Measuring gravitational attraction with a lattice atom interferometer.

Despite being the dominant force of nature on large scales, gravity remains relatively elusive to precision laboratory experiments. Atom interferometers are powerful tools for investigating, for example, Earth's gravity1, the gravitational constant2, deviations from Newtonian gravity3-6 and general relativity7. However, using atoms in free fall limits measurement time to a few seconds8, and much less when measuring interactions with a small source mass2,5,6,9. Recently, interferometers with atoms suspended for 70 s in an optical-lattice mode filtered by an optical cavity have been demonstrated10-14. However, the optical lattice must balance Earth's gravity by applying forces that are a billionfold stronger than the putative signals, so even tiny imperfections may generate complex systematic effects. Thus, lattice interferometers have yet to be used for precision tests of gravity. Here we optimize the gravitational sensitivity of a lattice interferometer and use a system of signal inversions to suppress and quantify systematic effects. We measure the attraction of a miniature source mass to be amass = 33.3 ± 5.6stat ± 2.7syst nm s-2, consistent with Newtonian gravity, ruling out 'screened fifth force' theories3,15,16 over their natural parameter space. The overall accuracy of 6.2 nm s-2 surpasses by more than a factor of four the best similar measurements with atoms in free fall5,6. Improved atom cooling and tilt-noise suppression may further increase sensitivity for investigating forces at sub-millimetre ranges17,18, compact gravimetry19-22, measuring the gravitational Aharonov-Bohm effect9,23 and the gravitational constant2, and testing whether the gravitational field has quantum properties24.

Quantum gas mixtures and dual-species atom interferometry in space.

The capability to reach ultracold atomic temperatures in compact instruments has recently been extended into space1,2. Ultracold temperatures amplify quantum effects, whereas free fall allows further cooling and longer interactions time with gravity-the final force without a quantum description. On Earth, these devices have produced macroscopic quantum phenomena such as Bose-Einstein condensates (BECs), superfluidity, and strongly interacting quantum gases3. Terrestrial quantum sensors interfering the superposition of two ultracold atomic isotopes have tested the universality of free fall (UFF), a core tenet of Einstein's classical gravitational theory, at the 10-12 level4. In space, cooling the elements needed to explore the rich physics of strong interactions or perform quantum tests of the UFF has remained elusive. Here, using upgraded hardware of the multiuser Cold Atom Lab (CAL) instrument aboard the International Space Station (ISS), we report, to our knowledge, the first simultaneous production of a dual-species BEC in space (formed from 87Rb and 41K), observation of interspecies interactions, as well as the production of 39K ultracold gases. Operating a single laser at a 'magic wavelength' at which Rabi rates of simultaneously applied Bragg pulses are equal, we have further achieved the first spaceborne demonstration of simultaneous atom interferometry with two atomic species (87Rb and 41K). These results are an important step towards quantum tests of UFF in space and will allow scientists to investigate aspects of few-body physics, quantum chemistry and fundamental physics in new regimes without the perturbing asymmetry of gravity.

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.

Label-free optical detection of bioelectric potentials using electrochromic thin films.

Understanding how a network of interconnected neurons receives, stores, and processes information in the human brain is one of the outstanding scientific challenges of our time. The ability to reliably detect neuroelectric activities is essential to addressing this challenge. Optical recording using voltage-sensitive fluorescent probes has provided unprecedented flexibility for choosing regions of interest in recording neuronal activities. However, when recording at a high frame rate such as 500 to 1,000 Hz, fluorescence-based voltage sensors often suffer from photobleaching and phototoxicity, which limit the recording duration. Here, we report an approach called electrochromic optical recording (ECORE) that achieves label-free optical recording of spontaneous neuroelectrical activities. ECORE utilizes the electrochromism of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) thin films, whose optical absorption can be modulated by an applied voltage. Being based on optical reflection instead of fluorescence, ECORE offers the flexibility of an optical probe without suffering from photobleaching or phototoxicity. Using ECORE, we optically recorded spontaneous action potentials in cardiomyocytes, cultured hippocampal and dorsal root ganglion neurons, and brain slices. With minimal perturbation to cells, ECORE allows long-term optical recording over multiple days.

Perspective: Emerging strategies for determining atomic-resolution structures of macromolecular complexes within cells.

In principle, electron cryo-tomography (cryo-ET) of thin portions of cells provides high-resolution images of the three-dimensional spatial arrangement of all members of the proteome. In practice, however, radiation damage creates a tension between recording images at many different tilt angles, but at correspondingly reduced exposure levels, versus limiting the number of tilt angles in order to improve the signal-to-noise ratio (SNR). Either way, it is challenging to read the available information out at the level of atomic structure. Here, we first review work that explores the optimal strategy for data collection, which currently seems to favor the use of a limited angular range for tilting the sample or even the use of a single image to record the high-resolution information. Looking then to the future, we point to the alternative of so-called "deconvolution microscopy", which may be applied to tilt-series or optically-sectioned, focal series data. Recording data as a focal series has the advantage that little or no translational alignment of frames might be needed, and a three-dimensional reconstruction might require only 2/3 the number of images as does standard tomography. We also point to the unexploited potential of phase plates to increase the contrast, and thus to reduce the electron exposure levels while retaining the ability align and merge the data. In turn, using much lower exposures per image could have the advantage that high-resolution information is retained throughout the full data-set, whether recorded as a tilt series or a focal series of images.

Dual-Color Optical Recording of Bioelectric Potentials by Polymer Electrochromism.

Optical recording based on voltage-sensitive fluorescent reporters allows for spatial flexibility of measuring from desired cells, but photobleaching and phototoxicity of the fluorescent labels often limit their sensitivity and recording duration. Voltage-dependent optical absorption, rather than fluorescence, of electrochromic materials, would overcome these limitations to achieve long-term optical recording of bioelectrical signals. Electrochromic materials such as PEDOT:PSS possess the property that an applied voltage can either increase or decrease the light absorption depending on the wavelength. In this work, we harness this anticorrelated light absorption at two different wavelengths to significantly improve the signal detection. With dual-color detection, electrical activity from cells produces signals of opposite polarity, while artifacts, mechanical motions, and technical noises are uncorrelated or positively correlated. Using this technique, we are able to optically record cardiac action potentials with a high signal-to-noise ratio, 10 kHz sampling rate, >15 min recording duration, and no time-dependent degradation of the signal. Furthermore, we can reliably perform multiple recording sessions from the same culture for over 25 days.

Laser phase plate for transmission electron microscopy.

Transmission electron microscopy (TEM) of rapidly frozen biological specimens, or cryo-EM, would benefit from the development of a phase plate for in-focus phase contrast imaging. Several types of phase plates have been investigated, but rapid electrostatic charging of all such devices has hindered these efforts. Here, we demonstrate electron phase manipulation with a high-intensity continuous-wave laser beam, and use it as a phase plate for TEM. We demonstrate the laser phase plate by imaging an amorphous carbon film. The laser phase plate provides a stable and tunable phase shift without electrostatic charging or unwanted electron scattering. These results suggest the possibility for dose-efficient imaging of unstained biological macromolecules and cells.

Optical Electrophysiology: Toward the Goal of Label-Free Voltage Imaging.

Measuring and monitoring the electrical signals transmitted between neurons is key to understanding the communication between neurons that underlies human perception, information processing, and decision-making. While electrode-based electrophysiology has been the gold standard, optical electrophysiology has opened up a new area in the past decade. Voltage-dependent fluorescent reporters enable voltage imaging with high spatial resolution and flexibility to choose recording locations. However, they exhibit photobleaching as well as phototoxicity and may perturb the physiology of the cell. Label-free optical electrophysiology seeks to overcome these hurdles by detecting electrical activities optically, without the incorporation of exogenous fluorophores in cells. For example, electrochromic optical recording detects neuroelectrical signals via a voltage-dependent color change of extracellular materials, and interferometric optical recording monitors membrane deformations that accompany electrical activities. Label-free optical electrophysiology, however, is in an early stage, and often has limited sensitivity and temporal resolution. In this Perspective, we review the recent progress to overcome these hurdles. We hope this Perspective will inspire developments of label-free optical electrophysiology techniques with high recording sensitivity and temporal resolution in the near future.

Observation of the Relativistic Reversal of the Ponderomotive Potential.

The secular dynamics of a nonrelativistic charged particle in an electromagnetic wave can be described by the ponderomotive potential. Although ponderomotive electron-laser interactions at relativistic velocities are important for emerging technologies from laser-based particle accelerators to laser-enhanced electron microscopy, the effects of special relativity on the interaction have only been studied theoretically. Here, we use a transmission electron microscope to measure the position-dependent phase shift imparted to a relativistic electron wave function when it traverses a standing laser wave. The kinetic energy of the electrons is varied between 80 and 300 keV, and the laser standing wave has a continuous-wave intensity of 175 GW/cm^{2}. In contrast to the nonrelativistic case, we demonstrate that the phase shift depends on both the electron velocity and the wave polarization, confirming the predictions of a quasiclassical theory of the interaction. Remarkably, if the electron's speed is greater than 1/sqrt[2] of the speed of light, the phase shift at the electric field nodes of the wave can exceed that at the antinodes. In this case there exists a polarization such that the phase shifts at the nodes and antinodes are equal, and the electron does not experience Kapitza-Dirac diffraction. Our results thus provide new capabilities for coherent electron beam manipulation.

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.

Direct glucosone-based synthesis and HILIC-ESI-MS/MS characterization of N-terminal fructosylated valine and valylhistidine for validation of enzymatic HbA1c assays in the diagnosis of diabetes mellitus.

Naturally occurring fructosamines are of high clinical significance due to their potential use in diabetes mellitus monitoring (quantification of fructosylated hemoglobin, HbA1c) or for the investigation of their reactivity in consecutive reactions and harmfulness towards the organism. Here we report the specific synthesis of the fructosylated dipeptide L-valyl-L-histidine (Fru-Val-His) and fructosylated L-valine (Fru-Val). Both are basic tools for the development and validation of enzymatic HbA1c assays. The two fructosamine derivatives were synthesized via a protected glucosone intermediate which was coupled to the primary amine of Val or Val-His, performing a reductive amination reaction. Overall yields starting from fructose were 36% and 34% for Fru-Val and Fru-Val-His, respectively. Both compounds were achieved in purities > 90%. A HILIC-ESI-MS/MS method was developed for routine analysis of the synthesized fructosamines, including starting materials and intermediates. The presented method provides a well-defined and efficient synthesis protocol with purification steps and characterization of the desired products. The functionality of the fructosylated dipeptide has been thoroughly tested in an enzymatic HbA1c assay, showing its concentration-dependent oxidative degradation by fructosyl-peptide oxidases (FPOX). Graphical abstract.

Efficient Adiabatic Spin-Dependent Kicks in an Atom Interferometer.

We present an atom interferometry technique in which the beam splitter is split into two separate operations. A microwave pulse first creates a spin-state superposition, before optical adiabatic passage spatially separates the arms of that superposition. Despite using a thermal atom sample in a small (600 µm) interferometry beam, this procedure delivers an efficiency of 99% per ℏk of momentum separation. Utilizing this efficiency, we first demonstrate interferometry with up to 16ℏk momentum splitting and free-fall limited interrogation times. We then realize a single-source gradiometer, in which two interferometers measuring a relative phase originate from the same atomic wave function. Finally, we demonstrate a resonant interferometer with over 100 adiabatic passages, and thus over 400ℏk total momentum transferred.

Recoil-Sensitive Lithium Interferometer without a Subrecoil Sample.

We report simultaneous conjugate Ramsey-Bordé interferometers with a sample of low-mass (lithium-7) atoms at 50 times the recoil temperature. We optically pump the atoms to a magnetically insensitive state using the 2S_{1/2}-2P_{1/2} line. Fast stimulated Raman beam splitters address a broad velocity class and unavoidably drive two conjugate interferometers that overlap spatially. We show that detecting the summed interference signals of both interferometers, using state labeling, allows recoil measurements and suppression of phase noise from vibrations. The use of "warm" atoms allows for simple, efficient, and high-flux atom sources and broadens the applicability of recoil-sensitive interferometry to particles that remain difficult to trap and cool.

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.

Rotational Spectroscopy of the Lowest Energy Conformer of 2-Cyanobutane.

Isopropyl cyanide was recently detected in space as the first branched alkyl compound. Its abundance with respect to n-propyl cyanide in the Galactic center source Sagittarius B2(N2) is about 0.4. Astrochemical model calculations suggest that for the heavier homologue butyl cyanide the branched isomers dominate over the unbranched n-butyl cyanide and that 2-cyanobutane is the most abundant isomer. We have studied the rotational spectrum of 2-cyanobutane between 2 and 24 GHz using Fourier transform microwave spectroscopy and between 36 and 402 GHz employing (sub)millimeter absorption spectroscopy. Transitions of the lowest energy conformer were identified easily. Its rotational spectrum is very rich, and the quantum numbers J and Ka reach values of 111 and 73, respectively. This wealth of data yielded rotational and centrifugal distortion parameters up to tenth order, diagonal and one off-diagonal 14N nuclear quadrupole coupling parameters, and one nuclear spin-rotation coupling parameter. We have also carried out quantum chemical calculations in part to facilitate the assignments. The molecule 2-cyanobutane was not found in the present ALMA data of Sagittarius B2(N2), but it may be found in the more sensitive data that have been completed very recently in the ALMA Cycle 4.

Laser frequency stabilization by combining modulation transfer and frequency modulation spectroscopy.

We present a hybrid laser frequency stabilization method combining modulation transfer spectroscopy (MTS) and frequency modulation spectroscopy (FMS) for the cesium D2 transition. In a typical pump-probe setup, the error signal is a combination of the DC-coupled MTS error signal and the AC-coupled FMS error signal. This combines the long-term stability of the former with the high signal-to-noise ratio of the latter. In addition, we enhance the long-term frequency stability with laser intensity stabilization. By measuring the frequency difference between two independent hybrid spectroscopies, we investigate the short-and long-term stability. We find a long-term stability of 7.8 kHz characterized by a standard deviation of the beating frequency drift over the course of 10 h and a short-term stability of 1.9 kHz characterized by an Allan deviation of that at 2 s of integration time.

A precision measurement of the gravitational redshift by the interference of matter waves.

One of the central predictions of metric theories of gravity, such as general relativity, is that a clock in a gravitational potential U will run more slowly by a factor of 1 + U/c(2), where c is the velocity of light, as compared to a similar clock outside the potential. This effect, known as gravitational redshift, is important to the operation of the global positioning system, timekeeping and future experiments with ultra-precise, space-based clocks (such as searches for variations in fundamental constants). The gravitational redshift has been measured using clocks on a tower, an aircraft and a rocket, currently reaching an accuracy of 7 x 10(-5). Here we show that laboratory experiments based on quantum interference of atoms enable a much more precise measurement, yielding an accuracy of 7 x 10(-9). Our result supports the view that gravity is a manifestation of space-time curvature, an underlying principle of general relativity that has come under scrutiny in connection with the search for a theory of quantum gravity. Improving the redshift measurement is particularly important because this test has been the least accurate among the experiments that are required to support curved space-time theories.

High-Resolution Atom Interferometers with Suppressed Diffraction Phases.

We experimentally and theoretically study the diffraction phase of large-momentum transfer beam splitters in atom interferometers based on Bragg diffraction. We null the diffraction phase and increase the sensitivity of the interferometer by combining Bragg diffraction with Bloch oscillations. We demonstrate agreement between experiment and theory, and a 1500-fold reduction of the diffraction phase, limited by measurement noise. In addition to reduced systematic effects, our interferometer has high contrast with up to 4.4×10(6) radians of phase difference, and a resolution in the fine structure constant of δα/α=0.25 ppb in 25 h of integration time.