Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

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.

Review: Microbial analysis in dielectrophoretic microfluidic systems

“…However, a number of methodologies have recently emerged 199 , including those using conducting polymers 200 , silver-PDMS 201 , liquid metals 202 , screen printing 203 and vapor deposition, constructed by techniques of micromolding 204 , semiconductor fabrication 205,206,207,208,209 , and low-cost bonding methods on hybrid platforms 210,203 . The reduced dead volumes of such 3D electrode platforms have been applied to enhance the spatial extents of the field non-uniformity 211,212 to enable high throughput separations 213,214 , cytometry 215,216 , sample enrichment for biomolecular determination 217,218 , sample transport by traveling-wave dielectrophoresis 219,220,221 , and dielectric characterization of cells by electro-rotation 222,223,224 .…”

Sequential Cell-Processing System by Integrating Hydrodynamic Purification and Dielectrophoretic Trapping for Analyses of Suspended Cancer Cells

“…The other is the negative DEP whereby cells are repelled away from the strong electric field when the value of RE(K(2π f )) is less than 0. These two different movements were used to manipulate particles, including cells and microbeads [30][31][32][33][34].…”

Microfluidics cell sample preparation for analysis: Advances in efficient cell enrichment and precise single cell capture

“…Because most biological cells have dielectric characteristics in an external electric field, cells in suspension can be controlled by DEP force or torque. [70][71][72] Cells can be stimulated to travel to the region with a strong electric field by a positive DEP force in the non-uniform electric field, or conversely, to the area with a weak electric field by a negative DEP force.…”

“…14(c)). 72 Based on the least flow resistance principle, one single cell can be captured at trap site and translated into the electrode chamber for 3D rotation. Furthermore, using unique signal configuration can facilitate in-plane cell centering in the rotation chamber and prevent the rotating cell from sinking down to the bottom.…”