Small Molecule Ambient Mass Spectrometry Imaging by Infrared Laser Ablation Metastable-Induced Chemical Ionization

Abstract

Presented here is a novel ambient ion source termed infrared laser ablation metastable-induced chemical ionization (IR-LAMICI). IR-LAMICI integrates IR laser ablation and direct analysis in real time (DART)-type metastable-induced chemical ionization for open air mass spectrometry (MS) ionization. The ion generation in the IR-LAMICI source is a two step process. First, IR laser pulses impinge the sample surface ablating surface material. Second, a portion of ablated material reacts with the metastable reactive plume facilitating gas-phase chemical ionization of analyte molecules generating protonated or deprotonated species in positive and negative ion modes, respectively. The successful coupling of IR-laser ablation with metastable-induced chemical ionization resulted in an ambient plasma-based spatially resolved small molecule imaging platform for mass spectrometry (MS). The analytical capabilities of IR-LAMICI are explored by imaging pharmaceutical tablets, screening counterfeit drugs, and probing algal tissue surfaces for natural products. The resolution of a chemical image is determined by the crater size produced with each laser pulse but not by the size of the metastable gas jet. The detection limits for an active pharmaceutical ingredient (acetaminophen) using the IR-LAMICI source is calculated to be low picograms. Furthermore, three-dimensional computational fluid dynamic simulations showed improvements in the IR-LAMICI ion source are possible.

Surface analysis of lipids by mass spectrometry: More than just imaging

“…Additionally, the use of IR laser desorption coupled with DART has also been described for enhanced resolution (~300 µm) during imaging experiments [240]. While several possible ionization mechanisms have been proposed, the dominant ion forming pathway is believed to occur via interaction of metastable helium with atmospheric components such as water and 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 44 oxygen [15].…”

Sensitivity “Hot Spots” in the Direct Analysis in Real Time Mass Spectrometry of Nerve Agent Simulants

“…Despite the wide adoption of DART as a high-throughput screening tool for pharmaceuticals [5][6][7], homeland security [8][9][10][11], metabolomics [12,13], and polymer analysis [14,15], the fundamental variables that affect DART analysis are still under investigation. The ionization region in DART MS is a dynamic environment involving complex fluid dynamics, steep temperature gradients, and weak electrostatic fields that are a result of the ion source geometry, sample position and orientation, and instrumental settings [16].…”

Analysis of pharmaceutical products and herbal medicines using ambient mass spectrometry

“…Both infrared laser ablation metastable-induced chemical ionization (IR-LAMICI) [146] and plasma assisted laser desorption ionization (PALDI) [147] are the APCI-based ambient ionization techniques integrated laser desorption and metastable-induced chemical ionization, and the ionization process is taken place when the heated metastable plasma contacts the analyte molecules desorbed by the pulse laser. The difference between IR-LAMICI and PALDI is the wavelength of laser, and IR-LAMICI uses a mid-infrared laser at wavelength of 2.94 μm while PALDI uses a 355, 532, and 1064 nm multi-wavelength laser to ablate the sample surface for desorption of analytes.…”

“…Both IR-LAMICI and PALDI process the performance of surface imaging, and they were applied to image the active pharmaceutical ingredients in pharmaceutical products and herbal medicines. For example, acetaminophen in Tyleno tablet was imaged by IR-LAMICI-MS [146] with a resolution of ~300 μm was obtained. Baicalein and wogonin in herbal medicines of Radix Scutellariae were imaged by PALDI-MS with an excellent spatial resolution of 60 μm, and baicalein and wogonin were observed to concentrate at the epidermis of the root and at the edge of the vascular cylinder [147].…”