A high-throughput label-free time-stretch acoustofluidic imaging cytometer for single-cell mechanotyping

Abstract

Current circulating tumor cells (CTC) detection methods have to compromise between sensitivity and throughput. High-throughput imaging cytometer based on serial time-encoded amplified microscopy (STEAM) facilitates CTC detection at single-cell sensitivity from abundant cells. However, this method lacks the information to spot heterogeneity of cells with high morphological similarity. Researches on cell biophysical properties suggest cell mechanotyping can be an indicator of phenotypic heterogeneity to improve classification ability of STEAM cytometer. Here, we present a high-throughput label-free acoustofluidic imaging cytometer for single-cell mechanotyping based on STEAM and acoustofluidic technology. The generated acoustic resonance field translocates cells to different transversal exit positions under continuous flow according to their intrinsic biophysical properties. Such displacements are recorded with images simultaneously using STEAM cytometry at approximately 2000 cells/s. We experimentally verified that our method accounting for both cell images and acoustic displacements can improve mechanotyping accuracy by 12% upon image-based phenotyping method. This new acoustofluidic imaging cytometer facilitates high-accuracy and high-throughput imaging cytometry for single-cell CTC mechanotyping.