Deterministic microfluidic ratchet based on the deformation of individual cells

We present a microfluidic ratchet that exploits the deformation of individual cells through microscale funnel constrictions. The threshold pressure required to transport single cells through such constrictions is greater against the direction of taper than along the direction of taper. This physical asymmetry combined with an oscillatory excitation can enable selective and irreversible transport of individual cells in low Reynolds number flow. We devised a microfluidic device to measure the pressure asymmetry across various geometries of funnel constrictions. Using a chain of funnel constrictions, we showed that oscillatory pressure enables ratcheting transport when the pressure amplitude and oscillation period exceeds the threshold required to transport single cells. These experiments demonstrate the potential of using this mechanism to selectively transport biological cells based on their internal mechanics, and the potential to separate cells based on cell morphology or disease state.

Figure 1

Deformation of a single cell through microscale funnel constrictions in forward and reverse directions. Key parameters of the microstructure include the funnel pore size ($W_0$) and half-angle of the funnel taper (θ).

Figure 2

Design of a two-layer microfluidic device for measuring the pressure required to deform single cells through microscale funnel constrictions. An upper flow layer comprises two sets of 10 funnels arranged in opposite polarity and decreasing in pore size toward the center of the chain. Single cells are introduced at (e) and (f), and then deformed through the funnel chain using the pressure difference between (c) and (d), which is attenuated 100 times from the external pressure applied across (a) and (b). The pressure application and cell inlet processes are activated using the control layer valves V1–V4.

Figure 3

(a) Forward and reverse threshold pressures required to deform a single MLC (${\Phi }_{\mathrm{cell}}$ $=$ 15.6 μm) through a 10° funnel constriction. The model curves have been fitted using a cortical tension of 750 pN/μm. (b) Pressure asymmetry for 10°, 5°, and 0° funnel constrictions as a function of ${\Phi }_{\mathrm{cell}}$/$W_0$. Data points shown are the average pressures from 3–4 measurements on the same cell, while the error bar shows the range of the measured results.

Figure 4

(a) The displacement of a single MLC (${\Phi }_{\mathrm{cell}}$ $=$ 10.5 μm) in the funnel chain ($W_0$ $=$ 6 μm) with a 0.5 Hz oscillation at various pressure amplitudes. An offset has been added to the initial positions of these curves such that they begin at the same point. The no-funnel curve is a control experiment that tracks the cell motion in an unconstrained microchannel prior to entering the funnel chain. (b) Frequency dependence of ratchet motion with an oscillation pressure amplitude of 150 Pa.