Single-Particle Counting Based on Digital Plasmonic Nanobubble Detection for Rapid and Ultrasensitive Diagnostics

Abstract

Rapid and sensitive diagnostics of infectious diseases is an urgent and unmet need as evidenced by the COVID-19 pandemic. Here we report a novel strategy, based on DIgitAl plasMONic nanobubble Detection (DIAMOND), to address these gaps. Plasmonic nanobubbles are transient vapor bubbles generated by laser heating of plasmonic nanoparticles, and allow single-particle detection. Using gold nanoparticles labels and an optofluidic setup, we demonstrate that DIAMOND achieves a compartment-free digital counting and works on homogeneous assays without separation and amplification steps. When applied to the respiratory syncytial virus diagnostics, DIAMOND is 150 times more sensitive than commercial lateral flow assays and completes measurements within 2 minutes. Our method opens new possibilities to develop single-particle digital detection methods and facilitate rapid and ultrasensitive diagnostics.

Nanoparticle Fragmentation below the Melting Point under Single Picosecond Laser Pulse Stimulation

“…30, 45, and 100 nm AuNPs were synthesized using the seed-growth method with 15 nm AuNPs as seeds. , Briefly, 15 nm AuNP (2.23 nM), HAuCl 4 (25 mM), and trisodium citrate (15 mM) solution were mixed and brought to the volume of 100 mL with Millipore water. Under rigorous mixing, hydroquinone (25 mM) solution was added into the vortex swiftly.…”

“…The solution was stirred for half an hour under high-speed stirring and then changed to low-speed stirring overnight. The volume of each solution is dependent on NP sizes and can be found in the previously published paper . Particles will be concentrated by centrifugation and stored in a 4 °C environment until the experiment.…”

“…The volume of each solution is dependent on NP sizes and can be found in the previously published paper. 42 Particles will be concentrated by centrifugation and stored in a 4 °C environment until the experiment. The centrifugation speed and time were dependent on particle sizes.…”

Nanoparticle fragmentation at solid state under single picosecond laser pulse stimulation

“…30, 45, 100 nm AuNPs were synthesized with the seed-growth method with 15 nm AuNPs as seeds [54][55] . Briefly, 15 nm AuNP (2.23 nM), HAuCl4 (25 mM) and trisodium citrate (15 mM) solution was mixed and brought to the volume of 100 mL with Millipore water.…”

“…The solution was stirred for half an hour under the high-speed stirring and then changed to low-speed stirring overnight. The volume of each solution is dependent on NP sizes and can be found in previously published paper 55 . Particles will be concentrated by centrifugation and stored in 4°C environment until experiment.…”