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.
Our sense of smell relies on sensitive, selective atomic-scale processes that are initiated when a scent molecule meets specific receptors in the nose. However, the physical mechanisms of detection are not clear. While odorant shape and size are important, experiment indicates these are insufficient. One novel proposal suggests inelastic electron tunneling from a donor to an acceptor mediated by the odorant actuates a receptor, and provides critical discrimination. We test the physical viability of this mechanism using a simple but general model. Using values of key parameters in line with those for other biomolecular systems, we find the proposed mechanism is consistent both with the underlying physics and with observed features of smell, provided the receptor has certain general properties. This mechanism suggests a distinct paradigm for selective molecular interactions at receptors (the swipe card model): recognition and actuation involve size and shape, but also exploit other processes. * Electronic address: j.brookes@ucl.ac.uk † Electronic address: to˙milaraki@hotmail.com ‡ Electronic address: a.horsfield@ucl.ac.uk § Electronic address: a.stoneham@ucl.ac.uk 1 Our sense of smell affects our behavior profoundly. Discrimination between small molecules, often in very low concentrations, allows us to make judgments about our immediate environment[1] and influence our perceptions. Even though odorants are key components of many commercial products [2], the biomolecular processes of olfaction are inadequately understood: scent design is not straightforward. We know that odor detection involves several types of receptor for a given odorant, and understand how a receptor signal is amplified and processed [3,4]. However, the initial selective atomic-scale processes as the scent molecule meets its nasal receptors are not well understood. Odorant shape and size are certainly important, but experiment shows these are insufficient. Here we assess the novel proposal that a critical early step involves inelastic electron tunneling mediated by the odorant. We test the physical viability of this mechanism[5] using electron transfer (ET) theory, with values of key parameters in line with those for other biomolecular systems. The proposed mechanism is viable (there are no physics-based objections and is consistent with known features of olfaction) provided the receptor has certain general properties. This mechanism has wider importance because it introduces a distinct paradigm for selective actuation of receptors: whereas lock and key models[6] imply size, shape and non-bonding interactions (the docking criteria) are all, in our swipe card model recognition and actuation involve other processes in addition to docking. Thus it encompasses and goes beyond mechanisms such as proton transfer, discussed by us previously [7].All current theories agree that selective docking of odorants is important [2]. However, odorants are small molecules (rarely more than a few tens of atoms[2]), and it is improbable that docking criteria...
Chlorosomes are likely the largest and most efficient natural light-harvesting photosynthetic antenna systems. They are composed of large numbers of bacteriochlorophylls organized into supramolecular aggregates. We explore the microscopic origin of the fast excitation energy transfer in the chlorosome using the recently resolved structure and atomistic-detail simulations. Despite the dynamical disorder effects on the electronic transitions of the bacteriochlorophylls, our simulations show that the exciton delocalizes over the entire aggregate in about 200 fs. The memory effects associated to the dynamical disorder assist the exciton diffusion through the aggregates and enhance the diffusion coefficients as a factor of 2 as compared to the model without memory. Furthermore, exciton diffusion in the chlorosome is found to be highly anisotropic with the preferential transfer toward the baseplate, which is the next functional element in the photosynthetic system.
Phototrophic organisms such as plants, photosynthetic bacteria and algae use microscopic complexes of pigment molecules to absorb sunlight. Within the light-harvesting complexes, which frequently have several functional and structural subunits, the energy is transferred in the form of molecular excitations with very high efficiency. Green sulfur bacteria are considered to be amongst the most efficient light-harvesting organisms. Despite multiple experimental and theoretical studies of these bacteria the physical origin of the efficient and robust energy transfer in their lightharvesting complexes is not well understood. To study excitation dynamics at the systems level we introduce an atomistic model that mimics a complete light-harvesting apparatus of green sulfur bacteria. The model contains approximately 4000 pigment molecules and comprises a double wall roll for the chlorosome, a baseplate and six Fenna-Matthews-Olson trimer complexes. We show that the fast relaxation within functional subunits combined with the transfer between collective excited states of pigments can result in robust energy funneling. Energy transfer is robust on the initial excitation conditions and temperature changes. Moreover, the same mechanism describes the coexistence of multiple timescales of excitation dynamics frequently observed in ultrafast optical experiments. While our findings support the hypothesis of supertransfer, the model reveals energy transport through multiple channels on different length scales.
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