In the future, the precision manipulation of small objects will become more and more important for appliances such as data storage, micro assembly, sample manipulation in microscopes, cell manipulation, and manipulation of beam paths by micro mirrors. At the same time, there is a drive towards miniaturized systems. Therefore, Micro ElectroMechanical Systems (MEMS), a fabrication technique enabling micron sized features, has been researched for precision manipulation. MEMS devices comprise micro sensors, actuators, mechanisms, optics and fluidic systems. They have the ability to integrate several functions in a small package. MEMS can be commercially attractive by providing cost reduction or enabling new functionality with respect to macro systems. Combining design principles, a mature design philosophy for creating precision machines, and MEMS fabrication, a technology for miniaturization, could lead to micro systems with deterministic behavior and accurate positioning capability. However, in MEMS design trade-offs need to be made between fabrication complexity and design principle requirements. Therefore, the goal of this research has been twofold: 1. Design and manufacture a 6 Degrees-of-Freedom (DOFs) MEMS-based manipulator with nanometer resolution positioning. 2. Derive principle solutions for the synthesis of exact kinematic constraint design and MEMS fabrication technology for multi DOFs precision manipulation in the micro domain. The Transmission Electron Microscope (TEM) sample manipulator has been used as a suitable carrier for the project. Design principles which are relevant to MEMS in particular, such as exact kinematic constraint design, and using compliant mechanisms to avoid backlash, play, friction, wear and hysteresis, have been studied. Special attention has been given to leaf-spring stiffness reduction due to large deflections. This was essential because deflections of compliant mechanisms in MEMS are relatively large and often feature leaf-springs as elastic elements. Designs have been presented for improved straight guiding with respect to the traditional folded flexure. This is important for the performance of electrostatic comb-drive actuators. For the 6 DOFs motion of the manipulator, the necessary combination of in- and out-of-plane motion of the wafer in MEMS is rather new. A motion converting mechanism using only one type of actuator has been chosen in favor of a combination of in- and out-of-plane actuators. Six electrostatic comb-drives have been used for actuation. The manipulator is a parallel kinematic mechanism. Based on these system design choices, three concepts have been presented and evaluated. Each concept includes a fabrication process in conjunction with an exact kinematic constraint design. The specifications for a precision manipulator require high frequency vibration modes combined with compliant actuation modes. The compliant actuation modes are necessary to generate sufficient displacement of +/- 10 μm by the low force MEMS actuators. Therefore, the design principles, especially exact kinematic constraint design, have been applied as much as possible. However, trade-offs had to be made between what is required from an exact kinematic constraint design point of view and what is feasible with the available fabrication processes. Therefore, to determine flexure dimensions, the used flexure mechanisms have been modeled taking into account geometric non-linearities. Although the design incorporates relatively long and slender leaf-springs, the first vibration mode frequency is 3.8 kHz (with blocked actuators). However, the clean room fabrication of the total manipulator required more time than available during the project. Therefore, only several fabrication steps of the manipulator design have been tested. A 3 mask step fabrication process of the clamping mechanism based on the 5 mask step process of the 6 DOFs manipulator served as a test case for the fabrication. A clamping mechanism with a locking device enhances the passive stability of the manipulator by unpowered clamping of the manipulator actuators once the manipulator has reached its targeted position. The cross-talk between the electronbeam of the TEM and electric fields from the actuators of the manipulator is also decreased. Additionally, by using a clamping mechanism, the manipulator can be switched between compliant actuation modes for positioning, and high frequency vibration modes during imaging. The precision MEMS-based clamping mechanism for a relatively large force (0.5 mN) was developed, fabricated and characterized. The elastic deformation of the clamp flexures was optimized so as not to influence the position of the TEM sample manipulator. The device area of the total mechanism was further optimized by balancing the area necessary for sufficient flexure compliance in the actuation direction and the actuator area necessary for sufficient actuation force and stroke. Measurements showed that the clamping mechanism is able to fix a test actuator, hold it without power, and release it.