High-Throughput Analysis of the Plasma N-Glycome by UHPLC

Methods Mol Biol. 2017:1503:97-108. doi: 10.1007/978-1-4939-6493-2_8.

Abstract

The understanding of glycosylation alterations in health and disease has evolved significantly and glycans are considered to be relevant biomarker candidates. High-throughput analytical technologies capable of generating high-quality, large-scale glycoprofiling data are in high demand. Here, we describe an automated sample preparation workflow and analysis of N-linked glycans from plasma samples using hydrophilic interaction liquid chromatography with fluorescence detection on an ultrahigh-performance liquid chromatography (UHPLC) instrument. Samples are prepared in 96-well plates and the workflow features rapid glycoprotein denaturation, enzymatic glycan release, glycan purification on solid-supported hydrazide, fluorescent labeling, and post-labeling cleanup with solid-phase extraction. The development of a novel approach for plasma N-glycan analysis and its implementation on a robotic platform significantly reduces the time required for sample preparation and minimizes technical variation. It is anticipated that the developed method will contribute to expanding high-throughput capabilities to analyze protein glycosylation.

Keywords: Automation; Glycan analysis; High-throughput; N-linked glycosylation; Plasma; Robotics; Ultrahigh-performance liquid chromatography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods*
  • Equipment Design
  • Glycomics / instrumentation
  • Glycomics / methods*
  • Glycoproteins / blood
  • Glycoproteins / chemistry*
  • Glycoproteins / isolation & purification
  • Glycosylation
  • High-Throughput Screening Assays / instrumentation
  • High-Throughput Screening Assays / methods
  • Humans
  • Plasma / chemistry
  • Polysaccharides / analysis*
  • Polysaccharides / blood
  • Polysaccharides / isolation & purification
  • Protein Denaturation
  • Software
  • Solid Phase Extraction / instrumentation
  • Solid Phase Extraction / methods

Substances

  • Glycoproteins
  • Polysaccharides