Leonardo Sala

Bio: Leonardo Sala is an academic researcher from Paul Scherrer Institute. The author has contributed to research in topics: Femtosecond & Laser. The author has an hindex of 10, co-authored 18 publications receiving 554 citations.

SwissFEL: The Swiss X-ray Free Electron Laser

Abstract: The SwissFEL X-ray Free Electron Laser (XFEL) facility started construction at the Paul Scherrer Institute (Villigen, Switzerland) in 2013 and will be ready to accept its first users in 2018 on the Aramis hard X-ray branch. In the following sections we will summarize the various aspects of the project, including the design of the soft and hard X-ray branches of the accelerator, the results of SwissFEL performance simulations, details of the photon beamlines and experimental stations, and our first commissioning results.

A compact and cost-effective hard X-ray free-electron laser driven by a high-brightness and low-energy electron beam

Abstract: We present the first lasing results of SwissFEL, a hard X-ray free-electron laser (FEL) that recently came into operation at the Paul Scherrer Institute in Switzerland. SwissFEL is a very stable, compact and cost-effective X-ray FEL facility driven by a low-energy and ultra-low-emittance electron beam travelling through short-period undulators. It delivers stable hard X-ray FEL radiation at 1-A wavelength with pulse energies of more than 500 μJ, pulse durations of ~30 fs (root mean square) and spectral bandwidth below the per-mil level. Using special configurations, we have produced pulses shorter than 1 fs and, in a different set-up, broadband radiation with an unprecedented bandwidth of ~2%. The extremely small emittance demonstrated at SwissFEL paves the way for even more compact and affordable hard X-ray FELs, potentially boosting the number of facilities worldwide and thereby expanding the population of the scientific community that has access to X-ray FEL radiation. The first lasing results at SwissFEL, an X-ray free-electron laser, are presented, highlighting the facility’s unique capabilities. A general comparison to other major facilities is also provided.

GigaFRoST: the gigabit fast readout system for tomography

Abstract: Owing to recent developments in CMOS technology, it is now possible to exploit tomographic microscopy at third-generation synchrotron facilities with unprecedented speeds. Despite this rapid technical progress, one crucial limitation for the investigation of realistic dynamic systems has remained: a generally short total acquisition time at high frame rates due to the limited internal memory of available detectors. To address and solve this shortcoming, a new detection and readout system, coined GigaFRoST, has been developed based on a commercial CMOS sensor, acquiring and streaming data continuously at 7.7 GB s−1 directly to a dedicated backend server. This architecture allows for dynamic data pre-processing as well as data reduction, an increasingly indispensable step considering the vast amounts of data acquired in typical fast tomographic experiments at synchrotron beamlines (up to several tens of TByte per day of raw data).

Towards on-the-fly data post-processing for real-time tomographic imaging at TOMCAT.

Abstract: Sub-second full-field tomographic microscopy at third-generation synchrotron sources is a reality, opening up new possibilities for the study of dynamic systems in different fields. Sustained elevated data rates of multiple GB/s in tomographic experiments will become even more common at diffraction-limited storage rings, coming in operation soon. The computational tools necessary for the post-processing of raw tomographic projections have generally not experienced the same efficiency increase as the experimental facilities, hindering optimal exploitation of this new potential. We present here a fast, flexible, and user-friendly post-processing pipeline overcoming this efficiency mismatch and delivering reconstructed tomographic datasets just few seconds after the data have been acquired, enabling fast parameter and image quality evaluation as well as efficient post-processing of TBs of tomographic data. With this new tool, also able to accept a stream of data directly from a detector, few selected tomographic slices are available in less than half a second, providing advanced previewing capabilities paving the way to new concepts for on-the-fly control of dynamic experiments.

Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography

Abstract: Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 A resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1 ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1 mg per collected time point. Accumulation of M intermediate within the crystal lattice is confirmed by time-resolved visible absorption spectroscopy. This study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX. Serial femtosecond crystallography using X-ray free-electron lasers has huge potential for time-resolved structural experiments. Here, the authors present a structure of the light-driven proton pump bacteriorhodopsin using these techniques.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

A three-dimensional movie of structural changes in bacteriorhodopsin

Abstract: Bacteriorhodopsin (bR) is a light-driven proton pump and a model membrane transport protein. We used time-resolved serial femtosecond crystallography at an x-ray free electron laser to visualize conformational changes in bR from nanoseconds to milliseconds following photoactivation. An initially twisted retinal chromophore displaces a conserved tryptophan residue of transmembrane helix F on the cytoplasmic side of the protein while dislodging a key water molecule on the extracellular side. The resulting cascade of structural changes throughout the protein shows how motions are choreographed as bR transports protons uphill against a transmembrane concentration gradient.

SwissFEL: The Swiss X-ray Free Electron Laser

Abstract: The SwissFEL X-ray Free Electron Laser (XFEL) facility started construction at the Paul Scherrer Institute (Villigen, Switzerland) in 2013 and will be ready to accept its first users in 2018 on the Aramis hard X-ray branch. In the following sections we will summarize the various aspects of the project, including the design of the soft and hard X-ray branches of the accelerator, the results of SwissFEL performance simulations, details of the photon beamlines and experimental stations, and our first commissioning results.

Opportunities and Challenges for Biosensors and Nanoscale Analytical Tools for Pandemics: COVID-19.

Abstract: Biosensors and nanoscale analytical tools have shown huge growth in literature in the past 20 years, with a large number of reports on the topic of 'ultrasensitive', 'cost-effective', and 'early detection' tools with a potential of 'mass-production' cited on the web of science Yet none of these tools are commercially available in the market or practically viable for mass production and use in pandemic diseases such as coronavirus disease 2019 (COVID-19) In this context, we review the technological challenges and opportunities of current bio/chemical sensors and analytical tools by critically analyzing the bottlenecks which have hindered the implementation of advanced sensing technologies in pandemic diseases We also describe in brief COVID-19 by comparing it with other pandemic strains such as that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for the identification of features that enable biosensing Moreover, we discuss visualization and characterization tools that can potentially be used not only for sensing applications but also to assist in speeding up the drug discovery and vaccine development process Furthermore, we discuss the emerging monitoring mechanism, namely wastewater-based epidemiology, for early warning of the outbreak, focusing on sensors for rapid and on-site analysis of SARS-CoV2 in sewage To conclude, we provide holistic insights into challenges associated with the quick translation of sensing technologies, policies, ethical issues, technology adoption, and an overall outlook of the role of the sensing technologies in pandemics

Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser

Abstract: Ultrafast isomerization of retinal is the primary step in photoresponsive biological functions including vision in humans and ion transport across bacterial membranes. We used an x-ray laser to study the subpicosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin. A series of structural snapshots with near-atomic spatial resolution and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket before passing through a twisted geometry and emerging in the 13-cis conformation. Our findings suggest ultrafast collective motions of aspartic acid residues and functional water molecules in the proximity of the retinal Schiff base as a key facet of this stereoselective and efficient photochemical reaction.