With a three-dimensional (3D) momentum imaging technique, we investigated the laser desorption ionization dynamics initiated by both chirped picosecond and femtosecond pulses. 3D momentum images of desorbed ions from 2,5-dihydroxybenzoic acid (DHB), a common laser desorption matrix, were obtained for the first time. A striking difference was observed between the processes initiated by femtosecond and picosecond pulses. The lack of initial momentum in ions produced by femtosecond pulses suggests a suppression of plume formation, which can be exploited to increase the sensitivity of matrixassisted laser desorption ionization.

A camera-based three-dimensional (3D) imaging system with a superb time-of-flight (TOF) resolution and multi-hit capability was recently developed for electron/ion imaging [Lee et al. J. Chem. Phys. 141, 221101 (2014)]. In this work, we report further improvement of the event rate of the system by adopting an event-driven camera, Tpx3Cam, for detecting the 2D positions of electrons, while a high-speed digitizer provides highly accurate (˜30 ps) TOF information for each event at a rate approaching 1 Mhits/sec.

No abstract

Achromatopsia is an inherited retinal disorder of cone photoreceptors characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. Approximately 50% of cases are caused by mutations in the cone photoreceptor-specific cyclic nucleotide gated channel beta subunit (CNGB3) gene. Studies in CNGB3-mutant dogs showed that subretinal injection of an AAV vector expressing human CNGB3, which has 76% amino acid identity with canine CNGB3, driven by a 2.1 kb human red cone opsin promoter (PR2.1) and packaged in AAV5 capsids (AAV5-PR2.1-hCNGB3) rescued cone photoreceptor function, but at high doses was associated with an inflammatory response (focal chorioretinitis) consistent with immune-mediated toxicity. AAV vectors containing the PR2.1 promoter packaged in AAV5 capsids and expressing either the native canine CNGB3 (AAV5-PR2.1-cCNGB3) or the human CNGB3 (AAV5-PR2.1-hCNGB3) were evaluated at different dose levels in CNGB3-mutant dogs. The vector expressing canine CNGB3 achieved somewhat better rescue of cone function but unexpectedly was associated with a greater degree of retinal toxicity than the vector expressing human CNGB3. Very low-level T-cell immune responses to some AAV or CNGB3 peptides were observed in animals that received the higher vector dose. There was a more than twofold increase in serum neutralizing antibodies to AAV in one of three animals in the low-dose group and in two of three animals in the high-dose group. No serum anti-hCNGB3 antibodies were detected in any animal. The results of this study do not support the hypothesis that the focal chorioretinitis seen with high doses of AAV5-PR2.1-hCNGB3 in the initial studies was due to an immune response to human CNGB3.

We report a new implementation of three-dimensional (3D) momentum imaging for electrons, employing a two-dimensional (2D) imaging detector and a silicon photomultiplier tube (siPMT). To achieve the necessary time resolution for 3D electron imaging, a poly(p-phenylene)-dye-based fast scintillator (Exalite 404) was used in the imaging detector instead of conventional phosphors. The system demonstrated an electron time-of-flight resolution comparable with that of electrical MCP pick-off (tens of picoseconds), while achieving an unprecedented dead time reduction (∼0.48 ns) when detecting two electrons.