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. 2023 Oct 23:1279:341830.
doi: 10.1016/j.aca.2023.341830. Epub 2023 Sep 17.

High-resolution integrated microfluidic probe for mass spectrometry imaging of biological tissues

Xiangtang Li  1 , Hang Hu  1 , Julia Laskin  2
Affiliations

High-resolution integrated microfluidic probe for mass spectrometry imaging of biological tissues

Xiangtang Li et al. Anal Chim Acta. .

Abstract

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. In this study, we designed a new probe that enables imaging of biological samples with high spatial resolution. The new probe design features smaller primary and spray channels and an entirely 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. The robustness of the high-resolution iMFP allowed us to perform first imaging experiments with both high spatial resolution and high throughput, which is particularly advantageous for high-resolution imaging of large tissue sections of interest to most MSI applications. Overall, the new probe design opens opportunities for mapping of biomolecules in biological samples with high throughput and cellular resolution, which is important for understanding biological systems.

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Conflict of interest statement

Declaration of competing interest The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
(A) A schematic drawing of the high-resolution iMFP; (B) A schematic illustration of the sampling port and liquid bridge between the probe and sample surface; (C) A photograph of the iMFP in front of a mass spectrometer inlet and the sampling port on top of a glass surface near the tissue sample; (D) A photograph showing the size of the iMFP; (E) and (F) Photographs of the iMFP-based imaging platform in front of a mass spectrometer showing: 1, instrument mounting flange; 2, extended ion transfer tube; 3; the iMFP; 4, XYZ inline micro-positioner; 5, sample holder; 6, motorized XYZ stage; 7, Dino-Lite microscope; 8, high-voltage connector; 9, syringe delivering the working solvent; 10, fused-silica capillary (50 μm i.d) supplying the working solvent to the iMFP.
Figure 2.
Figure 2.
Optical image of a mouse uterine tissue section and representative positive mode ion images of phospholipids acquired using the high-resolution iMFP. PC, LPC, SM, and PE represent phosphatidylcholine, lysophosphatidylcholine, sphingomyelin,and phosphatidylethanolamine, respectively. Scale bar is 1 mm. The intensity scale changes from black (low) to yellow (high). Abbreviation: luminal epithelium (LE), glandular epithelial cells (GE), stroma that surrounds LE and GE (S).
Figure 3.
Figure 3.
Estimation of the spatial resolution using an ion image of the [M+Na]+ ion of SM 34:1 normalized to the TIC (A). Line profile was extracted along the white line. (B) An expanded view of the region between LE and stroma regions. (C) An example of a line profile used to estimate the spatial resolution based on the steepest chemical gradients. Red dashed lines highlight the regions over which the signal changes between 20% and 80% of its maximum span.
Figure 4.
Figure 4.
(A) Single-pixel mass spectra obtained using the high-resolution iMFP at two scan rates of 0.02 and 0.2 mm/s showing comparable sensitivity. (B) Representative positive ion images obtained for mouse uterine tissue sections at scan rates of (i) 0.02 and (ii) 0.2 mm/s. Scale bar is 1 mm; The intensity scale changes from black (low) to yellow (high).
Figure 5.
Figure 5.
An optical image of the cerebellum region of a mouse brain tissue section analyzed in this study and representative positive mode ion images of endogenous molecules in the tissue. Each image corresponds to a sodium adduct [M+Na]+ of a unique phospholipid. Blue arrows highlight the molecular layer (M), Purkinje layer (P), granular layer (G), and white matter (W). Scale bar is 1 mm; The intensity scale changes from black (low) to yellow (high).
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