Systems and methods of manipulating nano- and micrometer scale particles are described. The system generally includes an optical imaging system for acquiring an image of a sample of particles, a processor for analyzing the image, identifying a target particle in the image, and determining the lateral position of the target particle in the sample of particles; and a vacuum-based probe system including a moveable probe and a vacuum pump configured to apply a vacuum up through the probe. The processor provides instructions for moving the probe to the lateral position of the target particle, and instructions to apply a vacuum up through the probe such that the target particle is pulled away from the sample of particles and held against the tip of the moveable probe. Once the probe collects and holds a target particle against the tip thereof, the probe can be moved to relocated the target particle to a precise new location, such as on to a particle retrieval tray.