A Small Footprint and Robust Interface for Solid Phase Microextraction and Mass Spectrometry Based on Vibrating Sharp-Edge Spray Ionization

Abstract

Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic applications due to its simplicity, rapid analysis, and capability of reducing matrix effects for complex samples. To further promote the adoption of SPME-MS based analysis and expand its application scope calls for efficient and convenient interfaces that couple the SPME sample handling with the efficient analyte ionization for MS. Here, we report a novel interface that integrates both the desorption and the ionization steps in one device based on the capillary vibrating sharp-edge spray ionization (cVSSI) method. We demonstrated that the cVSSI is capable of nebulizing liquid samples in a pulled-tip glass capillary with a battery powered function generator. The cVSSI device allows the insertion of a SPME probe into the spray capillary for desorption and then direct nebulization of the desorption solvent in situ. With the integrated interface, we have demonstrated rapid MS analysis of drug compounds from serum samples. Quantitative determination of various drug compounds including metoprolol, pindolol, acebutolol, oxprenolol, capecitabine, and irinotecan was achieved with good linearity (R² = 0.97-0.99) and limit of detection ranging from 0.25 to 0.59 ng/mL without using a high voltage source. Only 3.5 μL of desorption solvent and 3 min desorption time were needed for the present method. Overall, we demonstrated a portable SPME-MS interface featuring high sensitivity, short analysis time, small footprint, and low cost, which makes it an attractive method for many applications requiring sample cleanup including drug compound monitoring, environmental sample analysis, and forensic sample analysis.

Figure 1.

Pictures of the portable cVSSI device. a) The overall assembly of the cVSSI device. The picture shows all the equipment that is needed for a cVSSI experiment, which includes a portable function generator, a battery, and cVSSI device. b) A close-up picture of the cVSSI device that is comprised of a piezoelectric transducer, a cover glass, and a pulled-tip capillary. c) A close-up picture of cVSSI device near the mass spectrometer. d) Plume generation by the cVSSI device. e). The image of glass capillary with the tip ID of 50 μm, scale bar = 100 μm.

Figure 2.

The complete workflow for cVSSI-SPME-MS analysis of chemicals from complex matrices. It includes 3 major steps: 1. Extraction, 2. Solvent desorption; 3. Ionization with the cVSSI.

Figure 3.

Optimization of cVSSI operation parameters. a) The frequency dependence of cVSSI spray flow rates tested on the same day. b) The frequency dependence of cVSSI spray flow rates tested on three different days for the same device. c) The amplitude dependence of cVSSI spray flow rates tested on the same day. d)The amplitude dependence of cVSSI spray flow rates tested on three different days.

Figure 4.

Quantitative performance of direct cVSSI for metoprolol. a)-c) Mass spectra of metoprolol and the internal standard carbamazepine at 0.267 ng/mL, 6.68 ng/mL, and 20.03 ng/mL, respectively. Carbamazepine concentration is fixed at 11.85 ng/mL. d) The calibration of curve of direct spray of metoprolol solutions from 0.267 ng/mL to 26.7 ng/mL with cVSSI. M1: internal standard (carbamazepine); M2: metoprolol.

Figure 5.

Optimization of SPME working conditions. a) The relationship of the signal response, S/N and the extracted volume used in the SPME, with 24 min extraction time, 3 min desorption time, and 6 μL desorption volume. b) The relationship of the signal response, S/N and extraction time with 500 μL extraction volume, 3 min desorption time, and 6 μL desorption volume. c) The relationship of the signal response, S/N and the desorption time with 500 μL extraction volume, 24 min extraction time, and 6 μL desorption volume. d) The relationship of the signal response, S/N and the desorption volume with 500 μL extraction volume, 30 min extraction time, and 3 min desorption time. The signal response is the ratio of the ion intensity of the analyte peak to the intensity of the internal standard.

Figure 6.

Quantitative determination of concentrations of β-blockers in serum samples. a) The extracted linear curve of metoprolol in serum from 0.267 ng/mL to 26.7 ng/mL and b) 0.534 ng/mL to 5.34 ng/mL. c) The extracted linear curve of pindolol in serum in the range from 0.249 ng/mL to 24.9 ng/mL. and d) The extracted linear curve of a mixture containing metoprolol and pindolol in serum from 0.249 to 26.7 ng/mL.