Researchers have been using flow cytometry since the 1950s to study immune cells and other cell types. Traditional flow cytometry has limitations in detecting multiple proteins due to the number of fluorophores that can be distinguished. In 2009, mass cytometry was introduced, allowing the quantification of 50 proteins in single cells. However, sensitivity was reduced compared to traditional methods. A recent collaboration led by the Wyss Institute at Harvard University has developed a method to enhance the sensitivity of mass cytometry and image mass cytometry using DNA nanotechnology.
The new method, called Amplification by Cyclic Extension (ACE), amplifies protein signals produced by antibody-bound metal isotopes, allowing the simultaneous detection of more than 30 different proteins with high sensitivity. This advancement enables the quantification of rare proteins and the study of complex biological tissue changes. ACE has the potential to provide a deeper understanding of normal and pathological biological processes by facilitating single-cell analysis with high sensitivity, multiplexing, and throughput.
The research team was able to use ACE to study epithelial-mesenchymal transitions in breast cancer cells, analyze the activation of a complex network of intracellular signaling proteins in T cells, and investigate injury-induced T-cell paralysis. They also demonstrated the utility of ACE for spatial analysis of proteins in tissue sections using image mass cytometry in a study of polycystic kidney disease.
Overall, ACE represents a significant advancement in cytometric analysis, allowing for the detection of a broad range of low-abundance proteins that were challenging to quantify using previous methods. The technology has the potential to revolutionize the study of single cells and tissues, providing new insights into biological processes and diseases. The findings of this research were published in Nature Biotechnology.
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