Getting More Lateral Flow Test Sensitivity with Nanoshell Probes

Silica-gold nanoshells highlight how good probe design can boost assay performance.

The Scientist Creative Services Team and nanoComposix
Jan 19, 2022

Nanoparticles are emerging as powerful tools for research, therapeutic, and diagnostic applications. In particular, their utility as lateral flow test probes has gained prominence amid the COVID-19 pandemic. Here, scientists must have a thorough understanding of nanoparticle properties and the factors that modulate them to generate probes with high diagnostic sensitivity.

Nanoparticles can be created using many different materials, including noble metals such as gold and silver, natural and synthetic polymers, and biological components such as lipids. Gold is especially popular due to its stability, which not only limits aggregation, but also allows gold nanoparticles (AuNPs) to be prepared in various shapes and structures, including spheres, rods, and shells. This chemical and physical stability also results in excellent biocompatibility, making AuNPs well suited for biomedical applications.1

Given this, it is unsurprising that AuNPs are widely used as lateral flow test probes. Proper probe selection is imperative for the performance of any lateral flow test assay, and AuNPs come in a variety of shapes, sizes, and conformations, including nanorods, nanocubes, and nanospheres. The current industry standard is the 40 nm gold nanosphere, which offers a surface area suitable for targeting analytes across a wide range of sizes, as well as excellent color contrast for visual readouts.2 However, nanospheres may not provide enough sensitivity for diagnostic applications such as COVID-19 testing where early detection is paramount.

One way to improve sensitivity is to enhance the visual contrast generated by each nanoparticle bound with the analyte of interest. To accomplish this, scientists at nanoComposix have developed nanoshells comprised of a 110-120 nm silica core and a 12-18 nm gold shell.2,3 This particular conformation yields a high-contrast blue-grey2,3 or blue-green4 color that can be visualized with as little as 500,000 binding events compared to 5,000,000 with 40 nm nanospheres.3 The silica core also has a much lower mass than gold, which improves settling time and flow rates compared to solid gold spheres of equivalent size.2,3

Researchers have already investigated the potential of nanoComposix nanoshells for a number of real-world diagnostic applications. Lateral flow test assays for detecting the SARS-CoV-2 nucleocapsid protein were more sensitive when nanoshell probes were used, compared to nanospheres or latex probes. Nanoshell probes delivered robust signal intensity even at protein concentrations below 5 ng/ml, something that the other probes could not match. They also required the least amount of antibody conjugate per strip.4 Similarly, nanoshell probes proved 10-fold more sensitive than nanosphere probes in a lateral flow test for the key cardiac biomarker troponin I.3

Finally, a research team from Cornell University recently used nanoshells to develop a lateral flow test for point-of-care prostate-specific antigen (PSA) rapid screening.2 They found that nanoshells provided a five-fold lower detection limit compared to 40 nm gold nanospheres, without the need for any signal amplification, resulting in a detection range of 0.5-150 ng/mL without sacrificing accuracy.2

Gold nanoparticles from nanoComposix, including nanospheres and nanoshells, represent solutions for scientists’ needs, whether for research, therapeutic, or diagnostic applications. The continued development of AuNP probes for lateral flow tests will aid the future development of even more sensitive diagnostics for COVID-19 and other diseases.


  1. X. Hu et al., “Multifunctional gold nanoparticles: a novel nanomaterial for various medical applications and biological activities,” Front Bioeng Biotechnol, 8:990, 2020.
  2. B. Srinivasan et al., “Highly portable quantitative screening test for prostate-specific antigen at point of care,” Curr Res Biotech, 3:288-99, 2021.
  3. S.J. Oldenburg, “Increasing the sensitivity of lateral flow diagnostic assays with ultra-bright nanoparticle reporters [Application note],” nanoComposix, 2019.
  4. “Performance comparison of commonly used nanoparticle probes in SARS-CoV-2 nucleocapsid protein LFA [Application note],” nanoComposix, 2021.