Digital Raman assay for single-molecule protein sequencing in single live cells (LiveProSeq)

Current single-cell proteomics analysis methods based on mass spectroscopy cannot obtain continuous time-resolved data because they have to lyse or kill the cells. They cannot analyze proteins extracted from single live cell, because the extracted proteins cannot be amplified nor the mass spectrometer is sensitive enough .
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Project information

Project duration

-

Project funder

Biocenter Oulu

Project coordinator

University of Oulu

Unit and faculty

Research Unit of Health Sciences and Technology
Faculty of Medicine

Contact information

Project leader

Other persons

Researchers

Project description

While single-cell DNA/RNA sequencers have revolutionized genomics and transcriptomics, no corresponding technologies exist for single-cell proteomics. This BCO project aims to develop a single-molecule protein analysis technology to identify and quantify peptides and proteins from single live cell by combining the PI's plasmonic nanopore sensor, the nanotube platform with the co-I's deep learning analysis. Being synergetic with the PI's Academy Research Fellow project (TwoPoreProSeq) and BCO emerging project (DigiRaman), the BCO project will integrate experts from the University of Oulu in the field of nanobiotechnology, nanophotonic biosensors, cellular biology and artificial intelligence. When fully implemented, the proposed technology will open a new era for single-live-cell proteomics able to profile continuously proteins and protein modifications with single-molecule sensitivity in single live cell, benefiting early diagnosis of diseases, drug development, and precision medicine.

Research groups

The Jianan Lab of Nanophotonic Biosensors

Key publications

Zhao, Yingqi, Kuo Zhan, Pei-Lin Xin, Zuyan Chen, Shuai Li, Francesco De Angelis, and Jian-An Huang. "Single-Molecule SERS Discrimination of Proline from Hydroxyproline Assisted by a Deep Learning Model." Nano Letters 25, no. 18 (2025): 7499-7506.

Huang, Jian‐An, Mansoureh Z. Mousavi, Giorgia Giovannini, Yingqi Zhao, Aliaksandr Hubarevich, Miguel A. Soler, Walter Rocchia, Denis Garoli, and Francesco De Angelis. "Multiplexed discrimination of single amino acid residues in polypeptides in a single SERS hot spot." Angewandte Chemie International Edition 59, no. 28 (2020): 11423-11431.

Huang, Jian-An, Valeria Caprettini, Yingqi Zhao, Giovanni Melle, Nicolò Maccaferri, Lieselot Deleye, Xavier Zambrana-Puyalto et al. "On-demand intracellular delivery of single particles in single cells by 3D hollow nanoelectrodes." Nano letters 19, no. 2 (2019): 722-731.

Caprettini, Valeria, Jian‐An Huang, Fabio Moia, Andrea Jacassi, Carlo Andrea Gonano, Nicolò Maccaferri, Rosario Capozza, Michele Dipalo, and Francesco De Angelis. "Enhanced Raman investigation of cell membrane and intracellular compounds by 3D plasmonic nanoelectrode arrays." Advanced Science 5, no. 12 (2018): 1800560.