Smart sampling as the “Spot‐on” Method for LC‐MS protein analysis from dried blood spots

Abstract

This perspective explores the feasibility of smart sampling with dried blood spots for the determination of proteins and peptides from human biomatrices using liquid chromatography coupled to mass spectrometry for clinical purposes. The focus is on innovative approaches to transform filter paper from a mere sample carrier to an active element in sample preparation, with the aim of reducing the need for extensive and intensive sample preparation in the conventional sense. Specifically, we discuss the use of modified cellulose to integrate sample preparation at an early stage of sample handling. The use of paper immobilized with either trypsin or monoclonal antibodies for protein digestion and affinity clean‐up is discussed as a potential benefit of starting sample preparation instantly at the moment of sampling to optimize time efficiency and enable faster analysis, diagnosis, and follow‐up of patients.

Advancements in clinical approaches, analytical methods, and smart sampling for LC–MS‐based protein determination from dried matrix spots

“…There is a handful of review articles and perspectives covering specifically LC-MS-based protein determination from DBS and other dried biological matrices [14][15][16][17][18][19][20]. The reviews of both Nakajima et al [18] and Lehmann et al [20] mainly discuss the use of DBS in clinical applications.…”

“…In their conclusions it is stated that DBS has the potential to become as useful as liquid blood samples, revolutionizing the field of clinical biochemistry [20,21]. In other reviews [15][16][17]19] the horizon is expanded to new frontiers within LC-MS-based protein determination from DBS. The potential of modifying the sampling device or the material of which the samplers are made is highlighted here.…”

“…Because of F I G U R E 6 Comparison between smart affinity sampling-these samplers have immobilized mAbs on the surface to capture target proteins (upper part) and the conventional workflow (lower part) for targeted protein determination from DBS. Source: With permission reproduced from Johannsen et al [16].…”

One‐step functionalization of paper and simplified antibody immobilization for on‐the‐spot immunocapture from dried serum in liquid chromatography‐tandem mass spectrometry based targeted protein determination

“…This concept is known as smart sampling, and the idea is to let the sample preparation start at the moment of sampling, thus reducing the workload needed prior to analysis. 17,18 Skjaervø et al were the first to integrate trypsin digestion into paper-based sampling to reduce the workload associated with MS-based protein analysis from DBS samples. 19 These trypsin reactors were initially made by dripping trypsin immobilized on polymer beads onto paper samplers.…”

“…A way to combat the low sample throughput is to integrate certain sample preparation steps onto the paper sampler. This concept is known as smart sampling , and the idea is to let the sample preparation start at the moment of sampling, thus reducing the workload needed prior to analysis 17,18 . Skjærvø et al were the first to integrate trypsin digestion into paper‐based sampling to reduce the workload associated with MS‐based protein analysis from DBS samples 19 .…”