ACS nano 2017 12 07() doi 10.1021/acsnano.7b06229
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 timeframes of PoC testing. To address this, we developed a serum-stable, nanoparticle catalyst-labelled 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 establish 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 minutes. 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 non-communicable diseases, and can be capitalized upon in PoC settings for early disease detection.