Microrobotics for Molecular Biology - Manipulating Deformable Objects at the Microscale
Introduction
Intelligent microrobotic systems have the potential to change the way in which biological cells are studied and manipulated by enabling complex biomanipulation techniques. From a robotics standpoint, the manipulation of biological cells and materials presents several interesting research issues that extend well beyond biomanipulation. Biological structures are usually highly deformable objects, and the material properties of these objects are often not well quantified, so developing strategies for manipulating deformable objects must be addressed. Most biological cells are between 1 and 100 microns in diameter, depending on the cell type, so micromanipulation issues must be explored, including the appropriate use of high resolution, low depth-of-field vision feedback and very low magnitude force feedback. Although multi-axis force sensing capabilities would be useful for handling cells by providing information on injection forces as well as tangential forces generated by improperly aligned cell probes, sensors capable of multi-axis force sensing at the force scales required are currently unavailable. Robotic devices capable of complex manipulation of biological cells and materials are only beginning to emerge, and robotic systems capable of integrating a variety of novel sensory information for biomanipulation are still very much an open research topic. By pursing robotic manipulation of small-scale biological structures, many interesting robotics research avenues such as micromanipulation, deformable object handling, multi-sensor integration, and force and vision feedback assimilation must be explored.
Autonomous Microrobotic Cell Injection
Our preliminary attempt to understand micromanipulation issues with manipulating biological cells was the development of a microrobotic cell injection system.
In the autonomous embryo pronuclei DNA injection system shown in Figure 1, visual servoing and precision motion control are combined in a hybrid control scheme. Experimental results demonstrate that the success rate for automatic injection is 100%. The time required to perform the injections is comparable with manual operation by a proficient technician.
Multi-Axis MEMS Cellular Force Sensor
Despite the high success rate of the automatic microrobotic cell injection, it is apparent that force feedback could improve the cycle time of the process, increase robustness further, and help quantify biomembrane mechanical properties that are necessary for vision and force assimilation.
The MEMS-based two-axis cellular force sensor shown in Figure 2 is capable of resolving normal forces applied to a cell as well as tangential forces generated by improperly aligned cell probes. A high-yield microfabrication process was developed to form the 3-D high aspect ratio structure by using Deep Reactive Ion Etching (DRIE) on Silicon-On-Insulator (SOI) wafers. The cellular force sensors are capable of resolving forces as low as 0.01 microNewton.
Vision-Based Biomembrane Force Estimation
The multi-axis MEMS force sensors have been used for biomembrane force measurements and biomembrane mechanical property determination. Biomembrane mechanical models have been established.
A visual tracking algorithm for deformable contour tracking using physics-based models has been proposed. The results of this boundary-element-method (BEM) template matching algorithm applied to cell contour tracking are shown in Figure 3, where the traction distribution applied to the template is shown on the right.
By visually extracting geometry changes on a biomembrane, the geometry changes were used to estimate applied forces using the biomembrane mechanical models. Forces on a biomembrane can be visually observed and controlled, thus creating a framework for vision and force assimilated cell manipulation.