High-Resolution Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Tissues

Nanospray desorption electrospray ionization (nano-DESI) is an ambient ionization technique that enables molecular imaging of biological samples with high spatial resolution. We have recently developed an integrated microfluidic probe (iMFP) for nano-DESI mass spectrometry imaging (MSI) that significantly enhances the robustness of the technique. Herein, we report the design and performance of a second-generation iMFP for imaging with high spatial resolution. The new iMFP features smaller primary and spray channels and a new configuration of the sampling port that enables robust imaging of tissues with a spatial resolution of 8-10 µm. We demonstrate the spatial resolution, sensitivity, durability, and throughput of the iMFP by imaging mouse uterine and brain tissue sections. With a scan rate of 0.2 mm/s, we obtained high-resolution images of a mouse uterine tissue section (scanned area: 2.9 mm × 3.2 mm) in less than 29 minutes without sacrificing sensitivity. This corresponds to a 10-fold improvement in the experimental throughput in comparison with previously reported high-resolution nano-DESI MSI experiments. Overall, the new probe design opens opportunities for mapping biomolecules in biological samples with high throughput and cellular resolution, which is important for understanding biological systems.