High-speed in vitro intensity diffraction tomography

We demonstrate a label-free, scan-free intensity diffraction tomography technique utilizing annular illumination (aIDT) to rapidly characterize large-volume three-dimensional (3-D) refractive index distributions in vitro. By optimally matching the illumination geometry to the microscope pupil, our technique reduces the data requirement by 60 times to achieve high-speed 10-Hz volume rates. Using eight intensity images, we recover volumes of ∼350 μm  ×  100 μm  ×  20  μm, with near diffraction-limited lateral resolution of   ∼  487  nm and axial resolution of   ∼  3.4  μm. The attained large volume rate and high-resolution enable 3-D quantitative phase imaging of complex living biological samples across multiple length scales. We demonstrate aIDT’s capabilities on unicellular diatom microalgae, epithelial buccal cell clusters with native bacteria, and live Caenorhabditis elegans specimens. Within these samples, we recover macroscale cellular structures, subcellular organelles, and dynamic micro-organism tissues with minimal motion artifacts. Quantifying such features has significant utility in oncology, immunology, and cellular pathophysiology, where these morphological features are evaluated for changes in the presence of disease, parasites, and new drug treatments. Finally, we simulate the aIDT system to highlight the accuracy and sensitivity of the proposed technique. aIDT shows promise as a powerful high-speed, label-free computational microscopy approach for applications where natural imaging is required to evaluate environmental effects on a sample in real time.https://arxiv.org/abs/1904.06004Accepted manuscrip

Interferometric detection and enumeration of viral particles using Si-based microfluidics

Single-particle interferometric reflectance imaging sensor enables optical visualization and characterization of individual nanoparticles without any labels. Using this technique, we have shown end-point and real-time detection of viral particles using laminate-based active and passive cartridge configurations. Here, we present a new concept for low-cost microfluidic integration of the sensor chips into compact cartridges through utilization of readily available silicon fabrication technologies. This new cartridge configuration will allow simultaneous detection of individual virus binding events on a 9-spot microarray, and provide the needed simplicity and robustness for routine real-time operation for discrete detection of viral particles in a multiplex format.This work was supported in part by a research contract with the ASELSAN Research Center, Ankara, Turkey, and in part by the European Union's Horizon 2020 FET Open program under Grant 766466-INDEX. (ASELSAN Research Center, Ankara, Turkey; 766466-INDEX - European Union's Horizon 2020 FET Open program)First author draf

Molecular Contrast Optical Coherence Tomography: A Review

This article reviews the current state of research on the use of molecular contrast agents in optical coherence tomography (OCT) imaging techniques. After a brief discussion of the basic principle of OCT and the importance of incorporating molecular contrast agent usage into this imaging modality, we shall present an overview of the different molecular contrast OCT (MCOCT) methods that have been developed thus far. We will then discuss several important practical issues that define the possible range of contrast agent choice, the design criteria for engineered molecular contrast agent and the implementability of a given MCOCT method for clinical or biological applications. We will conclude by outlining a few areas of pursuit that deserve a greater degree of research and development

Investigating ultrasound–light interaction in scattering media

Significance: Ultrasound-assisted optical imaging techniques, such as ultrasound-modulated optical tomography, allow for imaging deep inside scattering media. In these modalities, a fraction of the photons passing through the ultrasound beam is modulated. The efficiency by which the photons are converted is typically referred to as the ultrasound modulation’s “tagging efficiency.” Interestingly, this efficiency has been defined in varied and discrepant fashion throughout the scientific literature. Aim: The aim of this study is the ultrasound tagging efficiency in a manner consistent with its definition and experimentally verify the contributive (or noncontributive) relationship between the mechanisms involved in the ultrasound optical modulation process. Approach: We adopt a general description of the tagging efficiency as the fraction of photons traversing an ultrasound beam that is frequency shifted (inclusion of all frequency-shifted components). We then systematically studied the impact of ultrasound pressure and frequency on the tagging efficiency through a balanced detection measurement system that measured the power of each order of the ultrasound tagged light, as well as the power of the unmodulated light component. Results: Through our experiments, we showed that the tagging efficiency can reach 70% in a scattering phantom with a scattering anisotropy of 0.9 and a scattering coefficient of 4  mm⁻¹ for a 1-MHz ultrasound with a relatively low (and biomedically acceptable) peak pressure of 0.47 MPa. Furthermore, we experimentally confirmed that the two ultrasound-induced light modulation mechanisms, particle displacement and refractive index change, act in opposition to each other. Conclusion: Tagging efficiency was quantified via simulation and experiments. These findings reveal avenues of investigation that may help improve ultrasound-assisted optical imaging techniques

Particulate airborne impurities

The cumulative effects of air pollutants are of principal concern in research on environmental protection in Sweden. Post-industrial society has imposed many limits on emitted air pollutants, yet the number of reports on the negative effects from them is increasing, largely due to human activity in the form of industrial emissions and increased traffic flows. Rising concerns over the health effects from airborne particulate matter (PM) stem from in vitro, in vivo, and cohort studies revealing effects of mostly negative nature. Full insight into the health effects from PM can only be achieved through practical investigation of the mode of toxicity from distinct types of particles and requires techniques for their identification, monitoring, and the production of model fractions for health studies. To this effect, comprehensive collection and chemical analysis of particulates at the origin of emission was performed in order to provide clearer insight into the nature of the particulates at exposure and add detail to aid risk assessment. Methods of capturing particles and analyzing their chemical nature were devised using scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS). Furthermore, taking the approach of in vitro cytotoxicity testing, nanoparticles of types typical to automotive emissions, were synthesized and extensively characterized using SEM-EDS, X-ray diffraction (XRD), transmission electron microscopy (TEM),dynamic light scattering (DLS), and nanoparticle tracking analysis (NTA). The produced model magnetite and palladium nanoparticles were found to induce toxicity in human pulmonary epithelial cells (A549 and PBEC) as well as impact severely on immunological and renal cells (221 B- and 293T-cells) in a dose-dependent manner

Multi-contrast imaging and digital refocusing on a mobile microscope with a domed LED array

We demonstrate the design and application of an add-on device for improving the diagnostic and research capabilities of CellScope--a low-cost, smartphone-based point-of-care microscope. We replace the single LED illumination of the original CellScope with a programmable domed LED array. By leveraging recent advances in computational illumination, this new device enables simultaneous multi-contrast imaging with brightfield, darkfield, and phase imaging modes. Further, we scan through illumination angles to capture lightfield datasets, which can be used to recover 3D intensity and phase images without any hardware changes. This digital refocusing procedure can be used for either 3D imaging or software-only focus correction, reducing the need for precise mechanical focusing during field experiments. All acquisition and processing is performed on the mobile phone and controlled through a smartphone application, making the computational microscope compact and portable. Using multiple samples and different objective magnifications, we demonstrate that the performance of our device is comparable to that of a commercial microscope. This unique device platform extends the field imaging capabilities of CellScope, opening up new clinical and research possibilities