Labels with magneto-plasmonic properties for immunodiagnostics fabricated by nano-imprint-lithography

LAMPION develops novel multifunctional nanoparticles with hybrid magnetic and plasmon-optical properties and their application as nanoprobes for immunodiagnostics. Objective is a demonstrating assay to detect NTproCNP, a clinically relevant biomarker for the pregnancy disorder pre-eclampsia.

The objective of LAMPION is the development of novel multifunctional nanoparticles with hybrid magnetic and plasmon-optical properties and their application as nanoprobes for immunodiagnostics. The innovative breakthrough is the reliable fabrication of such hybrid nanoparticles by thin film technology and nanoimprint lithography, and their transformation into immuno-sensing nanoprobes via biofunctionalization. By applying them as probes for an innovative homogeneous immunodiagnostic method based on optical analysis of the hybrid biofunctional nanoparticles, early point-of-care pregnancy disorder screening will be demonstrated.

Depicted as nano-scale laboratories, the nanoprobes will fulfill several functions. The biofunctionalized surface forms a reaction zone for the specific target biomolecules. The magnetically activated movement is an indicator of biomolecule binding, and the plasmon supported anisotropic shape functions as optical antenna for signal transmission in the event of binding. The overall concept comprises careful design and execution of several consecutive nanofabrication and biofunctional nano-surface engineering steps that generate a nanotechnology-driven added value to point-of-care detection of biomarkers at previously unattainably low limit of detection (LoD) levels. The nanoprobes utilize effects only present at the nano-level, i.e. photonic signal enhancement by localized surface plasmons, biomolecular recognition by the lock-and-key binding principle and sizeable changes in hydrodynamic nanoprobe properties on binding of analyte molecules.

Further objective is the application of these nanoprobes in a demonstrating assay to detect NTproCNP, a clinically relevant biomarker for the pregnancy disorder pre-eclampsia, which currently cannot be diagnosed at the point-of-care due to its low concentration. Compared to previous results obtained by chemically synthesized nanoparticle probes, detection of NTproCNP will require to improve the LoD of this immunodiagnostic method by about three orders of magnitude. Here, it is expected to achieve at least two orders of magnitude LoD enhancement by the hybrid magnetic and plasmon-optical properties of the physically structured nanoparticles, while at least another order of magnitude LoD enhancement is anticipated by performing enhanced optical analysis of an optimized nanoprobe-based NTproCNP assay within a newly developed cartridge. The nanoprobes will be integrated into a microfluidic cartridge with superior optical properties which lays the foundation for a nanotechnology-based diagnostic product with high market potential.

The results of LAMPION will pave the way to earlier and more thorough diagnostics of pre-eclampsia by enabling point-of-care testing of NTproCNP and - due to the universal character of the hybrid nanoparticles - of many more low-abundance biomarkers for other diseases.