Abstract
This paper demonstrates the design, synthesis, simulation, and testing of three distinct geometries of plasmonic gold nanoparticles for on-chip DNA screening towards liquid biopsy. By employing a seed-mediated growth method, we have synthesized gold nanospheres, nanorods, and nanobipyramids. In parallel, we developed numerical simulations to understand the effects of nanoparticle geometry on the resonance features and refractive index sensitivity. Both experimental and simulation results were compared through a series of studies including in-solution and on-chip tests. We have thoroughly characterized the impact of nanoparticle geometry on the sensitivity to circulating tumor DNA, with immediate implications for liquid biopsy. The results agree well with theoretical predictions and simulations, including both bulk refractive index sensitivity and thin film sensitivity. Importantly, this work quantitatively establishes the link between nanoparticle geometry and efficacy in detecting rare circulating biomarkers. The nanobipyramids provided the highest sensitivity, approximately doubling the sensitivity compared to nanorods. To the best of our knowledge this is the first report carrying through geometric effects of simulation to clinically relevant biosensing. We put forth here synthesis and testing of three nanoparticle geometries, and a framework for both experimental and theoretical validation of plasmonic sensitivities towards liquid biopsy.
Highlights
This paper demonstrates the design, synthesis, simulation, and testing of three distinct geometries of plasmonic gold nanoparticles for on-chip DNA screening towards liquid biopsy
This paper thoroughly studies the effects of gold nanoparticle geometry on sensitivity towards Circulating tumor DNA (ctDNA) screening in liquid biopsy
The developed synthesis protocol resulted in relatively uniform particles with each of the desired geometries
Summary
This paper demonstrates the design, synthesis, simulation, and testing of three distinct geometries of plasmonic gold nanoparticles for on-chip DNA screening towards liquid biopsy. We developed numerical simulations to understand the effects of nanoparticle geometry on the resonance features and refractive index sensitivity Both experimental and simulation results were compared through a series of studies including in-solution and on-chip tests. The resonance is associated with highly sensitive electric fields which can measure changes in the local environment due to minute refractive index changes As such, this process does not require fluorescence or other readout methods to amplify signals[9] and can provide simpler sensing workflows with fewer chemical steps[10, 11]. This work is novel compared to the existing literature because of the thorough comparison of plasmonic simulation and experiment through to preclinical application This provides a framework for rational design of nanoparticles for biomarkerspecific plasmonic screening
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