The starting gold nanosphere seeds (left) are surrounded by a hollow, porous silver cage (middle) and then become a nanorattle filled with light-scattering dyes inside a gold outer shell (right). Image: Tuan Vo-Dinh, Duke University.
The starting gold nanosphere seeds (left) are surrounded by a hollow, porous silver cage (middle) and then become a nanorattle filled with light-scattering dyes inside a gold outer shell (right). Image: Tuan Vo-Dinh, Duke University.

Researchers at Duke University have developed a unique type of nanoparticle called a ‘nanorattle’ that can produce greatly enhanced light emission from within its outer shell.

Loaded with light-scattering dyes called Raman reporters, which are commonly used to detect biomarkers of disease in organic samples, this approach can amplify and detect signals from separate types of nanoprobes without needing an expensive machine or medical professional to read the results.

In a small proof-of-concept study, the nanorattles accurately identified head and neck cancers through an artificial intelligence (AI)-enabled point-of-care device that could revolutionize how these cancers and other diseases are detected in low-resource areas to improve global health. The researchers report their work in a paper in the Journal of Raman Spectroscopy.

“The concept of trapping Raman reporters in these so-called nanorattles has been done before, but most platforms had difficulty controlling the interior dimensions,” said Tuan Vo-Dinh, a distinguished professor of biomedical engineering at Duke.

“Our group has developed a new type of probe with a precisely tunable gap between the interior core and outer shell, which allows us to load multiple types of Raman reporters and amplify their emission of light called surface-enhanced Raman scattering,” Vo-Dinh said.

To make the nanorattles, the researchers start with a solid gold sphere about 20nm wide. After growing a layer of silver around the gold sphere to make a larger sphere (or cube), they use a corrosion process called galvanic replacement to hollow out the silver, creating a cage-like shell around the gold core. Next, they soak this structure in a solution containing positively charged Raman reporters, which are drawn into the outer cage by the negatively charged gold core. The outer hulls are then covered by an extremely thin layer of gold to lock the Raman reporters inside.

The result is a nanosphere (or nanocube) about 60nm wide with an architecture that resembles a rattle –a gold core trapped within an outer silver-gold shell. The gap between the core and shell is only about a few nanometers, just large enough to fit the Raman reporters. These tight tolerances are essential for controlling the Raman signal enhancement produced by the nanorattles.

When a laser shines on the nanorattles, it travels through the extremely thin outer shell and hits the Raman reporters within, causing them to emit light of their own. Because of how close the surfaces of the gold core and the outer gold/silver shell are together, the laser also excites groups of electrons, known as plasmons, on the metallic structures. These groups of electrons create an extremely powerful electromagnetic field due to the plasmons’ interaction with the metallic core-shell architecture, a process called plasmonic coupling, which amplifies the light emitted by the Raman reporters millions of times over.

“Once we had the nanorattles working, we wanted to make biosensing devices to detect infectious diseases or cancers before people even know they’re sick,” Vo-Dinh said. “With how powerful the signal enhancement of the nanorattles is, we thought we could make a simple test that could be easily read by anybody at the point-of-care.”

As a test of this approach, Vo-Dinh and his collaborators applied the nanorattle technology to a lab-on-a-stick device capable of detecting head and neck cancers, which appear anywhere between the shoulders and the brain, typically in the mouth, nose and throat. Survival rates for these cancers have hovered between 40% and 60% for decades. While those statistics have improved in recent years in the US, they have gotten worse in low-resource settings, where risk factors such as smoking, drinking and betel-nut chewing are much more prevalent.

“In low-resource settings, these cancers often present in advanced stages and result in poor outcomes due in part to limited examination equipment, lack of trained healthcare workers and essentially non-existent screening programs,” said Walter Lee, professor of head and neck surgery & communication sciences and radiation oncology at Duke, and a collaborator on the research.

“Having the ability to detect these cancers early should lead to earlier treatment and improvement in outcomes, both in survival and quality of life. This approach is exciting since it does not depend on a pathologist review and potentially could be used at the point of care.”

The prototype device uses specific genetic sequences that act like Velcro for the biomarkers the researchers are looking for – in this case, a specific mRNA that is overly abundant in people with head and neck cancers. When the mRNA in question is present, it acts like a tether that binds the nanorattles to magnetic beads. These beads are concentrated and held in place by an external magnet while everything else gets rinsed away. Researchers can then use a simple, inexpensive handheld device to look for light emitted by the nanorattles to see if any biomarkers were caught.

In the tests, the prototype device determined whether or not 20 samples came from patients that had head and neck cancer with 100% accuracy. These tests also showed that the nanorattle platform is capable of handling multiple types of nanoprobes, thanks to a machine-learning algorithm that can tease apart the separate signals, meaning they can target multiple biomarkers at once. This is the goal of the group’s current project funded by the US National Institutes of Health.

“Many mRNA biomarkers are overly abundant in multiple types of cancers, while other biomarkers can be used to evaluate patient risk and future treatment outcome,” Vo-Dinh said. “Detecting multiple biomarkers at once would help us differentiate between cancers, and also look for other prognostic markers such as Human Papillomavirus (HPV), and both positive and negative controls. Combining mRNA detection with novel nanorattle biosensing will result in a paradigm shift in achieving a diagnostic tool that could revolutionize how these cancers and other diseases are detected in low-resource areas.”

This story is adapted from material from Duke University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.