Diffractive optics approach towards subwavelength pixels

Pixel size in cameras and other refractive imaging devices is typically limited by the free-space diffraction. However, a vast majority of semiconductor-based detectors are based on materials with substantially high refractive index. We demonstrate that diffractive optics can be used to take advantage of this high refractive index to reduce effective pixel size of the sensors below free-space diffraction limit. At the same time, diffractive systems encode both amplitude and phase information about the incoming beam into multiple pixels, offering the platform for noise-tolerant imaging with dynamical refocusing. We explore the opportunities opened by high index diffractive optics to reduce sensor size and increase signal-to-noise ratio of imaging structures.Comment: submitted to SPIE-DCS 201

Quantum metrology and its application in biology

Quantum metrology provides a route to overcome practical limits in sensing devices. It holds particular relevance to biology, where sensitivity and resolution constraints restrict applications both in fundamental biophysics and in medicine. Here, we review quantum metrology from this biological context, focusing on optical techniques due to their particular relevance for biological imaging, sensing, and stimulation. Our understanding of quantum mechanics has already enabled important applications in biology, including positron emission tomography (PET) with entangled photons, magnetic resonance imaging (MRI) using nuclear magnetic resonance, and bio-magnetic imaging with superconducting quantum interference devices (SQUIDs). In quantum metrology an even greater range of applications arise from the ability to not just understand, but to engineer, coherence and correlations at the quantum level. In the past few years, quite dramatic progress has been seen in applying these ideas into biological systems. Capabilities that have been demonstrated include enhanced sensitivity and resolution, immunity to imaging artifacts and technical noise, and characterization of the biological response to light at the single-photon level. New quantum measurement techniques offer even greater promise, raising the prospect for improved multi-photon microscopy and magnetic imaging, among many other possible applications. Realization of this potential will require cross-disciplinary input from researchers in both biology and quantum physics. In this review we seek to communicate the developments of quantum metrology in a way that is accessible to biologists and biophysicists, while providing sufficient detail to allow the interested reader to obtain a solid understanding of the field. We further seek to introduce quantum physicists to some of the central challenges of optical measurements in biological science.Comment: Submitted review article, comments and suggestions welcom

Direct imaging of short-range order and its impact on deformation in Ti-6Al.

Chemical short-range order (SRO) within a nominally single-phase solid solution is known to affect the mechanical properties of alloys. While SRO has been indirectly related to deformation, direct observation of the SRO domain structure, and its effects on deformation mechanisms at the nanoscale, has remained elusive. Here, we report the direct observation of SRO in relation to deformation using energy-filtered imaging in a transmission electron microscope (TEM). The diffraction contrast is enhanced by reducing the inelastically scattered electrons, revealing subnanometer SRO-enhanced domains. The destruction of these domains by dislocation planar slip is observed after ex situ and in situ TEM mechanical testing. These results confirm the impact of SRO in Ti-Al alloys on the scale of angstroms. The direct confirmation of SRO in relationship to dislocation plasticity in metals can provide insight into how the mechanical behavior of concentrated solid solutions by the material's thermal history

High-resolution transport-of-intensity quantitative phase microscopy with annular illumination

For quantitative phase imaging (QPI) based on transport-of-intensity equation (TIE), partially coherent illumination provides speckle-free imaging, compatibility with brightfield microscopy, and transverse resolution beyond coherent diffraction limit. Unfortunately, in a conventional microscope with circular illumination aperture, partial coherence tends to diminish the phase contrast, exacerbating the inherent noise-to-resolution tradeoff in TIE imaging, resulting in strong low-frequency artifacts and compromised imaging resolution. Here, we demonstrate how these issues can be effectively addressed by replacing the conventional circular illumination aperture with an annular one. The matched annular illumination not only strongly boosts the phase contrast for low spatial frequencies, but significantly improves the practical imaging resolution to near the incoherent diffraction limit. By incorporating high-numerical aperture (NA) illumination as well as high-NA objective, it is shown, for the first time, that TIE phase imaging can achieve a transverse resolution up to 208 nm, corresponding to an effective NA of 2.66. Time-lapse imaging of in vitro Hela cells revealing cellular morphology and subcellular dynamics during cells mitosis and apoptosis is exemplified. Given its capability for high-resolution QPI as well as the compatibility with widely available brightfield microscopy hardware, the proposed approach is expected to be adopted by the wider biology and medicine community.Comment: This manuscript was originally submitted on 20 Feb. 201

Plasmonic antennas and zero mode waveguides to enhance single molecule fluorescence detection and fluorescence correlation spectroscopy towards physiological concentrations

Single-molecule approaches to biology offer a powerful new vision to elucidate the mechanisms that underpin the functioning of living cells. However, conventional optical single molecule spectroscopy techniques such as F\"orster fluorescence resonance energy transfer (FRET) or fluorescence correlation spectroscopy (FCS) are limited by diffraction to the nanomolar concentration range, far below the physiological micromolar concentration range where most biological reaction occur. To breach the diffraction limit, zero mode waveguides and plasmonic antennas exploit the surface plasmon resonances to confine and enhance light down to the nanometre scale. The ability of plasmonics to achieve extreme light concentration unlocks an enormous potential to enhance fluorescence detection, FRET and FCS. Single molecule spectroscopy techniques greatly benefit from zero mode waveguides and plasmonic antennas to enter a new dimension of molecular concentration reaching physiological conditions. The application of nano-optics to biological problems with FRET and FCS is an emerging and exciting field, and is promising to reveal new insights on biological functions and dynamics.Comment: WIREs Nanomed Nanobiotechnol 201