Laser-free Ultrafast Tunable Stroboscopic TEM imaging for Biomedical Applications

Project Summary Abstract Major advances in cell biology and biomedical research are tightly linked to innovations in microscopyIn the modern eramany breakthroughs rely on understanding and visualizing complex molecular structuresnot only in their static states but also as a function of timeThe development of ultrafast electron transmission microscopyUTEMand variant techniques now allows scientists to record dynamic processes with spatial and temporal resolutions down to sub angstrom and the femtosecond levelsThe combination of such resolutions opens to investigation myriad fundamentalatomic scale processes in biology and other fieldsIn structural biology applicationsthe fundamental limitation is electron beam radiation damageThere have been various strategies to keep it at a minimal levelMany of them rely on the minimization of the electron dose exposure that inevitably increase the image acquisition time required for accumulating signal to the acceptable contrastThe acquisition time in available laser based UTEMs is governed by laser repetition rate and usually less than one MHzAt the momentno timeresolved techniques are able to provide GHz scale or higher sampling ratesIn additioncontemporary UTEMs require substantial modification of existing TEM system with exorbitant costly femtosecond laser equipmentThe necessity to both own and operate a non standard electron microscope and an ultrafast laser system limits the technology to only a few research groups in the worldEuclid Beamlabs proposes to develop a novel retrofittable into standard TEM laser free GHz tunable stroboscopic assembly that can enable an ordinaryto operate in an entirely different stroboscopic mode producing time resolved data at picosecond time intervals and GHz sampling ratesat subnano scale spatial resolutionand to provide high contrast imagingOur approach replaces the expensive fs laser system with an electromagnetic mechanical pulserEMMPa specially designed cavity commonly used in the beam physics community for particle accelerationIn the family of time resolved electron probe methodssuch laser free GHz stroboscopic concept would fulfill a different temporal landscape that is complementary to the existing commercial solutionsThe technology will preserve the default TEM thermionic field emission electron source providing stable highly coherent illumination with high contrast imaging for biological objects with reduced radiation damaging effectsThe fastermore thantimesrepetition rate will also allow unprecedented image acquisition speed that significantly increases experiment throughputThe whole userfriendly retrofittable assembly that includes EMMPRF sourceand synchronization systemwill be compatible with commercial TEM platformsIt will significantly reduce the price for a UTEM system making it affordable for the larger scientific communityIn Phasewe will design the assembly for available JEOL TEM with specific goal of maximal contrast for imaging biologicaland carry out the first testing experiment as well Project Narrative This project is designed to deliver a truly novel and advanced stroboscopic technology on a transmission electron microscopeTEMplatform that will providemolecular video electron microscopyand will help to answer many new questions on dynamics and functioning biomacromoleculesIn the family of timeresolved electron probe methodssuch laser free GHz stroboscopic concept will fulfill a different temporal landscape that is complementary to the existing solutionsA novel technology will be retrofittable into commercial TEMswill cost significantly lower due to absence of expensive laser systemand will havefaster image acquisition speed