Microscale solid-phase extraction: advances in sorbent formats, system design, integration, and detection methods.

Abstract

Sample preparation is essential in chemical analysis as a critical determinant of analytical sensitivity, selectivity, and throughput, and is often the most resource-intensive stage of an analytical workflow. Microscale solid-phase extraction (µSPE) helps to address the sample preparation limitations associated with conventional SPE by enabling analyte enrichment and matrix cleanup at reduced volumes, with integration potential that traditional formats cannot match. This Critical Review assesses recent advances across six µSPE modalities: reverse-phase, ion exchange, immunoaffinity, aptamer-based, nucleic acid affinity, and magnetic particle, with attention to device preparation, detection integration, and performance metrics of each platform. Key enabling technologies for advancing µSPE, such as 3D printing, are described, and notable trends in the field are identified. Additionally, significant opportunities for future development in µSPE are discussed. Ongoing work positions µSPE as a foundational technology for advancing sample preparation and enhancing chemical analysis reliability.