravitational wave detectors like eLISA require such a readout over a wide range of MHz frequencies, due to orbit induced Doppler shifts, with a precision in the order of µrad/√Hz at frequencies between 0.1 mHz and 1 Hz. In this paper, we present phase readout systems, so-called phasemeters, that are able to achieve such precisions and we discuss various means that have been employed to reduce noise in the analogue circuit domain and during digitisation. We also discuss the influence of some non-linear noise sources in the analogue domain of such phasemeters. And finally, we present the performance that was achieved during testing of the elegant breadboard model of the LISA phasemeter, which was developed in the scope of a European Space Agency technology development activity.

A Highly K(+)-Selective Two-Photon Fluorescent Probe.

A highly K(+)-selective two-photon fluorescent probe for the in vitro monitoring of physiological K(+) levels in the range of 1-100 mM is reported. The two-photon excited fluorescence (TPEF) probe shows a fluorescence enhancement (FE) by a factor of about three in the presence of 160 mM K(+), independently of one-photon (OP, 430 nm) or two-photon (TP, 860 nm) excitation and comparable K(+)-induced FEs in the presence of competitive Na(+) ions. The estimated dissociation constant (Kd ) values in Na(+)-free solutions (Kd (OP) =(28±5) mM and Kd (TP)=(36±6) mM) and in combined K(+)/Na(+) solutions (Kd (OP) =(38±8) mM and Kd (TP)=(46±25) mM) reflecting the high K(+)/Na(+) selectivity of the fluorescent probe. The TP absorption cross-section (σ2PA ) of the TPEF probe+160 mM K(+) is 26 GM at 860 nm. Therefore, the TPEF probe is a suitable tool for the in vitro determination of K(+).

Fluorescence lifetime-based sensing of sodium by an optode.

We report a 1,2,3-triazol fluoroionophore for detecting Na(+) that shows in vitro enhancement in the Na(+)-induced fluorescence intensity and decay time. The Na(+)-selective molecule 1 was incorporated into a hydrogel as a part of a fiber optical sensor. This sensor allows the direct determination of Na(+) in the range of 1-10 mM by measuring reversible fluorescence decay time changes.

Advanced phasemeter for deep phase modulation interferometry.

We present the development of an advanced phasemeter for the deep phase modulation interferometry technique. This technique aims for precise length measurements with a high dynamic range using little optical hardware. The advanced phasemeter uses fast ADCs and an FPGA to implement a design of multiple single-bin Fourier transforms running at high sampling rates. Non-linear noise sources in the design were analyzed and suppressed. A null measurement with an optical beatnote signal using λ = 1064nm was conducted. It showed a sensitivity of 0.8µrad/√Hz below 10Hz and 13.3µrad/√Hz above, with a large dynamic range. The shown performance could enable the measuring of optical path lengths with sensitivities down to 0.14pm/√Hz and 2.3pm/√Hz, respectively, over several fringes in an interferometric setup.