Tapered image charge detector for measuring velocity distributions of submicrometer particle scattering.

A novel detector for measuring the post-impact velocities (trajectory and speed) of charged submicrometer particles is presented. A stack of tapered cylindrically symmetric electrodes connected to a set of image charge detection circuits is used in conjunction with an image-charge-sensitive target to measure the incident velocity and scattered trajectories of charged particles following impact with the target. This particle detector is used in conjunction with a mass, charge, and energy-selected source of collimated charged particles. Polystyrene latex spheres were used to characterize the performance of the detector, and examples of scattering trajectories are analyzed to demonstrate detector functionality. Measurements of the coefficient of restitution for 500 nm diameter tin particles are also reported and compared with previous measurements performed with a simpler image-charge detector. Finally, the angular distribution for 500 nm tin particles scattering from highly polished molybdenum at an incident velocity of 150 m/s is reported.

A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum.

Infection by Plasmodium falciparum is the leading cause of malaria in humans. The parasite contains a unique and essential plastid-like organelle called the apicoplast that, similar to the mitochondria and chloroplast, houses its own genome that must undergo replication and repair. The putative apicoplast replicative DNA polymerase, POM1, has no direct orthologs in mammals, making the P. falciparum POM1 an attractive antimalarial drug target. Here, we report on a fluorescent high-throughput DNA polymerase assay that relies on the ability of POM1 to perform strand-displacement synthesis through the stem of a DNA hairpin substrate, thereby separating a Cy3 dye from a quencher. Assay-validation experiments were performed using 384-well plates and resulted in a signal window of 7.90 and aZ' factor of 0.71. A pilot screen of a 2880-compound library identified 62 possible inhibitors that cause more than 50% inhibition of polymerase activity. The simplicity and statistical robustness of the assay suggest it is well suited for the screening of novel apicoplast polymerase inhibitors that may serve as lead compounds in antimalarial drug-discovery efforts.