Concentric DNA Amplifier That Streamlines In-Solution Biorecognition and On-Particle Biocatalysis

Colloidal nanoparticle biosensors capable of on-particle biocatalysis are powerful tools for amplified detection of biomolecules. The development and practical uses of such concentric amplifiers can be complicated because of the on-particle biorecognition that involves varying interfacial factors at the biomolecule-nanoparticle interfaces. Herein, we reason that a nanoparticle biosensor equipped with an in-solution biorecognition element may be better fabricated, predicted, controlled, and performed. The in-solution biorecognition shall also be streamlined with the on-particle biocatalysis so that the overall analytical and kinetic performance is not compromised. As a testbed, we introduce a concentric DNA amplifier driven by an enzyme-powered three-dimensional DNA nanomachine, where a DNA walker can be instantly assembled onto a spherical nucleic acid (SNA) track through a polyadenosine anchor. As such, the free DNA walker can participate in reactions in a homogeneous solution before assembling to the SNA track. The instant and stable assembly enabled by both adsorption and complementary base pairing also ensures rapid on-particle biocatalysis. We demonstrate that the in-solution biorecognition effectively eliminates the binding hindrance encountered by the on-particle biorecognition and thus significantly reduced energy barriers for the detection of nucleic acids and proteins. Because of the in-solution biorecognition, our system can also be plugged readily into complex DNA strand displacement networks for rapid signal amplification.