N-Doped Graphene: An Alternative Carbon-Based Matrix for Highly Efficient Detection of Small Molecules by Negative Ion MALDI-TOF MS

Abstract

Gas-phase N-doped graphene (gNG) was synthesized by a modified thermal annealing method using gaseous melamine as nitrogen source and then for the first time applied as a matrix in negative ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for small molecule analysis. Unlike the complicated adducts produced in positive ion mode, MS spectra obtained on gNG matrix in negative ion mode was only featured by deprotonated molecule ion peaks without matrix interference. By the gNG assisted desorption/ionization (D/I) process, some applications were carried out on a wide range of low-molecular weight (MW) analytes including amino acids, fatty acids, peptides, anabolic androgenic steroids as well as anticancer drugs, with an extraordinary laser desorption/ionization (LDI) efficiency over traditional α-cyano-4-hydroxycinnamic acid (CHCA) and other carbon-based materials in the negative ion detection mode. By comparison of a series of graphene-based matrixes, two main factors of matrix gNG were unveiled to play a decisive role in assisting negative ion D/I process: a well-ordered π-conjugated system for laser absorption and energy transfer; pyridinic-doped nitrogen species functioning as deprotonation sites for proton capture on negative ionization. The good salt tolerance and high sensitivity allowed further therapeutic monitoring of anticancer drug nilotinib in the spiked human serum, a real case of biology. Signal response was definitely obtained between 1 mM and 1 μM, meeting the demand of assessing drug level in the patient serum. This work creates a new application branch for nitrogen-doped graphene and provides an alternative solution for small molecule analysis.

Screening of Toxic Chemicals in a Single Drop of Human Whole Blood Using Ordered Mesoporous Carbon as a Mass Spectrometry Probe

“…43−45 Furthermore, unmodified ordered mesoporous carbon plays multiple roles in the analysis and thereby eliminates the use of other materials, making the method more facile than previously reported methods. 18,35 Screening of Toxic Chemicals in Worker Whole Blood Samples. We applied the as-proposed method in identification and screening of toxic chemicals in whole blood samples collected from workers in a perfluorochemical plant.…”

Recent progress in application of carbon nanomaterials in laser desorption/ionization mass spectrometry

“…To enhance the LDI efficiency (e.g., N-doping [87] and modification with SA [88]) 2. To improve the selectivity of the SELDI probe [89][90][91] 3.…”

Humic acids as both matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and adsorbent for magnetic solid phase extraction

“…were also employed to reduce the matrix interference in the mass region of interest. Taking advantages of the efficient desorption/ionization ability, carbon-based materials like fullerene, graphite, carbon nanotubes (CNTs), graphene (G) as well as its oxydum like oxidized carbon nanotubes (OCNTs) and graphene oxide (GO) have drawn considerable attention and been regarded as powerful and promising matrices for the MALDI-MS analysis of small molecules because of their remarkable charge mobility and universal optical absorption property [8,27]. Nevertheless, there are still some limitations for these carbon-based species as MALDI matrix, for example, low solubility, matrix interference at high laser power, problems with metallic impurities and poor adsorption on MALDI target surfaces [4,9].…”

“…Nevertheless, there are still some limitations for these carbon-based species as MALDI matrix, for example, low solubility, matrix interference at high laser power, problems with metallic impurities and poor adsorption on MALDI target surfaces [4,9]. Although several approaches like material immobilization, film construction, and hydrophilic modification were adopted to eliminate these limitations [4,27], the additional processing could aggravate the complexity of manipulation to some extent. Thus, the novel MALDI matrix material suitable for detection of small molecule remains to be developed.…”