Development of a mass spectrometry sampling probe for chemical analysis in surgical and endoscopic procedures

Abstract

A sampling probe based on ambient desorption ionization was designed for in vivo chemical analysis by mass spectrometry in surgical and endoscopic procedures. Sampling ionization of analytes directly from tissue was achieved by sealing the sampling tip against the tissue surface without allowing leakage of the auxiliary gas used for desorption ionization. The desorbed charged species were transferred over a long distance (up to 4 m) through a flexible tube of internal diameter as small as 1/16 in. to the inlet of the mass spectrometer used for analysis. The conditions used for desorption electrospray ionization (DESI) were optimized to achieve biocompatibility for clinical applications while obtaining adequate efficiency for the analysis. This optimization involved the removal of high voltage and use of pure water as a spray solvent instead of the organic solvents or aqueous mixtures normally used. Improved sensitivity was achieved under these conditions by increasing the gas flow rate in the transfer tube. The destructive effect on tissue surfaces associated with typical desorption ionization was avoided by altering the local gas dynamics in the sample area without compromising the overall analysis efficiency.

Figure 1

(a)Schematics of an endoscopic sampling ionization probe which composed of a coaxial capillary sprayer and a transfer tube. A probe with a 4m long, 1/16″ i.d. tubing was used for the analysis of the rat brain tissue section, with the spectra recorded for (b) the white matter and (c) the grey matter. Gas flow rate of 4.3 L/min, high voltage at −4.5kV, methanol/water 1:1 as spray solvent

Figure 2

DESI analysis of 0.5 μg polar lipid extract deposited on the Teflon slides using pure water or methanol as the spray solvent. (a) Analysis with DESI performed close to the MS inlet, gas flow rate of 1.3L/min, solvent flow rate of 3μL/min. (b) Analysis with 4m probe, gas flow rate at 4.3L/min, solvent flow rate at 8μL/min. (c) Signal intensity of plasma-PE (38:6) (m/z=747.52) recorded with probes of different tube lengths from 0.1 to 4.0m.

Figure 3

(a) Intensities and (b) ratio of the intensities of plasma-PE (38:6) (m/z=747.52) recorded as a function of gas flow rate with or without high voltage, desorption ionization performed close to the MS inlet. (c) Intensities and (d) ratio of the intensities of plasma-PE (38:6) (m/z=747.52) recorded as a function of gas flow rate with or without high voltage, a sampling probe of 1 m used for the analysis.

Figure 4

Analysis of rat brain tissue sections using (a) a DESI close to the MS inlet with MeOH/H₂O (1:1) as spray solvent and a high voltage of −4.5kV and (b) a 4m probe with water as spray solvent and no high voltage. (c) Analysis of rat intestine using a 1m probe with water as spray solvent and no high voltage. Gas flow rate, 5.2 L/min for 4 m and 1m probes and 1.5 L/min for DESI.

Figure 5

(a)Noninvasive sampling probe with the gas flow pulled by a diaphragm pump, 1 m long 1/16″ i.d. Tygon tubing, pure water as spray solvent, spray voltage of 0V, gas flow rate from sprayer at 3.8 L/min.(b) Comparison of the surfaces of rat kidneys after sampling without (left) and with (right) the diaphragm pump. (d) Contour maps with streamlines simulated for sampling without (left) and with (right) the diaphragm pump. (e) Pressure distribution along the radius on the sampled surface for sampling without (left) and with (right) the diaphragm pump.