Self-Assembled Au Nanoparticle Arrays for Precise Metabolic Assay of Cerebrospinal Fluid

Abstract

Precise and rapid monitoring of metabolites in biofluids is a desirable but unmet goal for disease diagnosis and management. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) exhibits advantages in metabolite analysis. However, the low accuracy in quantification of the technique limits its transformation to clinical usage. We report herein the use of Au nanoparticle arrays self-assembled at liquid–liquid interfaces for mass spectrometry (MS)-based quantitative biofluids metabolic profiling. The two-dimensional arrays feature uniformly and closely packed Au nanoparticles with 3 nm interparticle gaps. The experimental study and theoretical simulation show that the arrays exhibit high photothermal conversion and heat confinement effects, which enhance the laser desorption/ionization efficacy. With the nanoscale roughness, the AuNP arrays as laser desorption/ionization substrates can interrupt the coffee-ring effect during droplet evaporation. Therefore, high reproducibility (RSD <5%) is obtained, enabling accurate quantitative analysis of diverse metabolites from 1 μL of biofluids in seconds. By quantifying glucose in the cerebrospinal fluid (CSF), it allows us to identify patients with brain infection and rapidly evaluate the clinical therapy response. Consequently, the method shows potential in advanced metabolite analysis and biomedical diagnostics.

Inorganic Matrices Assisted Laser Desorption/Ionization Mass Spectrometry for Metabolic Analysis in Biofluids

“…At present, most applications of noble metals in LDI MS belong to gold and silver for their highest electromagnetic field enhancement among noble metals. Wang et al [20] . used uniform two‐dimensional Au nanoparticles arrays (Figure 1a) with high photothermal conversion, heat confinement effects, and nanoscale roughness to obtain high reproducibility from glucose, arginine, and reserpine detection.…”

“…Compared to the biochemical method in the clinic, this method can reduce the required sample volume from 200 μL to 0.5 μL, and shorten the experiment time from hours to several minutes. Similarly, Wang et al [20] . applied two‐dimensional Au nanoparticle arrays with high reproducibility for quantitative analysis of glucose in CSF to evaluate brain infection and treatment efficacy.…”

Nanomaterials‐assisted metabolic analysis toward in vitro diagnostics

“…Numerous efforts have been applied to integrating nanomaterials with analytical chemical approaches for the accurate quantitation of targeted metabolite biomarkers. [ 94–105 ]…”

Nanostructured Substrates as Matrices for Surface Assisted Laser Desorption/Ionization Mass Spectrometry: A Progress Report from Material Research to Biomedical Applications

“…The same group also designed FeOOH@ZIF-8 core-satellite nanocomposite [126] and multi-shelled hollow Cr 2 O 3 spheres [127] for gynecological and schizophrenia disease diagnosis and classification respectively. Besides the above-mentioned diseases, well-designed nanostructures were also used for the diagnosis and assessment of diseases including gout, [128] osteoporosis, [129] brain infection, [130] liver cancer, [131] and type 2 diabetes mellitus. [132] Other than merely as SALDI-MS matrix, some substrates were also developed with multiple functions.…”