Numerical Modelling of the Optical Properties of Plasmonic and Latex Nanoparticles to Improve the Detection Limit of Immuno-Turbidimetric Assays

Abstract

Turbidimetric assays with latex nanoparticles are widely applied for the detection of biological analytes, because of their rapidity, low cost, reproducibility, and automatization. However, the detection limit can be lowered only at the price of a reduced dynamic range, due to the rapid saturation of the light scattering signal at high analyte concentration. Here, we use numerical calculations to investigate the possibility of increasing the performance of immuno-turbidimetric assays without compromising the measurement dynamic range, by combining plasmonic (gold, silver) and latex nanoparticles. Our modelling results show that plasmonic nanoparticles are compatible with a large signal change even when small aggregates are formed, i.e., at low analyte concentration. The working principle relies on the remarkable modification of the surface plasmon band when noble metal nanoparticles form oligomers, and also when latex particles are included in the aggregate. At high analyte concentration, when larger aggregates form, the latex particles can provide the required linear response of standard immuno-turbidimetric assays. Thus, the combination of the two components can be a successful strategy to improve the detection limit and the dynamic range, while maintaining all the advantages of the homogeneous immuno-turbidimetric assays.

Plasmonic Absorption in Antigen-Induced Aggregated Gold Nanoparticles: Toward a Figure of Merit for Optical Nanosensors

“…The interparticle distance has crucial importance for the optical properties of Au NP aggregates, but the complex fractal structure and the variety of interparticle distances do not allow for an easy prediction of the resulting optical properties of the immunocomplexes just from TEM images. Thus, the DDA method ,, was used to accurately reproduce the position and shape of Au NPs in the aggregates (Figure D) and calculate the corresponding extinction cross-section (σ ext , see the Materials and Methods section and the Supporting Information for details). It should be noted that the TEM images provide a 2D projection of 3D objects embedded in the polymeric matrix after water evaporation and that the interparticle distance in the actual solution may be different (likely larger) than that in the dried PVA matrix; hence, the DDA simulations are just a first approximation of the expected extinction profiles for the corresponding tridimensional immunocomplexes in the colloidal solution.…”

“…The effect of the water solvent was accounted for by setting the refractive index of the nonabsorbing matrix to 1.334. The complex dielectric constant of Au was obtained from ref and corrected for the intrinsic size effects according to what was described in refs , and .…”

Consistency Analysis of 3 Detection Systems for Measuring Serum C-Reactive Protein

“…Clinical chemistry analyzers based on turbidimetric principles are used in large clinical settings, while commercially approved ELISA kits are preferred in dispersed and remote settings [ 9 ]. In the present study, the Mindray BC-5390, Mindray BC-6800, and Johnson Vitros5600 analyzers were based on the principle of the turbidimetric method to detect CRP value [ 10 , 28 ]. The difference was that the Mindray analyzers used immunity transmission turbidity, while the Johnson Vitros5600 analyzer used immune scatter turbidity.…”

Antibody-Conjugated Nanodiamonds as Dual-Functional Immunosensors for In Vitro Diagnostics

“…PETIA is one of the homogeneous immunoassays well adopted in clinical research . The assay typically uses monodisperse latex beads of 100–200 nm in diameter to enhance light-scattering signals due to aggregation of the antibody-conjugated particles in the presence of target antigens in a sandwich configuration. − Sample concentrations of 0.5 mg/L or less have been measured with good precision and high reproducibility. Compared with other commonly used immunodiagnostic methods such as enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay (LFIA), PETIA has several distinct advantages such as rapid (within 10 min), simple (single-step and washing-free), reproducible (small coefficient of variation), and automatable .…”