Gold Nanotapes and Nanopinecones in a Quantitative Lateral Flow Assay for the Cancer Biomarker Carcinoembryonic Antigen

Colorectal cancer is the third most common malignancy and the second leading cause of cancer death globally. Multiple studies have linked levels of carcinoembryonic antigen in patient serum to poor disease prognosis. Hence, the ability to detect low levels of carcinoembryonic antigen has applications in earlier disease diagnosis, assessment, and recurrence monitoring. Existing carcinoembryonic antigen detection methods often require multiple reagents, trained operators, or complex procedures. A method alleviating these issues is the lateral flow assay, a paper-based platform that allows the detection and quantification of target analytes in complex mixtures. The tests are rapid, are point-of-care, possess a long shelf life, and can be stored at ambient conditions, making them ideal for use in a range of settings. Although lateral flow assays typically use spherical gold nanoparticles to generate the classic red signal, recent literature has shown that alternate morphologies to spheres can improve the limit of detection. In this work, we report the application of alternative gold nanoparticle morphologies, gold nanotapes (∼35 nm in length) and gold nanopinecones (∼90 nm in diameter), in a lateral flow assay for carcinoembryonic antigen. In a comparative assay, gold nanopinecones exhibited a ∼2× improvement in the limit of detection compared to commercially available spherical gold nanoparticles for the same antibody loading and total gold content, whereas the number of gold nanopinecones in each test was ∼3.2× less. In the fully optimized test, a limit of detection of 14.4 pg/mL was obtained using the gold nanopinecones, representing a 24-fold improvement over the previously reported gold-nanoparticle-based carcinoembryonic antigen lateral flow assay.