Robotic fluidic jet for automated cellular and intracellular mechanical characterization

In mammalian embryo development, the first cell lineage differentiation produces an inner cell mass and trophoblasts. Although it was speculated in biology that mechanical forces facilitate the first cell lineage differentiation, due to the natural physical barrier formed by the zona pellucida (i.e., outer membrane of an embryo), there is no technology for directly measuring the mechanical properties of the inner cell mass and trophoblasts inside the embryo. This paper reports a robotic fluidic jet system that enables mechanical characterization of intra-embryonic structures. The system accurately positions the fluidic jet to the target cell in 3D, based on visual servo control with a contact detection algorithm and a focus adjustment method. Under forces generated by the fluidic jet, the cell is deformed and cell deformation is measured with a sub-pixel contour detection algorithm. The fluidic jet system is capable of applying forces up to 50 nN with a resolution of 10 pN and measuring cell deformation with a sub-pixel resolution. In validation experiments, the system was used to measure the mechanical properties of two types of cancer cell lines. The results showed higher grade of cancer cells has lower stiffness. Further experiments performed inside mouse embryos, for the first time, revealed a significant difference in Young's modulus between the inner cell mass and trophoblasts (3.5 ± 0.72 kPa vs. 4.7 ± 0.65 kPa).