Graphene Oxide Derivatives and Their Nanohybrid Structures for Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Analysis of Small Molecules

Abstract

Matrix-assisted laser desorption/ionization (MALDI) has been considered as one of the most powerful analytical tools for mass spectrometry (MS) analysis of large molecular weight compounds such as proteins, nucleic acids, and synthetic polymers thanks to its high sensitivity, high resolution, and compatibility with high-throughput analysis. Despite these advantages, MALDI cannot be applied to MS analysis of small molecular weight compounds (<500 Da) because of the matrix interference in low mass region. Therefore, numerous efforts have been devoted to solving this issue by using metal, semiconductor, and carbon nanomaterials for MALDI time-of-flight MS (MALDI-TOF-MS) analysis instead of organic matrices. Among those nanomaterials, graphene oxide (GO) is of particular interest considering its unique and highly tunable chemical structures composed of the segregated sp² carbon domains surrounded by sp³ carbon matrix. Chemical modification of GO can precisely tune its physicochemical properties, and it can be readily incorporated with other functional nanomaterials. In this review, the advances of GO derivatives and their nanohybrid structures as alternatives to organic matrices are summarized to demonstrate their potential and practical aspect for MALDI-TOF-MS analysis of small molecules.

Keywords: graphene oxide; laser desorption/ionization; mass spectrometry; nanocomposite; surface functionalization.

Figure 1

(a) A schematic diagram of size-fractionalization of GO flakes depending on their lateral of dimension. (b) LDI-TOF-MS spectra of small molecules obtained by using size-fractionalized GO flakes. Adapted with permission from ref. [64]. Copyright 2015 Wiley-VCH.

Figure 2

Schematic diagrams of (a) the separation process of OD and bwGO from aGO by washing with 0.1 M NaOH, and (b) LDI-TOF-MS analysis process of the obtained aGO and bwGO. (c) LDI-TOF-MS spectra of aGO and bwGO. The symbol @ in blue color corresponds to the carbon cluster ions and the symbol # in red color corresponds to the oxidized carbon cluster ions. Adapted from ref. [66] with permission from The Royal Society of Chemistry.

Figure 3

LDI-TOF-MS spectra of small molecules such as glucose, sorbitol, sucrose, arginine, histidine, and phenylalanine obtained with aGO and bwGO. Reproduced with permission from ref. [67]. Copyright (2019) Japan Society for Analytical Chemistry.

Figure 4

(a) Fabrication processes and (b) scanning electron microscopy (SEM) images of GO, RGO, MWCNT-NH₂, RGO/MWCNT, GO/MWCNT-NH₂ and RGO/MWCNT-NH₂ nanohybrid films. (c) The relative mass signal intensities of various small molecules such as cellobiose, Leu-enkephalin, Fmoc-Lys(Boc)-OH, phenylalanine, glucose, lysine, D-mannitol and GGDEVDSG peptide. Adapted with permission from ref. [71]. Copyright 2011 American Chemical Society.

Figure 5

(a) Fabrication process, (b) UV-Vis absorption spectra, (c) surface roughness and (d) ellipsometric thickness of GO and MWCNT-NH₂ nanohybrid films prepared with the different number of LBL assembly cycles. Adapted with permission from ref. [72]. Copyright 2012 American Chemical Society.

Figure 6

(a) Preparation process of Au NPs/PAAH-GO films and (b) LDI-TOF-MS analysis process of small molecules on Au NPs/PAAH-GO films. (c) LDI-TOF-MS spectra of small molecules such as glucose, mannitol, cellobiose, phenylalanine, glutamine and Leu-enkephalin obtained on Au NPs/PAAH-GO films. Adapted with permission from ref. [82]. Copyright 2012 American Chemical Society.

Figure 7

Preparation process and structure of Ag NPs/RGO nanohybrid films, and their application to LDI-TOF-MS analysis of small molecules. Reproduced from ref. [86] with permission from The Royal Society of Chemistry.

Figure 8

(a) Schematic diagram of the structure and LDI-TOF-MS application of ZnO/RGO nanohybrid structures. (b) LDI-TOF-MS spectra and (c) standard concentration curve of B[a]P obtained with ZnO/RGO nanohybrid structures with different concentration. Adapted with permission from ref. [93]. Copyright (2018) Elsevier.