Paper-based
lateral flow immunoassays (LFIAs) are one of the most
widely used point-of-care (PoC) devices; however, their application
in early disease diagnostics is often limited due to insufficient
sensitivity for the requisite sample sizes and the short time frames
of PoC testing. To address this, we developed a serum-stable, nanoparticle
catalyst-labeled LFIA with a sensitivity surpassing that of both current
commercial and published sensitivities for paper-based detection of
p24, one of the earliest and most conserved biomarkers of HIV. We
report the synthesis and characterization of porous platinum core–shell
nanocatalysts (PtNCs), which show high catalytic activity when exposed
to complex human blood serum samples. We explored the application
of antibody-functionalized PtNCs with strategically and orthogonally
modified nanobodies with high affinity and specificity toward p24
and established the key larger nanoparticle size regimes needed for
efficient amplification and performance in LFIA. Harnessing the catalytic
amplification of PtNCs enabled naked-eye detection of p24 spiked into
sera in the low femtomolar range (ca. 0.8 pg·mL–1) and the detection of acute-phase HIV in clinical
human plasma samples in under 20 min. This provides a versatile absorbance-based
and rapid LFIA with sensitivity capable of significantly reducing
the HIV acute phase detection window. This diagnostic may be readily
adapted for detection of other biomolecules as an ultrasensitive screening
tool for infectious and noncommunicable diseases and can be capitalized
upon in PoC settings for early disease detection.
Recent advances in nanomedicine have shown that dramatic improvements in nanoparticle therapeutics and diagnostics can be achieved through the use of disease specific targeting ligands.
Enabling oriented installation of non-engineered antibody fragments on nanoparticle surfaces to create next-generation antibody–nanoparticle conjugates.
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