3d illustration of the human brain with visible blood vessels illustrating Alzheimer's disease and dementia, which Biogen is developing treatments for
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A new microchip assay enables researchers to measure hundreds of functional proteins in a single cell. The technology, initially validated in a mouse model of Alzheimer’s disease (AD), could offer new insights into cell function and serve as a tool for molecular diagnostics.

Unlike nucleic acids, proteins cannot be amplified. Therefore, technologies for the analysis of proteins in single cells have not advanced as quickly as those for the analysis of genomes and transcriptomes.

The new technology is called single-cell cyclic multiplex in situ tagging (CycMIST), and its development was led by Jun Wang, PhD, an associate professor from Stony Brook University.

“The CycMIST assay enables comprehensive evaluation of cellular functions and physiological status by examining 100 times more protein types than conventional immunofluorescence staining,” explained Liwei Yang, PhD, the lead author of the Nature Communications article “Cyclic microchip assay for measurement of hundreds of functional proteins in single neurons,” that details the development and validation of CycMIST. “This is a distinctive feature not achievable by any other similar technology.”

Study authors Liwei Yang, PhD (left), and Jun Wang, PhD (right), in the Wang laboratory by the microscope that incorporates the single-cell cyclic multiplex in situ tagging (CycMIST) technology to analyze proteins in single cells. [Jun Wang, PhD]
Using a mouse AD model, the researchers demonstrated the utility of CycMIST. They detected 182 proteins that included surface markers, neuron function proteins, neurodegeneration markers, signaling pathway proteins, and transcription factors. Their analysis revealed the deep heterogeneity of brain cells, distinguished AD markers, and identified AD pathogenesis mechanisms. This functional protein analysis could provide new drug targets for AD, for which there is not yet an effective treatment.

“The CycMIST technology should be broadly applicable to various complex diseases in the future for mechanistic studies at the single-cell functional proteomics level,” wrote the authors.

The authors also believe that CycMIST could also have enormous potential for commercialization, and may advance fields such as molecular diagnostics and drug discovery.

They say that before CycMIST, researchers could only study a few of the protein types in a cell. But this new technology enables researchers to measure and study multiple proteins and their functions. Therefore, they can potentially determine whether a single cell is in a diseased state.

The authors of the study also suggest that the cyclic microchip assay is portable, inexpensive, and could be adapted to any existing fluorescence microscope, which are additional reasons for its marketability if it proves to be effective with subsequent experimentation.

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