Novel particle manipulation techniques are developed to separate, isolate, and control a wide range biomolecules from DNA to cells in complex solution such as whole blood. First, we show that integrating an insulating tip with dielectrophoresis allows us to trap, carry, reposition, and relocate nanoscale objects, which can be used as molecular tweezers without fouling, electrolysis, and joule heating issues associated with conventional dielectrophoretic methods. In addition, we find that two theoretical force calculations (Clausius-Mossotti model and counter ion fluctuation model) result in a factor of 2-40 difference, but the magnitude of both is 4 orders stronger than the thermal force, which is strong enough to manipulate objects in the medium. Second, we perform sedimentation and size-based particle separation methods in a microfluidic device configuration. Using polydimethylsiloxane and its high gas solubility, we demonstrate a sedimentation-based, blood cell separation method. To further isolate small biomarkers such as exosomes utilizing a deterministic lateral displacement principle, we fabricate nanoscale pillar structures on a silicon wafer using multiple nanolithography processes and explore possibilities for size-dependent particle separation on the device.