Optical constraints on two-photon voltage imaging.

Significance: Genetically encoded voltage indicators (GEVIs) are a valuable tool for studying neural circuits , but the relative merits and limitations of one-photon (1P) versus two-photon (2P) voltage imaging are not well characterized.

Aim: We consider the optical and biophysical constraints particular to 1P and 2P voltage imaging and compare the imaging properties of commonly used GEVIs under 1P and 2P excitation.

Approach: We measure the brightness and voltage sensitivity of voltage indicators from commonly used classes under 1P and 2P illumination.

Optical constraints on two-photon voltage imaging.

Significance: Genetically encoded voltage indicators (GEVIs) are a valuable tool for studying neural circuits , but the relative merits and limitations of one-photon (1P) vs. two-photon (2P) voltage imaging are not well characterized.

Aim: We consider the optical and biophysical constraints particular to 1P and 2P voltage imaging and compare the imaging properties of commonly used GEVIs under 1P and 2P excitation.

A bioelectrical phase transition patterns the first vertebrate heartbeats.

A regular heartbeat is essential to vertebrate life. In the mature heart, this function is driven by an anatomically localized pacemaker. By contrast, pacemaking capability is broadly distributed in the early embryonic heart, raising the question of how tissue-scale activity is first established and then maintained during embryonic development.

Voltage dynamics of dendritic integration and back-propagation .

Neurons integrate synaptic inputs within their dendrites and produce spiking outputs, which then propagate down the axon and back into the dendrites where they contribute to plasticity. Mapping the voltage dynamics in dendritic arbors of live animals is crucial for understanding neuronal computation and plasticity rules. Here we combine patterned channelrhodopsin activation with dual-plane structured illumination voltage imaging, for simultaneous perturbation and monitoring of dendritic and somatic voltage in Layer 2/3 pyramidal neurons in anesthetized and awake mice.

Mapping memories: pulse-chase labeling reveals AMPA receptor dynamics during memory formation.

A tool to map changes in synaptic strength during a defined time window could provide powerful insights into the mechanisms governing learning and memory. We developed a technique, Extracellular Protein Surface Labeling in Neurons (EPSILON), to map α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) insertion by pulse-chase labeling of surface AMPARs with membrane-impermeable dyes. This approach allows for single-synapse resolution maps of plasticity in genetically targeted neurons during memory formation.

Video-based pooled screening yields improved far-red genetically encoded voltage indicators.

Video-based screening of pooled libraries is a powerful approach for directed evolution of biosensors because it enables selection along multiple dimensions simultaneously from large libraries. Here we develop a screening platform, Photopick, which achieves precise phenotype-activated photoselection over a large field of view (2.3 × 2.

Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells.

Back-propagating action potentials (bAPs) regulate synaptic plasticity by evoking voltage-dependent calcium influx throughout dendrites. Attenuation of bAP amplitude in distal dendritic compartments alters plasticity in a location-specific manner by reducing bAP-dependent calcium influx. However, it is not known if neurons exhibit branch-specific variability in bAP-dependent calcium signals, independent of distance-dependent attenuation.

Which Way Does Stimulated Emission Go?

Is it possible to form an image using light produced by stimulated emission? Here we study light scatter off an assembly of excited chromophores. Due to the Optical Theorem, stimulated emission is necessarily accompanied by excited state Rayleigh scattering. Both processes can be used to form images, though they have different dependencies on scattering direction, wavelength and chromophore configuration.

Characterization of a novel automated microfiltration device for the efficient isolation and analysis of circulating tumor cells from clinical blood samples.

The detection and analysis of circulating tumor cells (CTCs) may enable a broad range of cancer-related applications, including the identification of acquired drug resistance during treatments. However, the non-scalable fabrication, prolonged sample processing times, and the lack of automation, associated with most of the technologies developed to isolate these rare cells, have impeded their transition into the clinical practice. This work describes a novel membrane-based microfiltration device comprised of a fully automated sample processing unit and a machine-vision-enabled imaging system that allows the efficient isolation and rapid analysis of CTCs from blood.

Benchmarking an 11-qubit quantum computer.

The field of quantum computing has grown from concept to demonstration devices over the past 20 years. Universal quantum computing offers efficiency in approaching problems of scientific and commercial interest, such as factoring large numbers, searching databases, simulating intractable models from quantum physics, and optimizing complex cost functions. Here, we present an 11-qubit fully-connected, programmable quantum computer in a trapped ion system composed of 13 Yb ions.

High-Throughput Automated Microscopy of Circulating Tumor Cells.

Circulating tumor cells (CTCs) have the potential of becoming the gold standard marker for cancer diagnosis, prognosis and monitoring. However, current methods for its isolation and characterization suffer from equipment variability and human operator error that hinder its widespread use. Here we report the design and construction of a fully automated high-throughput fluorescence microscope that enables the imaging and classification of cancer cells that were labeled by immunostaining procedures.

Demonstration of Two-Atom Entanglement with Ultrafast Optical Pulses.

We demonstrate quantum entanglement of two trapped atomic ion qubits using a sequence of ultrafast laser pulses. Unlike previous demonstrations of entanglement mediated by the Coulomb interaction, this scheme does not require confinement to the Lamb-Dicke regime and can be less sensitive to ambient noise due to its speed. To elucidate the physics of an ultrafast phase gate, we generate a high entanglement rate using just ten pulses, each of ∼20  ps duration, and demonstrate an entangled Bell state with (76±1)% fidelity.

Ultrafast creation of large Schrödinger cat states of an atom.

Mesoscopic quantum superpositions, or Schrödinger cat states, are widely studied for fundamental investigations of quantum measurement and decoherence as well as applications in sensing and quantum information science. The generation and maintenance of such states relies upon a balance between efficient external coherent control of the system and sufficient isolation from the environment. Here we create a variety of cat states of a single trapped atom's motion in a harmonic oscillator using ultrafast laser pulses.

Active stabilization of ion trap radiofrequency potentials.

We actively stabilize the harmonic oscillation frequency of a laser-cooled atomic ion confined in a radiofrequency (rf) Paul trap by sampling and rectifying the high voltage rf applied to the trap electrodes. We are able to stabilize the 1 MHz atomic oscillation frequency to be better than 10 Hz or 10 ppm. This represents a suppression of ambient noise on the rf circuit by 34 dB.

Sensing Atomic Motion from the Zero Point to Room Temperature with Ultrafast Atom Interferometry.

We sense the motion of a trapped atomic ion using a sequence of state-dependent ultrafast momentum kicks. We use this atom interferometer to characterize a nearly pure quantum state with n=1 phonon and accurately measure thermal states ranging from near the zero-point energy to n[over ¯]~10^{4}, with the possibility of extending at least 100 times higher in energy. The complete energy range of this method spans from the ground state to far outside of the Lamb-Dicke regime, where atomic motion is greater than the optical wavelength.

Intermodal energy transfer in a tapered optical fiber: optimizing transmission.

We present an experimental and theoretical study of the energy transfer between modes during the tapering process of an optical nanofiber through spectrogram analysis. The results allow optimization of the tapering process, and we measure transmission in excess of 99.95% for the fundamental mode.