Journal
ACS NANO
Volume 12, Issue 1, Pages 279-288Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b06229
Keywords
lateral flow immunoassay; porous platinum core-shell nanoparticles; broad dynamic range; enzyme mimic; nanobodies; biorthogonal chemistry; point-of-care; HIV detection
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Funding
- i-sense Engineering and Physical Sciences Research Council (EPSRC) IRC in Early Warning Sensing Systems for Infectious Diseases [EP/K031953/1]
- Medical Research Council (MRC) grant m-Africa [MR/P024378/1]
- Marshall Aid Commemoration Commission
- ERC Seventh Framework Programme Consolidator grant Naturale CG [616417]
- EPSRC grant Bio-functionalised nanomaterials for ultrasensitive biosensing [EP/K020641/1]
- Royal Society Wolfson Research Merit Award
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- UCL studentship
- EPSRC [EP/M01792X/1]
- EPSRC [EP/K031953/1, EP/K020641/1] Funding Source: UKRI
- MRC [MR/P024378/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/K031953/1, EP/K020641/1] Funding Source: researchfish
- Medical Research Council [MR/P024378/1] Funding Source: researchfish
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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.
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