Signal amplification by cyclic extension enables high-sensitivity single-cell mass cytometry

Mass cytometry, while enabling simultaneous measurements of numerous proteins in single cells, suffers from sensitivity limitations. This paper introduces Amplification by Cyclic Extension (ACE), a signal amplification technology using thermal-cycling-based DNA in situ concatenation and DNA crosslinking. ACE amplifies signals from over 30 protein epitopes simultaneously, demonstrating utility in low-abundance protein quantification within suspension mass cytometry and imaging mass cytometry (IMC). Applications include characterizing molecular reprogramming during epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions, quantifying signaling network responses in T lymphocytes, and identifying tissue compartments in polycystic kidney tissues.

Xiao-Kang Lun, Kuanwei Sheng, Xueyang Yu, Ching Yeung Lam, Gokul Gowri, Matthew Serrata, Yunhao Zhai, Hanquan Su, Jingyi Luan, Youngeun Kim, Donald E. Ingber, Hartland W. Jackson, Michael B. Yaffe, Peng Yin