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.

Despite certain quantum concepts, such as superposition states, entanglement, 'spooky action at a distance' and tunnelling through insulating walls, being somewhat counterintuitive, they are no doubt extremely useful constructs in theoretical and experimental physics. More uncertain, however, is whether or not these concepts are fundamental to biology and living processes. Of course, at the fundamental level all things are quantum, because all things are built from the quantized states and rules that govern atoms. But when does the quantum mechanical toolkit become the best tool for the job? This review looks at four areas of 'quantum effects in biology'. These are biosystems that are very diverse in detail but possess some commonality. They are all (i) effects in biology: rates of a signal (or information) that can be calculated from a form of the 'golden rule' and (ii) they are all protein-pigment (or ligand) complex systems. It is shown, beginning with the rate equation, that all these systems may contain some degree of quantum effect, and where experimental evidence is available, it is explored to determine how the quantum analysis aids in understanding of the process.

We present a theoretical study of excitation dynamics in the chlorosome antenna complex of green photosynthetic bacteria based on a recently proposed model for the molecular assembly. Our model for the excitation energy transfer (EET) throughout the antenna combines a stochastic time propagation of the excitonic wave function with molecular dynamics simulations of the supramolecular structure, and electronic structure calculations of the excited states. We characterized the optical properties of the chlorosome with absorption, circular dichroism and fluorescence polarization anisotropy decay spectra. The simulation results for the excitation dynamics reveal a detailed picture of the EET in the chlorosome. Coherent energy transfer is significant only for the first 50 fs after the initial excitation, and the wavelike motion of the exciton is completely damped at 100 fs. Characteristic time constants of incoherent energy transfer, subsequently, vary from 1 ps to several tens of ps. We assign the time scales of the EET to specific physical processes by comparing our results with the data obtained from time-resolved spectroscopy experiments.

The olfactory system sensitively discerns scents from many small molecules as the brain analyses signals from nasal receptors. These receptors are selective to some degree, though the mechanism for selectivity is still controversial. Enantiomers, chiral pairs of left-and right-handed structures, are an important class of molecules in assessing proposed mechanisms. We show that there is a correlation between molecular (structural) flexibility and whether or not the left-and right-handed enantiomers smell the same. In particular, for the fairly extensive class of enantiomers with six-membered ring flexibility, enantiomers do not smell the same. There are, of course, significant experimental uncertainties, which we discuss here. We discuss models of receptor selectivity, both those based on shape and those where discrimination is based on other factors, such as electron affinity, proton affinity or vibration frequencies. The differences in scent of these enantiomers appear to be consistent with simple generalizations of a 'swipe card' model in which, while the shape must be good enough, critical information for actuation is a separate factor.

The development is reported of an ultra-rapid, point-of-care diagnostic device which harnesses surface acoustic wave (SAW) biochips, to detect HIV in a finger prick of blood within 10 seconds (samplein-result-out). The disposable quartz biochip, based on microelectronic components found in every consumer smartphone, is extremely fast because no complex labelling, amplification or wash steps are needed. A pocket-sized control box reads out the SAW signal and displays results electronically. High analytical sensitivity and specificity are found with model and real patient blood samples. The findings presented here open up the potential of consumer electronics to cut lengthy test waiting times, giving patients on the spot access to potentially life-saving treatment and supporting more timely public health interventions to prevent disease transmission.Ebola and Zika viruses offer a stark reminder that infectious diseases rank among the gravest threats to human health, and can spread rapidly and unpredictably. New infections will continue to emerge each year, and old enemies re-emerge, increasingly with acquired-drug resistance (e.g. gonorrhoea and HIV). Rapid diagnosis plays a crucial role in any outbreak situation, empowering patients to gain faster access to potentially life-saving treatment, and informing prevention strategies to protect the wider public. However, routine diagnostic tests based on enzyme linked immunosorbent assays (ELISAs) and polymerase chain reaction (PCR) are confined to centralized laboratories often requiring large, sophisticated, costly instrumentation and highly trained staff. Inherent delays occur between taking samples, conveying them to the laboratory, waiting for results to come back and subsequent follow up appointments 1-3 . This means that a patient often has to make multiple visits to a clinic in order to receive treatment, potentially over long distances. This delays prescribing of treatment with increased risk of suffering, mortality, and also incorrect prescription of antimicrobials.Recent policy drivers aim to widen access to testing using so called 'rapid' point-of-care tests (POCT) but the performance and implementation of these tests still remain a challenge 4 . The most common tests based on lateral flow technology are still relatively slow, requiring a 10-20 minute waiting time for results 5 . This exceeds a typical doctor's appointment (8-10 mins in the UK 6 ) necessitating changes to patient pathways within a clinic with additional on-costs and staffing implications. It is also notoriously difficult to interpret a faint lateral flow test line by eye, particularly for non-experts (e.g. self-testers) 1 . Those tests that are currently available are insensitive to recent (acute) infections 7 and lack the ability to automatically capture test results electronically, risking an incorrect reading, missed opportunities to link patients to care pathways and potential data loss for public health (e.g. during an Ebola outbreak) 8 . Alternatively, uneccesary treatment may be initi...