Microfluidic-based linear-optics label-free imager.

Linear optics based nanoscopy previously reached resolution beyond the diffraction limit, illuminating samples in the visible light regime while allowing light to interact with freely moving metallic nanoparticles. However, the hydrodynamics governing the nanoparticle motion used to scan the sample is very complex and has low probability of achieving appropriate and fast mapping in practice. Hence, an implementation of the technique on real biological samples has not been demonstrated so far. Moreover, a suitable way to perform controlled nanoparticle scanning of biological samples is required. Here we show a solution where a microfluidic channel is used to flow and trap biological samples inside a water droplet along with suspended nanoparticles surrounded by silicone oil. The evanescent light scattered from the sample and is rescattered by the nanoparticles in the vicinity. This encodes the sub-wavelength features of the sample which can later on be decoded and reconstructed from measurements in the far field. The microfluidic system-controlled flow allows better nanoparticle scanning of the sample and maintains an isolated system for each sample in each droplet. A more localized scan at the droplet water/oil interface is also conducted using amphiphilic nanoparticles where their hydrophilic side is constrained to the droplet and their hydrophobic side is constrained to the oil. This allows higher probability of capturing evanescent fields closer to their origin, yielding better resolution and a higher signal to noise ratio. Using this system, we obtained images of an E. coli sample and demonstrated how the method yield fine resolution of the sample contours. To the best of our knowledge, this is the first time that a linear and label free optics imaging process was performed using a micro-fluidic device.

Drag controlled formation of polymeric colloids with optical traps.

Optical trapping is a powerful optical manipulation technique for controlling various mesoscopic systems that allows formation of tailor-made polymeric micro-sized colloids by directed coalescence of nucleation sites. However, control over the size of a single colloid requires constant monitoring of the growth process and deactivation of the optical trap once it reaches the required dimensions. Moreover, producing more than one colloid requires moving the sample to a pristine location where the process must be repeated. Here, we present a novel method for continuous control over formation of polydimethylsiloxane colloids based on directed coalescence induced by optical traps under flow inside microfluidic channels. Once the drag force on a growing colloid exceeds the trapping force, it leaves the optical trap, and a new colloid starts to form at the same location. We demonstrate repeatability of the process and selectively produce colloids with radii of ∼1-14 µm by controlling the laser intensity and flow rate. In addition, holographic optical tweezers are used to show how multiple optical traps in 3D could be used to influence a significant cross section of the micro-channel, thus forming a light-controlled assembly line for colloidal formation.

Imaging of nanoparticle dynamics in live and apoptotic cells using temporally-modulated polarization.

Gold nanoparticles are widely exploited in phototherapy. Owing to their biocompatibility and their strong visible-light surface plasmonic resonance, these particles also serve as contrast agents for cell image enhancement and super-resolved imaging. Yet, their optical signal is still insufficiently strong for many important real-life applications. Also, the differentiation between adjacent nanoparticles is usually limited by the optical resolution and the orientations of non-spherical particles are unknown. These limitations hamper the progress in cell research by direct optical microscopy and narrow the range of phototherapy applications. Here we demonstrate exploiting the optical anisotropy of non-spherical nanoparticles to achieve super-resolution in live cell imaging and to resolve the intracellular nanoparticle orientations. In particular, by modulating the light polarization and taking advantage of the polarization-dependence of gold nanorod optical properties, we realize the 'lock-in amplification', widely-used in electronic engineering, to achieve image enhancement in live cells and in cells that undergo apoptotic changes.

Plasma dispersion effect based super-resolved imaging in silicon.

We present here a new method for shaping a pulsed IR (λ = 1550nm) laser beam in silicon. The shaping is based on the plasma dispersion effect (PDE). The shaping is done by a second pulsed pump laser beam at 532nm (in either a Gaussian mode or a donut mode) which simultaneously and collinearly illuminates the silicon's surface with the IR beam. Following the PDE, and in proportion to its spatial intensity distribution, the 532nm laser beam shapes the point spread function (PSF) by controlling the lateral transmission of the IR probe beam. The use of this probe in a laser scanning microscope allows imaging and a wide range of contactless electrical measurements in silicon integrated circuits (IC) being under operation. We propose this shaping method to overcome the diffraction resolution limit in silicon microscopy on and deep under the silicon surface.

Color image identification and reconstruction using artificial neural networks on multimode fiber images: towards an all-optical design.

The rapid growth of applications that rely on artificial neural network (ANN) concepts gives rise to a staggering increase in the demand for hardware implementations of neural networks. New types of hardware that can support the requirements of high-speed associative computing while maintaining low power consumption are sought, and optical artificial neural networks fit the task well. Inherently, optical artificial neural networks can be faster, support larger bandwidth, and produce less heat than their electronic counterparts. Here we propose the design of an optical ANN-based imaging system that has the ability to self-study image signals from an incoherent light source in different colors. Our design consists of a combination of a multimode fiber and a multi-core optical fiber realizing a neural network. We show that the signals, transmitted through the multimode fiber, can be used for image identification purposes and can also be reconstructed using ANNs with a low number of nodes. An all-optical solution can then be achieved by realizing these networks with the multi-core optical neural network fiber.

Non-labeled lensless micro-endoscopic approach for cellular imaging through highly scattering media.

We describe an imaging approach based on an optical setup made up of a miniature, lensless, minimally invasive endoscope scanning a sample and matching post processing techniques that enable enhanced imaging capabilities. The two main scopes of this article are that this approach enables imaging beyond highly scattering medium and increases the resolution and signal to noise levels reaching single cell imaging. Our approach has more advantages over ordinary endoscope setups and other imaging techniques. It is not mechanically limited by a lens, the stable but flexible fiber can acquire images over long time periods (unlike current imaging methods such as OCT etc.), and the imaging can be obtained at a certain working distance above the surface, without interference to the imaged object. Fast overlapping scans enlarge the region of interest, enhance signal to noise levels and can also accommodate post-processing, super-resolution algorithms. Here we present that due to the setup properties, the overlapping scans also lead to dramatic enhancement of non-scattered signal to scattered noise. This enables imaging through highly scattering medium. We discuss results obtained from in vitro investigation of weak signals of ARPE cells, rat retina, and scattered signals from polydimethylsiloxane (PDMS) microchannels filled with hemoglobin and covered by intralipids consequently mimicking blood capillaries and the epidermis of human skin. The development of minimally invasive procedures and methodologies for imaging through scattering medium such as tissues can vastly enhance biomedical diagnostic capabilities for imaging internal organs. We thereby propose that our method may be used for such tasks in vivo.

Optical-tweezing-based linear-optics nanoscopy.

Previous works reported that linear optics could be used to observe sub-wavelength features with a conventional optical microscope. Yet, the ability to reach a sub-200 nm resolution with a visible light remains limited. We present a novel widely-applicable method, where particle trapping is employed to overcome this limit. The combination of the light scattered by the sample and by the trapped particles encodes super-resolution information, which we decode by post image processing, with the trapped particle locations predetermined. As the first proof of concept our method successfully resolved sample characteristic features down to 100 nm. Improved performance is achieved with the fluorescence of the trapped particles employed. Further improvement may be attained with trapped particles of a smaller size.