Reducing Radiation Damage in Soft Matter with Femtosecond Timed Single-Electron Packets

Abstract

Despite development of myriad mitigation methods, radiation damage continues to be a major limiting factor in transmission electron microscopy. Intriguing results have been reported using pulsed-laser driven and chopped electron beams for modulated dose delivery, but 10 the underlying relationships and effects remain unclear. Indeed, delivering precisely-timed single-electron packets to the specimen has yet to be systematically explored, and no direct comparisons to conventional methods within a common parameter space have been made. Here, using a model linear saturated hydrocarbon (n-hexatriacontane, C 36 H 74 ), we show that preciselytimed delivery of each electron to the specimen, with a well-defined and uniform time between 15 arrival, leads to a repeatable reduction in damage compared to conventional ultralow-dose methods for the same dose rate and the same accumulated dose. Using a femtosecond pulsed laser to confine the probability of electron emission to a 300-fs temporal window, we find damage to be sensitively dependent on the time between electron arrival (controlled with the laser repetition rate) and on the number of electrons per packet (controlled with the laser-pulse 20 energy). Relative arrival times of 5, 20, and 100 µs were tested for electron packets comprised of, on average, 1, 5, and 20 electrons. In general, damage increased with decreasing time between electrons and, more substantially, with increasing electron number. Further, we find that improvements relative to conventional methods vanish once a threshold number of electrons per packet is reached. The results indicate that precise electron-by-electron dose delivery leads 25 to a repeatable reduction in irreversible structural damage, and the systematic studies indicate this arises from control of the time between sequential electrons arriving within the same damage radius, all else being equal.

Mitigation of radiation damage in biological macromolecules via tunable picosecond pulsed transmission electron microscopy

“…Table 1 shows that the critical dose using 300 keV varies between 571 and 1124 e − •nm −2 , for 100% and 10% duty cycles, respectively. This factor of 2 is comparable to the 1.8x dose rate improvement in the paraffin fading curve reported by University of Minnesota for 200 keV laser-generated single-electron packets 14 .…”

“…Critical dose for pulsed beam improves by a factor of up to 2 at room temperature compared with the continuous random beam for constant dose rate (electron flux). This factor of 2 exceeds laser-based mitigation efforts recently reported at 200 kHz in paraffin 14 , and at a remarkable~100 MHz average single-electron repetition rate, leading to orders of magnitude faster data acquisition on a highly tunable system.…”

“…In this section we assess pulse-dependent critical dose at 5. 14 . But the GHz RF pulser can access the same time-structured single-electron regime -and the same damage mitigation -as the laser pulser at much higher repetition rates with orders of magnitude faster acquisition.…”

“…(b) 40 MHz -6 GHz RF drives K1 (and K2 with 180º phase delay) to sweep beam across the chopper aperture, then demodulate transverse momentum. (c) Adapted from 14 : beam has continuous or pulsed mode; electrons are gated, gate width and frequency are tunable. Detector exposure ( time to acquire a single diffraction pattern image) averages across millions of gate periods (not to scale).…”

“…Until recently, critical dose was not thought to depend on how quickly the dose was applied. However, several groups have now reported mitigation of radiation damage via ultrafast electron pulses [14][15][16][17] . These groups used either laser-driven ultrafast electron pulses with kHz to MHz repetition rate, or a pulsed beam of fixed repetition rate produced by GHz radiofrequency (RF) deflecting cavities.…”