Cell Manipulation System Based on a Self-Calibrating Silicon Micro Force Sensor Providing Capillary Status Monitoring

Abstract

In this paper, a system for cell manipulation is presented. A two axis stage is arranged on an inverted microscope to place cells in focus. Cell manipulation can thereby be observed while the system automatically runs force controlled measurements. A high precision linear motor moves a force sensor, which has been equipped with a stimulation tool, e.g., a micro capillary for cell injection. The sensor is made up of silicon and consists of a membrane with a boss structure, which enables measurements as low as 120 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu{\rm N}$</tex></formula> . For the first tests, an injection capillary is mounted on the topside, while the backside is fixed to a printed circuit board with an integrated air pressure connection. Air pressure was applied under the membrane because the glass capillaries with outer diameters of at least 1 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu{\rm m}$</tex></formula> do not allow calibration via other force sensors. This setup provides a self-calibration of the mounted sensor system, before the measurements of the occurred forces on the cells during the penetration of the capillary. Using the 3-D force measurement capability of the sensor, the system features a unique end-effector status monitoring.