Spray-Capillary-Based Capillary Electrophoresis Mass Spectrometry for Metabolite Analysis in Single Cells

Single-cell capillary electrophoresis
mass spectrometry (CE-MS)
is a promising platform to analyze cellular contents and probe cell
heterogeneity. However, current single-cell CE-MS methods often rely
on offline microsampling processes and may demonstrate low sampling
precision and accuracy. We have recently developed an electrospray-assisted
device, spray-capillary, for low-volume sample extraction.
With the spray-capillary, low-volume samples (pL–nL) are drawn
into the sampling end of the device, which can be used directly for
CE separation and online MS detection. Here, we redesigned the spray-capillary
by utilizing a capillary with a <15 μm tapered tip so that
it can be directly inserted into single cells for sample collection
and on-capillary CE-MS analysis. We evaluated the performance of the
modified spray-capillary by performing single-cell microsampling on
single onion cells with varying sample injection times and direct
MS analysis or online CE-MS analysis. We have demonstrated, for the
first time, online sample collection and CE-MS for the analysis of
single cells. This application of the modified spray-capillary device
facilitates the characterization and relative quantification of hundreds
of metabolites in single cells.