Researchers led by the Wyss Institute at Harvard University, along with collaborators from MIT and the University of Toronto, have developed a method to enhance the sensitivity of mass cytometry and image mass cytometry (IMC) using DNA nanotechnology. The new method, called “Amplification by Cyclic Extension” (ACE) significantly increases the sensitivity of mass cytometry, allowing for the simultaneous detection of more than 30 different proteins.
This breakthrough in technology enables researchers to quantitatively detect rare proteins, study complex biological tissue changes, and investigate entire networks of interconnected proteins that regulate immune cell functions. By applying ACE to IMC, researchers were able to identify different cell types and tissue compartments in histological sections and study changes related to the pathology of diseases such as polycystic kidney disease.
The technique involves linking DNA barcodes to antibodies, amplifying signals produced by antibody-bound metal isotopes more than 500-fold. This amplification enables the detection of a broad range of low-abundance proteins that was previously challenging using existing single-cell approaches. ACE provides a platform that achieves high sensitivity, high multiplexing, and high throughput for analyzing single cells in suspension and intact tissues.
The research team used ACE to study epithelial-mesenchymal transitions in breast cancer cells and the signaling responses of T cells. They also investigated injury-induced T-cell paralysis and examined kidney tissue to demonstrate the utility of ACE for spatial analysis of proteins in tissue sections using IMC. The findings were published in Nature Biotechnology and represent a significant advancement in cytometric analysis, providing a deeper understanding of normal and pathological biological processes.
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