Wenhao Huang

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

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.

Mechanical Modeling of Biological Cells in Microinjection

Microinjection is an effective technique to introduce foreign materials into a biological cell. Although some semi-automatic and fully-automatic microinjection systems have been developed, a full understanding of the mechanical response of biological cells to injection operation remains deficient. In this paper, a new mechanical model based on membrane theory is proposed. This model establishes a relationship between the injection force and the deformation of biological cells with the quasi-static equilibrium equations, which are solved by the Runge-Kutta numerical method. Based on this model, other mechanical responses can also be inferred, such as the effect of the injector radius, the membrane stress and tension distribution, internal cell pressure, and the deformed cell shape. To verify the proposed model, experiments are performed on microinjection of zebrafish embryos at different developmental stages and medaka embryos at the blastula stage. It is demonstrated that the modeling results agree well with the experimental data, which shows that the proposed model can be used to estimate the mechanical properties of cell biomembranes. (In this paper, biomembrane refers to the membrane-like structures enveloping cells.)

Mechanical force characterization in manipulating live cells with optical tweezers

Laser trapping with optical tweezers is a noninvasive manipulation technique and has received increasing attentions in biological applications. Understanding forces exerted on live cells is essential to cell biomechanical characterizations. Traditional numerical or experimental force measurement assumes live cells as ideal objects, ignoring their complicated inner structures and rough membranes. In this paper, we propose a new experimental method to calibrate the trapping and drag forces acted on live cells. Binding a micro polystyrene sphere to a live cell and moving the mixture with optical tweezers, we can obtain the drag force on the cell by subtracting the drag force on the sphere from the total drag force on the mixture, under the condition of extremely low Reynolds number. The trapping force on the cell is then obtained from the drag force when the cell is in force equilibrium state. Experiments on numerous live cells demonstrate the effectiveness of the proposed force calibration approach.

Mechanical modeling of red blood cells during optical stretching.

Mechanical properties of red blood cells (RBCs) play an important role in regulating cellular functions. Many recent researches suggest that the cell properties or deformability may be used as a diagnostic indicator for the onset and progression of some human diseases. Although optical stretcher (OS) has emerged as an effective tool to investigate the cell mechanics of RBCs, little is known about the deformation behavior of RBCs in an OS. To address this problem, the mechanical model proposed in our previous work is extended in this paper to describe the mechanical responses of RBCs in the OS. With this model, the mechanical responses, such as the tension distribution, the effect of cell radius, and the deformed cell shapes, can be predicted. It is shown that the results obtained from our mechanical model are in good agreement with the experimental data, which demonstrates the validity of the developed model. Based on the derived model, the mechanical properties of RBCs can be further obtained. In conclusion, this study indicates that the developed mechanical model can be used to predict the deformation responses of RBCs during optical stretching and has potential biomedical applications such as characterizing cell properties and distinguishing abnormal cells from normal ones.

Characterizing Mechanical Properties of Biological Cells by Microinjection

Microinjection has been demonstrated to be an effective technique to introduce foreign materials into biological cells. Despite the advance, whether cell injection can be used to characterize the mechanical properties of cells remains elusive. In this paper, extending the previously developed mechanical model, various constitutive materials are adopted to present the membrane characteristics of cells. To demonstrate the modeling approach and identify the most appropriate constitutive material for a specific biomembrane, finite element analysis (FEA) and experimental tests are carried out. It is shown that the modeling results agree well with those from both FEA and experiments, which demonstrates the validity of the developed approach. Moreover, Yeoh and Cheng materials are found to be the best constitutive materials in representing the deformation behaviors of zebrafish embryos and mouse embryos (or oocytes), respectively. Also, the mechanical properties of zebrafish embryos at different developmental stages and mouse embryos (or oocytes) are characterized.

Force analysis and path planning of the trapped cell in robotic manipulation with optical tweezers

Laser trapping in the near infrared regime is a noninvasive and convenient manipulation tool, which can be utilized as micromanipulator for a large number of biological applications. Increasing demands for both accuracy and efficiency in cell manipulation highlight the need for automation process that integrates robotics and tweezers technologies. In this paper, we propose a robotic manipulation system with optical tweezers, and analyze the force applied on the trapped cell for design of an optimal trapping strategy. The dynamic motion of the cell with consideration of both the trapping and the viscous forces is analyzed, based on which the motion profile of the motorized stage is designed to ensure both safety and efficiency of the cell delivery. A modified A-star algorithm is used for path planning in transporting cells. Experiments are performed on manipulating the yeast cells to demonstrate the effectiveness of the proposed approach.

Force and motion analysis for automated cell transportation with optical tweezers

Optical tweezers utilize highly focused laser beam to produce optical forces on the object, and can be used for trapping, orienting and moving micro-/nano-scaled particles, ideally for biological cells. At present time, the majority of tasks with optical tweezers are carried out manually. Increasing demands for both accuracy and efficiency in cell manipulation highlight the need for automation process that integrates robotics and optical tweezer technologies. In this paper, we propose to use a robot-tweezer manipulation system to automatically transport cells. We calibrate the forces applied to the trapped cell by a dynamic viscous-drag-force method to determine the optimal motion parameters, and adopt a modified A-star algorithm for path planning during automated transportation. Experiments are performed on manipulating living cells to demonstrate the effectiveness of the proposed approach.

Mechanical modeling characterization of biological cells using microrobotics cell injection test bed

Mechanical properties of biological cells play an important role in regulating cellular functions. Some micromanipulation methods have been reported in the literature to measure cell mechanics, but they are either high-costly or difficultly-operated. This paper presents our approach to use microrobotic cell injection technology as the test bed to characterize the mechanical properties of biological cells, by virtue of low cost and easy operation. By extending our previous work [41], we develop a mechanical model to interpret the mechanical responses during microinjection and extract the cells properties. Both finite element analysis and microinjection experiments are performed to verify the mechanical model. It is shown that the results obtained from the proposed mechanical model agree well with that obtained from finite element analysis and the experiments. Elastic moduli of zebrafish embryos at different developmental stages are characterized. This demonstrates not only the validity of the proposed model but also the fact that the microrobotic cell injection technology combining with the mechanical model can be used to characterize the mechanical properties of biological cells.

A mechanical model of biological cells in microinjection

Microinjection is an effective technique to introduce foreign materials into a biological cell. Although great developments have been achieved, a full understanding of the mechanical response of biological cells to injection operation remains deficient. In this paper, a mechanical model based on membrane theory is proposed. This model utilizes the Mooney-Rivlin material to model the deformation of biomembrane. The relationship between the injection force and the deformation of biological cells is established through the quasi-static equilibrium equations, which are solved by the Runge-Kutta numerical method. To verify the mechanical model, experiments are performed on microinjection of zebrafish and medaka embryos. It is demonstrated that the modeling results agree well with the experimental data, which shows that the proposed model can be used to estimate the mechanical properties of cell biomembranes.

Robotic manipulation of human red blood cells with optical tweezers for cell property characterization

Cell manipulation has received considerable attentions in recent years. Most of cell manipulations are performed manually without guarantee of high precision and high throughput. This paper reports our latest research on integrating robotics technologies into optical tweezers system for manipulation and biomechanical characterization of human red blood cells (RBCs). We first demonstrate the effectiveness of the robot-tweezers system in manipulation of micro-beads, which is followed by stretching RBCs to different levels of deformations. The whole manipulation process is conducted with visual guidance and position feedback control, where the cell stretching direction is determined automatically through image analysis. The relationship between the stretching force and the induced deformation is obtained through force calibration and image processing. To characterize the mechanical properties of RBCs from the obtained experimental results, a mechanical model based cell property characterization strategy is introduced. Comparing the modeling results to the experimental data, the mechanical properties of human RBCs are characterized. In conclusion, this study demonstrates that the robotic manipulation technology with optical tweezers can be used to manipulate biological cells, and further, to characterize the biomechanical properties based on the cell mechanical model.