Nonlinear microscopy for failure analysis of CMOS integrated circuits in the vectorial focusing regime

This thesis focuses on the development of techniques for enhancing the spatial resolution and localisation precision in the sub-surface microscopy for failure analysis in semiconductor integrated circuits (ICs). Highest spatial resolutions are obtained by implementing solid immersion lenses (SIL), which provide unsurpassed numerical aperture (NA) for sub-surface microscopy. These high NA conditions mean that scalar diffraction theory is no longer valid and a vectorial focusing description should be applied to accurately describe the focal plane electric field distribution. Vectorial theory predicts that under high NA conditions a linearly polarised (LP) light focuses to a spot that is extended along the electric field vector, but radially polarised (RP) light is predicted to form a circular spot whose diameter equals the narrower dimension obtained with linear polarisation. By implementing a novel liquid-crystal (LC) radial polarisation converter (RPC) this effect was studied for both two-photon optical-beam-induced current (TOBIC) microscopy and two-photon laser assisted device alteration (2pLADA) techniques, showing a resolution and localisation improvement using the RP beam. By comparing images of the same structural features obtained using linear, circular and radial polarisations imaging and localisation resolutions both approaching 100 nm were demonstrated. The obtained experimental results were in good agreement with modelling and were consistent with theoretically predicted behaviour. Certain artefacts were observed under radial polarisation, which were thought to result from the extended depth of focus and the significant longitudinal field component. In any application these effects must be considered alongside the benefits of the symmetric field distribution in the focal plane. While SIL sub-surface microscopy offers unmatched spatial resolutions, it is prone to being severely degraded by aberrations arising from inaccurate dimensions of the SIL, imprecise substrate thickness or imperfect contact between SIL and substrate. It is in this context that techniques to identify and even mitigate aberrations in the system are important. A simple approach is demonstrated for revealing the presence of chromatic and spherical aberrations by measuring the two-photon autocorrelation of the pulses at the focal plane inside the sample. In the case of aberration free imaging, it was shown both theoretically and experimentally that the planes of the maximum autocorrelation amplitude and shortest pulse duration always coincide. Therefore, the optics of the imaging system can be first adjusted to obtain the minimum autocorrelation duration and then the wavefront of incident light modified to maximise the autocorrelation intensity, iterating this procedure until the positions of minimum pulse duration and maximum autocorrelation amplitude coincide

Active Localization of Gas Leaks using Fluid Simulation

Sensors are routinely mounted on robots to acquire various forms of measurements in spatio-temporal fields. Locating features within these fields and reconstruction (mapping) of the dense fields can be challenging in resource-constrained situations, such as when trying to locate the source of a gas leak from a small number of measurements. In such cases, a model of the underlying complex dynamics can be exploited to discover informative paths within the field. We use a fluid simulator as a model, to guide inference for the location of a gas leak. We perform localization via minimization of the discrepancy between observed measurements and gas concentrations predicted by the simulator. Our method is able to account for dynamically varying parameters of wind flow (e.g., direction and strength), and its effects on the observed distribution of gas. We develop algorithms for off-line inference as well as for on-line path discovery via active sensing. We demonstrate the efficiency, accuracy and versatility of our algorithm using experiments with a physical robot conducted in outdoor environments. We deploy an unmanned air vehicle (UAV) mounted with a CO2 sensor to automatically seek out a gas cylinder emitting CO2 via a nozzle. We evaluate the accuracy of our algorithm by measuring the error in the inferred location of the nozzle, based on which we show that our proposed approach is competitive with respect to state of the art baselines.Comment: Accepted as a journal paper at IEEE Robotics and Automation Letters (RA-L

Primed CRISPR adaptation in Escherichia coli cells does not depend on conformational changes in the Cascade effector complex detected in vitro

Skoltech Ph.D. program in the Life Sciences (to A.K.); European Research Council consolidator grant [GA 724863 to R.S].; NIH [R01 GM10407] and Russian Science Foundation [14-14-00988] grants to K.S.; UMNIK grant 8115GU/2015 to O.M., and institutional support from Skoltech to K.S. Funding for open access charge: Skolkovo Institute of Science and Technology internal funding.In type I CRISPR-Cas systems, primed adaptation of new spacers into CRISPR arrays occurs when the effector Cascade-crRNA complex recognizes imperfectly matched targets that are not subject to efficient CRISPR interference. Thus, primed adaptation allows cells to acquire additional protection against mobile genetic elements that managed to escape interference. Biochemical and biophysical studies suggested that Cascade-crRNA complexes formed on fully matching targets (subject to efficient interference) and on partially mismatched targets that promote primed adaption are structurally different. Here, we probed Escherichia coli Cascade-crRNA complexes bound to matched and mismatched DNA targets using a magnetic tweezers assay. Significant differences in complex stabilities were observed consistent with the presence of at least two distinct conformations. Surprisingly, in vivo analysis demonstrated that all mismatched targets stimulated robust primed adaptation irrespective of conformational states observed in vitro. Our results suggest that primed adaptation is a direct consequence of a reduced interference efficiency and/or rate and is not a consequence of distinct effector complex conformations on target DNA.Publisher PDFPeer reviewe

Reflecting the past, imag(in)ing the past: macro-reflection imaging of painting materials by fast MIR hyperspectral analysis

Imaging spectroscopy has been developed in the last two decades in the visible and infrared spectral range for detecting pigments and binders on paintings. The near-infrared (NIR) region has been proved effective for the discrimination of lipids and proteinaceous binders. More recently, the mid-infrared (MIR) range has also been tested on paintings. Reflection imaging prototypes already developed could be further optimized for cultural heritage analysis, for example by: enhancing the instrument configuration and performance; adopting compressive strategies to increase data processing speeds; using data validation to confirm that the processed image reflects the composition of a painted surface; and lowering price to enable more cost-effective analysis of large surface areas. Here, we demonstrate a novel hyperspectral Fourier transform spectrometer (HS FTS), which enables an imaging strategy that provides a significant improvement in acquisition rate compared to other state-of-the-art techniques. We demonstrate hyperspectral imaging across the 1400–700 cm−1 region in reflection mode with test samples and the painting ‘Uplands in Lorne’ (Acc. No.: GLAHA43427) by D.Y. Cameron (1865–1945). A post-processing analysis of the resulting hyperspectral images, after validation of reference samples by conventional Fourier transform infrared spectroscopy, shows the potential of the method for efficient non-destructive classification of different materials found on painted cultural heritage. This research demonstrates that the HS FTS is a convenient and compact tool for non-invasive analysis of painted cultural heritage objects at spatio-spectral acquisition rates potentially higher than current FTS imaging techniques. Ultimately, when combined with fast graphics processing unit-based reconstruction, the HS FTS may enable fast, large area imaging