On-chip refractive index cytometry for whole-cell deformability discrimination

Abstract

On-chip high-throughput phenotyping of single cells has gained a lot of interest recently due to the discrimination capability of label-free biomarkers such as whole-cell deformability and refractive index. Here we present on-chip refractive index cytometry (RIC) for whole-cell deformability at a high measurement rate. We have further exploited a previously published on-chip optical characterization method which enhances cellular discrimination through the refractive index measurement of single cells. The proposed on-chip RIC can simultaneously probe the cellular refractive index, effective volume and whole-cell deformability while reaching a measurement rate up to 5000 cells per second. Additionally, the relative position of the nucleus inside the cell is reflected by the asymmetry of the measured curve. This particular finding is confirmed by our numerical simulation model and emphasized by a modified cytoskeleton HL-60 cells model. Furthermore, the proposed device discriminated HL-60 derived myeloid cells such as neutrophils, basophils and promyelocytes, which are indistinguishable using flow cytometry. To our knowledge, this is the first integrated device to simultaneously characterize the cellular refractive index and whole-cell deformability, yielding enhanced discrimination of large myeloid cell populations.