Design and testing of a high accuracy robotic single-cell manipulator

Abstract

We have designed, built and tested a high accuracy robotic single-cell manipulator to be able to pick individual cells from array of microwells, each 30 Pm or 50 pm cubed. Design efforts have been made for higher accuracy, higher throughput, and compactness. The proposed system is designed to have a T-drive mechanism with two linear stages for XY-plane positioning to have higher stiffness and less structurally inherent error. Precision is especially required in Z-axis movement for successful cell-retrieval procedure and so a rotational mechanism with a voice coil actuator, among many options, is selected for the Z-axis motion because this results in relatively smaller reaction on the system and has advantages of direct drive. The prototype of the robotic single-cell picker integrates the Z-axis and XY stage motion, realtime microscopy imaging, and cell manipulation with a NI PXI-controller centered as a main real-time controller. This prototype is built to test performances of the proposed system in terms of single-cell retrieval and this thesis also discusses the experiments for the cell-retrieval process with microbeads of the equivalent size and the results as well. This proposed system will be used to help select and isolate an individual hybridoma from polyclonal mixture of cells producing various types of antibodies. It is important to be able to do this cell-retrieval task since a single isolated hybridoma cell produces monoclonal antibody that only recognizes specific antigens, and this monoclonal antibody can be used to develop cures and treatments for many diseases. Our research's development of accurate and dedicated mechatronics solution will contribute to more rapid and reliable investigation of cell properties. Such analysis techniques will act as catalyst for quicker discovery of treatments and vaccines on a wide range of diseases including HIV infection, tuberculosis, hepatitis C, and malaria with potential impact on the society.