The positioning of biological cells has become increasingly important in biomedical research such as drug discovery, cell-to-cell interaction, and tissue engineering. Significant demand for both accuracy and productivity in cell manipulation highlights the need for automated cell transportation with integrated robotics and micro/nano-manipulation technologies. Optical tweezers, which use highly focused low-power laser beams to trap and manipulate particles at the micro/nanoscale, can be treated as special robot ‘end-effectors’ to manipulate biological objects in a noninvasive way. In this paper, we propose to use a robot-tweezer manipulation system for automatic transportation of biological cells. A dynamics equation of the cell in an optical trap is analyzed. Closed-loop controllers are designed for positioning single cells as well as multiple cells. A synchronization control technology is utilized for multicell transportation with maintained cell pattern. Experiments are performed on transporting live cells to demonstrate the effectiveness of the proposed approach.
Optical tweezers are widely used for noninvasive and precise micromanipulation of living cells to understand biological processes. By focusing laser beams on cells, direct cell manipulation with optical tweezers can achieve high precision and flexibility. However, direct exposure to the laser beam can lead to negative effects on the cells. These phenomena are also known as photobleaching and photodamage. In this study, we proposed a new indirect cell micromanipulation approach combined with a robot-aided holographic optical tweezer system and 3D nano-printed microtool. The microtool was designed with a V-shaped head and an optical handle part. The V-shaped head can push and trap different sizes of cells as the microtool moves forward by optical trapping of the handle part. In this way, cell exposure to the laser beam can be effectively reduced. The microtool was fabricated with a laser direct writing system by two-photon photopolymerization. A control strategy combined with an imaging processing algorithm was introduced for automated manipulation of the microtool and cells. Experiments were performed to verify the effectiveness of our approach. First, automated microtool transportation and rotation were demonstrated with high precision. Second, indirect optical transportations of cells, with and without an obstacle, were performed to demonstrate the effectiveness of the proposed approach. Third, experiments of fluorescent cell manipulation were performed to confirm that, indicated by the photobleaching effect, indirect manipulation with the microtool could induce less laser exposure compared with direct optical manipulation. The proposed method could be useful in complex biomedical applications where precise cell manipulation and less laser exposure are required.
This paper presents an approach to manipulating cell adhesions using optical tweezers for cell-to-cell interactions at single cell level. A case study of investigating the adhesions between leukemia cells and bone marrow stromal cells is reported. First, the trapping force imposed on the cell is calibrated and the viability of leukemia cells after optical trapping is tested and verified. This is for demonstrating the feasibility of the proposed optical manipulation method. Second, properties of adhesions of leukemia cells K562 on stromal cells M210B4 from mouse and HS5 from human are characterized. Based on characterization results, we classify adhesions into three categories namely tightly adherent, loosely adherent or free suspending. Finally, the adhesion abilities of K562 on M210B4 and HS5 are changed by adding heparin into culture medium, which demonstrates the specificity of the adhesion. The important contribution of this paper lies in development of a dexterous cell manipulation method to characterize cell adhesion properties, which helps create a new opportunity to investigate cell-to-cell interactions at single cell level.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.