A high-throughput label-free time-stretch acoustofluidic imaging cytometer for single-cell mechanotyping
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RESEARCH PAPER
A high‑throughput label‑free time‑stretch acoustofluidic imaging cytometer for single‑cell mechanotyping Wanyue Zhao1 · Han Wang2 · Yingxue Guo1 · Kai Sun2 · Zhen Cheng3 · Hongwei Chen1 Received: 23 February 2020 / Accepted: 6 October 2020 / Published online: 17 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Current circulating tumor cells (CTC) detection methods have to compromise between sensitivity and throughput. Highthroughput 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 labelfree 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. Keywords Optical time stretch · Acoustofluidics · Optofluidics · Imaging cytometry · Cell mechanotyping
1 Introduction High sensitivity and fidelity detection of circulating tumor cells (CTC) is regarded a promising approach for the study of cancer disease, as non-invasive biopsy can be used as cancer diagnosis and prognosis biomarkers. Current gold standard of CTC liquid biopsy is immunoaffinity-based methods such as immunomagnetic affinity-based CTC capturing (Hoshino et al. 2011). But these methods suffer from low sensitivity * Han Wang [email protected] * Hongwei Chen [email protected] 1
Department of Electronic Engineering, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing 100084, People’s Republic of China
2
Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, People’s Republic of China
3
Department of Automation, Tsinghua University, Beijing 100084, People’s Republic of China
due to insufficient binding and variance of cell surface biomarkers (Ghazani et al. 2013). Serial time-encoded amplified microscopy (STEAM) (Goda et al. 2009) is a continuous ultrafast imaging technology enabled by optical time-stretch (Goda and Jalali 2013) which achieves unprecedented imaging speed of millions of frames per second. It images, counts and phenot
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