Abstract
Single cell manipulation technology has been widely applied in biological fields, such as cell injection/enucleation, cell physiological measurement, and cell imaging. Recently, a biochip platform with a novel configuration of electrodes for cell 3D rotation has been successfully developed by generating rotating electric fields. However, the rotation platform still has two major shortcomings that need to be improved. The primary problem is that there is no on-chip module to facilitate the placement of a single cell into the rotation chamber, which causes very low efficiency in experiment to manually pipette single 10-micron-scale cells into rotation position. Secondly, the cell in the chamber may suffer from unstable rotation, which includes gravity-induced sinking down to the chamber bottom or electric-force-induced on-plane movement. To solve the two problems, in this paper we propose a new microfluidic chip with manipulation capabilities of single cell trap and single cell 3D stable rotation, both on one chip. The new microfluidic chip consists of two parts. The top capture part is based on the least flow resistance principle and is used to capture a single cell and to transport it to the rotation chamber. The bottom rotation part is based on dielectrophoresis (DEP) and is used to 3D rotate the single cell in the rotation chamber with enhanced stability. The two parts are aligned and bonded together to form closed channels for microfluidic handling. Using COMSOL simulation and preliminary experiments, we have verified, in principle, the concept of on-chip single cell traps and 3D stable rotation, and identified key parameters for chip structures, microfluidic handling, and electrode configurations. The work has laid a solid foundation for on-going chip fabrication and experiment validation.
Highlights
Biological cells need to be manipulated in many scenarios, such as cell characterization, sorting, injection, and enucleation [1,2,3,4,5]
Mechanical means involve direct contact between the manipulator probes and cell surface, which poses the risk of damaging the cell structure, as the cell is quite delicate and sticky [9,10]
Magnetic means could manipulate cells on the premise that cells should be embedded with magnetic nano-particles before moving or rotating under a magnetic field
Summary
Biological cells need to be manipulated in many scenarios, such as cell characterization, sorting, injection, and enucleation [1,2,3,4,5]. When used for cell rotation, DEP technology has long been configured in such a way that several (normally four) planar electrodes are formed, like house walls, enclosing a virtual electric-field-filled chamber or cage, inside which the cell rotates. In our previous study [24], we developed a new DEP configuration that enabled 3D cell rotation on a chip that is composed of four side-walls electrodes and two bottom electrodes. The developed chip platform has the advantages of top-open and transparent structure, facilitating cell sample loading, external access to the cell sample after rotation, and non-stop observation of the cell sample during rotation It still suffers from the following two major problems: (1) Like many other similar studies, we used a micropipette to place a single cell in the electrode chamber. The design and simulation results provide insightful angles to solve the existing problems and to pave the way for the phase of our chip fabrication and experimental validation
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