Zwitterionic sulfobetaine-based hypercrosslinked hydrophilic materials for bioanalysis

Analysis of bioactive polar molecules is crucial for different fields, including biology, clinic medicine, and separation science. However, the design of the separation materials remains a huge challenge due to their tedious preparation process and limited chromatographic performances of traditional hydrophilic materials. New-generation hydrophilic polymer materials prepared via a sole-monomer system exhibit excellent reproducibility and chromatographic efficiency; however, such polymers reported to date have a high swelling propensity and risk of low surface exposure of functional groups, which limit their application as separation materials. In this study, N,N-bis(methacryloxyethyl)-N-methyl-N-(3-sulfopropyl)ammonium betaines (BMMSB), a zwitterionic sulfobetaine, was used to rapidly fabricate the zwitterionic hypercrosslinked hydrophilic polymer materials via the sole-monomer system. The novel hypercrosslinked hydrophilic materials exhibited high porosity and permeability, superhydrophilicity, low protein adsorption, and excellent capillary column efficiency (up to 134,950 plates/m for thiourea). It was able to enrich 28 N-glycopeptides from hIgG tryptic digests with a higher efficiency than that of traditional poly(SPE-co-EDMA) monolith and commercial ZIC-HILIC materials. Additionally, the polyBMMSB hydrophilic materials demonstrated superior selectivity and column efficiency to the poly(SPE-co-EDMA) monolith for the separation of various small bioactive molecules, including nucleobases and nucleosides, phenol derivatives, benzoic acid derivatives, urea and allantoin. Especially, high performance bioanalysis of Alzheimer's disease biomarkers plasma Aβ42 and Aβ40, or some steroid hormones in human plasma were also achieved by the polyBMMSB monolith combined with nano liquid chromatography-mass spectrometry. As such, these sulfobetaine-based zwitterionic polymers may serve as a prototypical next-generation zwitterionic hydrophilic materials for rapid and efficient bioanalysis.