Breaking the Interface: Efficient Extraction of Magnetic Beads from Nanoliter Droplets for Automated Sequential Immunoassays

Droplet-based microfluidic systems offer a high potential for miniaturization and automation. Therefore, they are becoming an increasingly important tool in analytical chemistry, biosciences, and medicine. Heterogeneous assays commonly utilize magnetic beads as a solid phase. However, the sensitivit...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2020-08, Vol.92 (15), p.10283-10290
Main Authors: Metzler, Lukas, Rehbein, Ulrike, Schönberg, Jan-Niklas, Brandstetter, Thomas, Thedieck, Kathrin, Rühe, Jürgen
Format: Article
Language:English
Subjects:
Analytical chemistry
Antibodies - chemistry
Automation
Automation - methods
Beads
Biomolecules
Chemistry
Droplets
Enzyme-linked immunosorbent assay
Enzyme-Linked Immunosorbent Assay - methods
Fluorocarbons - chemistry
Hydrophobicity
Immunoassay
Immunoassays
Immunomagnetic Separation - methods
Magnetic Phenomena
Microfluidic Analytical Techniques - methods
Microfluidics
Miniaturization
Nanostructures
Reagents
Sensitivity enhancement
Sequential analysis
Solid phases
Wetting
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Summary:Droplet-based microfluidic systems offer a high potential for miniaturization and automation. Therefore, they are becoming an increasingly important tool in analytical chemistry, biosciences, and medicine. Heterogeneous assays commonly utilize magnetic beads as a solid phase. However, the sensitivity of state of the art microfluidic systems is limited by the high bead concentrations required for efficient extraction across the water–oil interface. Furthermore, current systems suffer from a lack of technical solutions for sequential measurements of multiple samples, limiting their throughput and capacity for automation. Taking advantage of the different wetting properties of hydrophilic and hydrophobic areas in the channels, we improve the extraction efficiency of magnetic beads from aqueous nanoliter-sized droplets by 2 orders of magnitude to the low μg/mL range. Furthermore, the introduction of a switchable magnetic trap enables repetitive capture and release of magnetic particles for sequential analysis of multiple samples, enhancing the throughput. In comparison to conventional ELISA-based sandwich immunoassays on microtiter plates, our microfluidic setup offers a 25–50-fold reduction of sample and reagent consumption with up to 50 technical replicates per sample. The enhanced sensitivity and throughput of this system open avenues for the development of automated detection of biomolecules at the nanoliter scale.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.0c00187