Out-of-plane Rotation Control of Biological Cells with a Robot-Tweezers Manipulation System for Orientation-based Cell Surgery

Mingyang Xie; Adnan Shakoor; Yajing Shen; James K. Mills; Dong Sun

In many cell surgery applications, cell must be oriented properly such that the micro-surgery tool can access the target components with minimum damage to the cell. In this paper, a scheme for out of image plane orientation control of suspended biological cells using robotic controlled optical tweezers is presented for orientation-based cell surgery. Based on our previous work on planar cell rotation using optical tweezers, the dynamic model of cell out-of-plane orientation control is formulated by using the T-matrix approach. Vision-based algorithms are developed to extract the cell out of image plane orientation angles, based on 2D image slices obtained under optical microscope. A robust feedback controller is then proposed to achieve cell out-of-plane rotation. Experiments of automated out of image plane rotational control for cell nucleus extraction surgery are performed to demonstrate the effectiveness of the proposed approach. This approach advances robot-aided single cell manipulation and produces impactful benefits to cell surgery applications such as nucleus transplantation and organelle biopsy in precision medicine.

DOI

Applying Combined Optical Tweezers and Fluorescence Microscopy Technologies to Manipulate Cell Adhesions for Cell-to-Cell Interaction Study

Gou, X., Han, H.; Leung, A.Y.H.; Sun, D.
Cell-to-cell interactions are important for the regulation of various cell activities, such as proliferation, differentiation, and apoptosis. This paper presents an approach to studying cell-to-cell interactions at a single cell level through manipulating cell adhesions with optical tweezers. Experiments are performed on leukemia cancer cells and stromal cells to demonstrate the feasibility of this method. After the adhesion properties of leukemia cells on stromal cells are characterized, fluorescence intensity is used as a label to study the Wnt signaling pathway of leukemia cells. The activities of the Wnt signaling pathway of K562 cells on M210B4 and HS5 cells are examined based on fluorescence analysis. The reliability of the fluorescence imaging is confirmed through comparison to traditional flow cytometry analysis. The proposed approach will offer new avenues to investigate otherwise inaccessible mechanisms in cell-to-cell interactions.

DOI

Flocking Multiple Microparticles with Automatically Controlled Optical Tweezers: Solutions and Experiments

Chen, H.
This paper presents an efficient approach to achieve microparticles flocking with robotics and optical tweezers technologies. All particles trapped by optical tweezers can be automatically moved toward a predefined regionwithout collision. Themain contribution of this paper lies in the proposal of several solutions to the flocking manipulation ofmicroparticles inmicroenvironments. First, a simple flocking controller is proposed to generate the desired positions and velocities for particles movement. Second, a velocity saturation method is implemented to prevent the desired velocities from exceeding a safe limit. Third, a two-layer control architecture is proposed for the motion control of optical tweezers. This architecture can help make many robotic manipulations achievable under microenvironments. The proposed approachwith these solutions can be applied to many bioapplications especially in cell engineering and biomedicine. Experiments on yeast cells with a robot-tweezers system are finally performed to verify the effectiveness of the proposed approach.
DOI

Mechanical Characterization of Human Red Blood Cells Under Different Osmotic Conditions by Robotic Manipulation With Optical Tweezers

Tan, Y.; Sun, D.; Wang, J.; Huang, W.

The physiological functions of human red blood cells (RBCs) play a crucial role to human health and are greatly influenced by their mechanical properties. Any alteration of the cell mechanics may cause human diseases. The osmotic condition is an important factor to the physiological environment, but its effect on RBCs has been little studied. To investigate this effect, robotic manipulation technology with optical tweezers is utilized in this paper to characterize the mechanical properties of RBCs in different osmotic conditions. The effectiveness of this technology is demonstrated first in the manipulation of microbeads. Then the optical tweezers are used to stretch RBCs to acquire the force–deformation relationships. To extract cell properties from the experimental data, a mechanical model is developed for RBCs in hypotonic conditions by extending our previous work , and the finite element model is utilized for RBCs in isotonic and hypertonic conditions. Through comparing the modeling results to the experimental data, the shear moduli of RBCs in different osmotic solutions are characterized, which shows that the cell stiffness increases with elevated osmolality. Furthermore, the property variation and potential biomedical significance of this study are discussed. In conclusion, this study indicates that the osmotic stress has a significant effect on the cell properties of human RBCs, which may provide insight into the pathology analysis and therapy of some human diseases.

DOI

Moving live dissociated neurons with an optical tweezer

Pine J, Chow G.

The use of an optical tweezer for moving dissociated neurons was studied. The main features of the tweezers are outlined as well as the general principles of its operation. Infrared beams at 980 and 1064 nm were used, focused so as to make a trap for holding neurons and moving them. Absorption by cells at those wavelengths is very small. Experiments were done to evaluate nonsticky substrate coatings, from which neurons could be easily lifted with the tweezers. The maximum speed of cell movement as a function of laser power was determined. Detailed studies of the damage to cells as a function of beam intensity and time of exposure were made. The 980 nm beam was much less destructive, for reasons that are not understood, and could be used to safely move cells through distances of millimeters in times of seconds. An illustrative application of the use of the tweezers to load neurons without damage into plastic cages on a glass substrate was presented. The conclusion is that optical tweezers are an accessible and practical tool for helping to establish neuron cultures of cells placed in specific locations.

DOI