Matrix assisted laser desorption/ionization mass spectrometry (MALDI MS) and MALDI MS imaging (MSI) have achieved great success in biomedical, pharmaceutical, and environmental research. However, interrogation of low-molecular-weight compounds by MALDI MS often suffers the interference from conventional organic matrix in the low mass region. In this study, we propose a negative ion MALDI MS approach for the determination of small biomolecules and MALDI MS imaging of tissue samples by using heteroatom (N, B, B/N) doped-graphene quantum dots (GQDs) synthesized by top-down strategy as an alternative matrix. Structural characterizations and performance tests revealed that the inheritance of π-conjugation system from parent graphene nanosheets and Lewis acid-base property of heteroatom doping sites play the key roles in desorption/ionization (D/I) efficiency of doped GQDs. Among the candidates, N-doped GQDs exhibited superior D/I efficiency to B-doped and B,N-codoped GQDs in negative ionization mode, in good accordance with the mechanism exploration by density functional theory calculations. This N-doped GQDs facilitated LDI MS approach allowed the detection of a wide range of small biomolecules including amino acids, fatty acids, peptides, lipids and oligosaccharides, as well as monitoring of enzymatic reactions. In addition to the high D/I efficiency, the excellent homogeneity imparted N-doped GQDs with the applicability in MALDI MSI of small biomolecules (MW&lt;500) such as amino acids, fatty acids and phosphatidic acids in a rat brain tissue slice. Furthermore, by inducing controlled cortical impact (CCI) on adult male rats, N-doped GQDs facilitated LDI MSI revealed the effect of a CCI model of traumatic brain injury (TBI) on the distribution of aforementioned low-molecular-weight metabolites. Taken together, this approach offers a new tool for acquiring the spatiotemporal information of small molecules of biological significance at sub-organ level.

Heteroatom-doped graphene quantum dots enable negative ion laser desorption ionization mass spectrometry for probing and imaging of small biomolecules

2019 Fall National Meeting

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