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Macromolecular Femtosecond Crystallography
The Macromolecular Femtosecond Crystallography (MFX) instrument makes use of the unique brilliant hard X-ray pulses from LCLS to perform a wide variety of experiments utilizing various techniques. The primary capability of MFX is to make use of the high peak power of the focused x-ray beam using the “diffraction-before-destruction” method. This technique prevents damage to a sample during the measurement by performing the measurement faster than the damage or destruction process with ultrashort pulses. This is particular advantageous for biological samples that suffer from electronic and structural damage during long continuous exposures to x-rays. The MFX instrument will make use of well-developed crystallographic techniques from synchrotrons and from the early days of LCLS to provide an atmospheric pressure, dedicated yet versatile instrument for crystallographic measurements at LCLS.
MFX will consist of a flexible instrumentation suite to make use of hard x-rays primarily in an atmospheric pressure environment. It will enable femtosecond crystallography measurements capable of determining the structure of biomolecules using crystals. Other techniques such as X-ray Emission Spectroscopy, back-scattering, small and wide angle scattering will also be compatible with the MFX system.
Plans exist for a flexible pump laser system for time-resolved experiments in the femtosecond time scale. MFX will be available for any scientific field requiring use of the LCLS beam, including structural biology, material science, materials in extreme conditions, atomic molecular and optical physics, chemistry and soft condensed matter, provided MFX is deemed most suitable for a particular science case. Samples can be introduced to the x-ray beam either fixed on targets using a high speed and high precision goniometer or using liquid jet systems that can deliver samples to the beam. Beryllium compound refractive lenses will be used for focusing the x-ray beam and control the spot size at the sample. The MFX instrument will operate primarily in the 5-20 keV range with the lower limit set by the atmospheric pressure operation and the upper limit eventually set by the capabilities of LCLS-II.
X-ray diffraction has long been used to determine atomic structures of biomolecules. Unfortunately, the same x-rays that are used to probe the structure of the sample also get absorbed and deposit energy in the sample, causing irreparable damage. This often limits the resolution achievable in a particular sample, especially biological samples which are particularly sensitive to damage. X-ray crystallography has beam very successful studying biological samples by spreading the damage over as many as billions of molecules in a single crystal, greatly enhancing the diffraction signal. Since the molecules are all identical and precisely aligned in the crystal, the X-ray scattering information is preserved and the structure can be determined. As crystals are reduced in size, they become more sensitive to damage due to the need to irradiate every molecule with more x-rays to get a measurable signal, causing more damage for each molecule.
LCLS offers a way around the damage problem. Since X-ray pulses from LCLS are very intense and very short, it is possible to deliver a higher dose to a sample and record the scattered X-ray information before the damage processes have time to destroy the sample. In other words, an LCLS X-ray pulse can be focused onto a sample, which gets destroyed – but not before the scattered X-rays are already on their way to the detector carrying the information needed to deduce the structure of the molecule. The Macromolecular Femtosecond Crystallography (MFX) instrument offers the possibility of determining structures at resolution beyond the damage limit for samples which are limited by radiation damage at synchrotron sources.
MFX aims to provide a flexible suite of instrumentation for “diffract-before-destroy” studies in structural biology in an atmospheric pressure sample environment. In time, this will be complemented with other tools, such as a pump laser, to make MFX a highly versatile system capable of a variety of scattering and spectroscopy techniques. Scientific fields such as material science, materials in extreme conditions, chemistry and soft condensed matter will find applications at MFX.
The high flux of LCLS also has the advantage of allowing in principle damage-free higher resolution measurements of radiation-sensitive samples such as metalloenzymes. A series of crystals can be illuminated by LCLS X-ray pulses and the diffraction patterns recorded. A full 3D set similar to conventional protein crystallography can be assembled from many crystals or many shots on the same large crystal and yield the protein structure. The crystals can be delivered into the MFX beam mounted on a goniometer system (Cohen et al, PNAS (2014)) or using a liquid jet (Weierstall et al, Rev. Sci. Instrum. (2010)), LCP jet (Weierstall et al, Nature Communications (2014)), an electrospinning jet (Sierra et al, Acta Cryst D (2012)).
Small angle scattering measurements at atmospheric pressure will be enabled by MFX. The eventual addition of a pump laser system will enable time-resolved measurements to study ultrafast dynamics in biological samples (Levantino et al, Nature Comm (2015)).
SLAC National Accelerator Laboratory, Menlo Park, CA
Operated by Stanford University for the U.S. Dept. of Energy