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With advantages in biosafety and efficiency, gene delivery based on mechanical approaches has received more and more attention in academic research. In the present paper, a method based on zero-net-mass-flux jet is proposed to apply fluid shear to the moving cells in the microchannel, which causes cell to deform, and then open its mechano-sensitive channel on the cell membrane. This novel method is verified theoretically by numerical simulation in this study. In this paper, an immersed finite element method is utilized to numerically simulate the deformation of red blood cells subjected to zero-net-mass-flux jet during the movement of red blood cells in microchannel, aiming at investigating how to efficiently introduce small molecules into cells. The important parameters of numerical simulation are pressure gradient Δ<i>p</i> along the microchannel, the amplitude <i>A_m</i> and frequency <i>f</i> of the zero-net-mass-flux jet. Through the analysis of the characteristic of flow field and the stress on the red blood cells, we find that when cell surface tension <i>T</i>₀ is greater than critical surface tension <b><i>τ</i></b> _c, the gating of cell surface mechano-sensitive channel will occur, and the percentage of gating <i>P</i>_open on the cell membrane can be obtained at each moment. Addtionally, the channel opening integral <i>I</i> is defined to measure the gating degree of the membrane mechano-sensitive channel under different flow parameters, and the influences of pressure gradient, jet vibration frequency and amplitude on the <i>I</i> are further discussed in order to find the optimized process parameters, The method we proposed is simpler and easier to implement, and the applied fluid shear stress can be controlled precisely, so that it is possible for proteins, genes and other substances to be transported into the cell across the membrane, and to implement reprogramming.

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