Abstract
We demonstrate a homogeneous biosensor for the detection of multivalent targets by combination of magnetic nanoparticle (MNP) chains and a low-cost 405nm laser-based optomagnetic system. The MNP chains are assembled in a rotating magnetic field and stabilized by multivalent target molecules. The number of chains remaining in zero field is proportional to the target concentration, and can be quantified by optomagnetic measurements. The shape anisotropy of the MNP chains enhances the biosensor system in terms of providing efficient mixing, reduction of depletion effects (via magnetic shape anisotropy), and directly increasing the optomagnetic signal (via optical shape anisotropy). We achieve a limit of detection (LOD) of 5.5pM (0.82ng/mL) for the detection of a model multivalent molecule, biotinylated anti-streptavidin, in PBS. For the measurements of prostate-specific antigen (PSA) in 50% serum using the proposed method, we achieve an LOD of 21.6pM (0.65ng/mL) and a dynamic detection range up to 66.7nM (2µg/mL) with a sample-to-result time of approximately 20min. The performance for PSA detection therefore well meets the clinical requirements in terms of LOD (the threshold PSA level in blood is 4ng/mL) and detection range (PSA levels span from < 0.1–104ng/mL in blood), thus showing great promise for routine PSA diagnostics and for other in-situ applications.
Highlights
Due to their large surface-to-volume ratio, simplicity of biofunctionalization, low background signal in biological samples, and cost-efficiency, magnetic particles have been widely used in biosensors ranging from in-situ decentralized diagnostics to centralized laboratory based high-throughput assays (Lee et al, 2015; Tekin and Gijs, 2013)
In the absence of multivalent target molecules, the magnetic chains quickly dissociate during the optomagnetic measurement and correspondingly the optomagnetic spectrum contains only the signal from unbound magnetic nanoparticle (MNP)
Our method allows for the simultaneous detection of MNP chains and unbound MNPs
Summary
Due to their large surface-to-volume ratio, simplicity of biofunctionalization, low background signal in biological samples, and cost-efficiency, magnetic particles have been widely used in biosensors ranging from in-situ decentralized diagnostics to centralized laboratory based high-throughput assays (Lee et al, 2015; Tekin and Gijs, 2013). The relationship between the concentration of multivalent molecules and the shape anisotropy of the chains has been utilized to design RMF-based biosensors (Park et al, 2010a, 2010b; Ranzoni et al, 2011; Vuppu et al, 2004). Some other important properties of the suspension, such as the hydrodynamic size of the chains and the concentration of unbound magnetic particles, were not monitored due to the design of the sensors and the utilization of superparamagnetic particles These optomagnetic biosensors have limited linear detection ranges (no more than 3 orders of magnitude) and lack the potential for multiplexing. Both of these works only demonstrated the capability of their biosensors with biotin-avidin/streptavidin model reaction systems, which are much stronger and faster than common biological reactions
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