Efficient Sample Preparation System for Multi-Omics Analysis via Single Cell Mass Spectrometry

Area of Science:

• Biochemistry
• Analytical Chemistry
• Cell Biology

Background:

• Mass spectrometry (MS) is crucial for metabolome, lipidome, and proteome analysis.
• Single-cell multi-omics analysis faces challenges in cell manipulation and in-situ digestion/extraction.
• Existing methods lack efficiency and automation for comprehensive single-cell omics.

Purpose of the Study:

• To develop a streamlined, automated strategy for highly efficient single-cell multi-omics analysis using MS.
• To overcome limitations in single-cell manipulation and in-situ analysis.
• To enable deeper investigation of cellular heterogeneity and phenotyping.

Main Methods:

• A 10-pL microwell chip for housing and digesting single cells in 5 minutes.
• An automated picoliter extraction system for sequential sampling of metabolites, phospholipids, and proteins.
• Rapid MS/MS acquisition for sensitive detection.

Main Results:

• Demonstrated ultra-fast (5 min) protein digestion, 144x faster than bulk methods.
• Achieved simultaneous extraction and MS analysis of metabolites, phospholipids, and proteins from single cells.
• Detected 1391 analytes from a single cell within 10 minutes.
• Showcased a 40% increase in cancer cell classification accuracy using multi-omics compared to single-omics.

Conclusions:

• The developed automated single-cell MS strategy offers high efficiency for multi-omics analysis.
• This approach facilitates the investigation of cell heterogeneity and phenotyping.
• The method holds significant potential for biomedical applications requiring detailed cellular insights.