Electrical Detection and Actuation of Single Biological Cells with Application to Deformability Cytometry for Markerless Diagnostics.

摘要

An all-electrical system is developed to actuate and detect single biological cells in a microfluidic channel for diagnostic applications. Interdigitated electrodes fabricated on the channel floor transfer a high frequency signal for capacitance detection and a low frequency signal for dielectrophoretic actuation. In the fluid-filled channel, a pressure-driven flow propels single biological cells, which induce time-dependent capacitance signatures as they pass over the electrodes. With a sub-attofarad (≈ 0.15 aF RMS, 53 Hz bandwidth) capacitance resolution, this system detects biological cells (e.g., 1 yeast cell ≈ 50 aF) and their deflections (1 µm ≈ 5 aF) from exerted dielectrophoretic forces (≥ 5 pN). Electrical detection of cell actuation by strong DEP forces provides an avenue for both inducing and monitoring the deformation of viscoelastic cells.;A strong and repulsive dielectrophoretic force can be used to press a biological cell into a channel wall. When this occurs, the mechanical properties of the cell can be investigated by capacitively monitoring the cell-to-wall interaction. The nature of the resulting interaction is shown to depend on the mechanical properties of the cell (surface morphology and viscoelastic properties). Various mammalian cell types such as Chinese Hamster Ovary (CHO) cells, mouse fibroblasts, human blood cells, human breast cells and their tumorogenic phenotypes are investigated using this system. Between these populations, the effective Young's modulus varies widely from 20 Pa (neutrophils) to 1-2 GPa (polystyrene microspheres). The viability and phenotype of a biological cell are known to reflect its mechanical and electrical properties. Consequently, this work investigates whether dielectrophoretically induced cell deformations are correlated with corresponding variations in capacitance, which could be used for discriminating cell phenotypes in the future.