Automatic Stiffness Measurement of Small Objects Using an Integrated System of Simultaneous Multi-scale Observation and Two-Directional Force Measurement

Recently, the field of life sciences has witnessed significant advancements, leading to the exploration of various cell characteristics to evaluate cellular behavior. Among these characteristics, cell stiffness has garnered considerable attention. It is widely acknowledged that cell stiffness undergoes changes based on the cell's physiological state, rendering stiffness measurement a critical parameter in cell evaluation. However, the extensive research into cell stiffness has been hindered by the challenges associated with manipulating micron-scale cells and measuring nano-scale forces. Previous studies have proposed a cell stiffness measurement system utilizing a two-fingered microhand equipped with a micro force sensor. Nonetheless, this approach required manual manipulation of the target object, resulting in potential errors in stiffness measurement. Additionally, manual manipulation restricted the workspace, limiting its applicability. To address these limitations, this paper introduces an automated stiffness measurement technique that integrates force data and image data. Furthermore, a multi-scale simultaneous observation system is presented, combining optical systems from two microscopes with different magnification levels.