We demonstrate a highly-sensitive and label-free method for characterizing cells based on cell-surface receptors. The method involves measuring a current pulse generated when an individual cell passes through an artificial pore. When the pore is functionalized with proteins, specific interactions between a cell-surface marker and the functionalized proteins retard the cell, thus leading to an increased pulse duration that indicates the presence of that specific biomarker. For proof-of-principle, we successfully screened murine erythroleukemia cells based on their CD34 surface marker in both a single and mixed population of cells. Further, we developed a unified constrained statistical model for estimating the ratios of cells in a mixed population. Finally, we demonstrated our ability to screen a small number of cells (hundreds or less) with high accuracy and sensitivity. Overall, our pore-based method is broadly applicable and, in the future, could provide a full range of in vitrocell-based assays.
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