High performance wash-free magnetic bioassays through microfluidically enhanced particle specificity.

Daniel J.B Bechstein,Chin Chun Ooi,Jung-Rok Lee,Kyunglok Kim,Adi W Gani,Robert J Wilson,Shan X Wang

doi:10.1038/srep11693

Daniel J.B Bechstein, Chin Chun Ooi + Show 5 more

Open Access

https://doi.org/10.1038/srep11693

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Journal: Scientific reports	Publication Date: Jun 30, 2015
Citations: 24	License type: CC BY 4.0

Affiliation: Stanford University

Abstract

Magnetic biosensors have emerged as a sensitive and versatile platform for high performance medical diagnostics. These magnetic biosensors require well-tailored magnetic particles as detection probes, which need to give rise to a large and specific biological signal while showing very low nonspecific binding. This is especially important in wash-free bioassay protocols, which do not require removal of particles before measurement, often a necessity in point of care diagnostics. Here we show that magnetic interactions between magnetic particles and magnetized sensors dramatically impact particle transport and magnetic adhesion to the sensor surfaces. We investigate the dynamics of magnetic particles’ biomolecular binding and magnetic adhesion to the sensor surface using microfluidic experiments. We elucidate how flow forces can inhibit magnetic adhesion, greatly diminishing or even eliminating nonspecific signals in wash-free magnetic bioassays, and enhancing signal to noise ratios by several orders of magnitude. Our method is useful for selecting and optimizing magnetic particles for a wide range of magnetic sensor platforms.

Highlights

A slightly negative zeta potential are subject to a small repulsive force from slightly negatively charged sensor surfaces, significantly reducing nonspecific adhesion to the sensor[22] and improving the SNR
In our previous attempts to increase the signal in our wash free assay, larger magnetic particles have failed in open well assays due to particle adhesion on the sensor
While the washing step in our open well assay format has significantly reduced the nonspecific adhesion of larger magnetic particles, washing did not completely eliminate the adhesion and did not yield reproducible results, possibly due to extreme flow non-uniformity during crude open well washing

Summary

Introduction

A slightly negative zeta potential are subject to a small repulsive force from slightly negatively charged sensor surfaces, significantly reducing nonspecific adhesion to the sensor[22] and improving the SNR. In our previous attempts to increase the signal in our wash free assay, larger (but still sub-micron sized) magnetic particles have failed in open well assays due to particle adhesion on the sensor. More importantly, the introduction of a washing step defeats the purpose of a wash-free assay by allowing accurate measurements only after completed washing, eliminating desirable time resolved binding data This need for washing is a major drawback for many magnetic sensor platforms employing micron sized and larger particles[14]. Instead of a separate washing step used in fluid force discrimination 25,26, which is not compatible with the wash-free approach, a microfluidic assay format was chosen that allows precise control and repeatability of the applied viscous flow forces to selectively remove only nonspecifically adhered particles at the same time as delivering analyte and reagents

Methods

Results

Conclusion