Consensus ranking of protein affinity to identify point mutations has not been established. Therefore, analytical techniques that can detect subtle variations without interfering with native biomolecular interactions are required. Here we report a rapid method to identify point mutations by a single nanoparticle sensing system. DNA-directed gold crystallization forms rod-like nanoparticles with bridges based on structural design. The nanoparticles enhance Rayleigh light scattering, achieving high refractive-index sensitivity, and enable the system to monitor even a small number of protein-DNA binding events without interference. Analysis of the binding affinity can compile an atlas to distinguish the potential of various point mutations recognized by MutS protein. We use the atlas to analyze the presence and type of single point mutations in BRCA1 from samples of human breast and ovarian cancer cell lines. The strategy of synthesis-by-design of plasmonic nanoparticles for sensors enables direct identification of subtle biomolecular binding distortions and genetic alterations.

Precise control over the structure of metal nanomaterials is important for developing advanced nanobiotechnology. Assembly methods of nanoparticles into structured blocks have been widely demonstrated recently. However, synthesis of nanocrystals with controlled, three-dimensional structures remains challenging. Here we show a directed crystallization of gold by a single DNA molecular regulator in a sequence-independent manner and its applications in three-dimensional topological controls of crystalline nanostructures. We anchor DNA onto gold nanoseed with various alignments to form gold nanocrystals with defined topologies. Some topologies are asymmetric including pushpin-, star- and biconcave disk-like structures, as well as more complex jellyfish- and flower-like structures. The approach of employing DNA enables the solution-based synthesis of nanocrystals with controlled, three-dimensional structures in a desired direction, and expands the current tools available for designing and synthesizing feature-rich nanomaterials for future translational biotechnology.

This work discusses prominent advantages and advances in single-nanoparticle characterization and synthesis, and gives an outlook on particle-based biomedical diagnosis.

Various thrombotic disorders have been treated with the anticoagulant warfarin. However, a small change in warfarin concentration may lead to drug adverse reactions or therapeutic failure due to its narrow therapeutic index. Therefore, the dose of warfarin must be monitored for each patient during therapy in real-time and in a sensitive and stable manner. In this work, we designed a magnetoelastic (ME) biosensor using Metglas alloy 2826 to detect VKORC1 genotypes, which is one of the most important known genetic determinants of warfarin dosing. The sensor enabled both fast responses to DNA binding and wireless transmission of signals. Specifically in the target recognition layer, the sensor introduced an avidin–biotin interaction system for signal amplification by increasing the surface load mass. The resonance frequency shift of the signal was linear to the concentration of the target in the range of 0.1 fM to 10 pM, with a detection limit (LOD) of 0.00389 fM (S/N = 3) and a sensitivity of 45.7 Hz pM⁻¹. Importantly, this ME-based biosensor was small and portable without the use of any optical labels, which has high potential to be applied in advanced biomedical diagnosis of nucleic acids and proteins.