A new biosensor system may make it easier to monitor stem cells changing into mature cells like neurons, which could allow for a better understanding of diseases like Parkinson’s and support the development of new treatments.
The system was described in the paper, “Dual-Enhanced Raman Scattering-Based Characterization of Stem Cell Differentiation Using Graphene-Plasmonic Hybrid Nanoarray,” published in Nano Letters.
Stem cells are able to continuously divide and to differentiate into other types of cells. Because of these properties, stem cells have gained interest in a number of fields, including regenerative medicine for neurological conditions like Parkinson’s and Alzheimer’s. The basic idea is that they could be used to ‘replace’ brain cells (neurons, a type of nerve cell essential for cell-to-cell communication) that become damaged in the course of the disease.
However, applications like this would require exquisitely precise monitoring of these cells.
“A critical challenge is ensuring high sensitivity and accuracy in detecting biomarkers — indicators such as modified genes or proteins — within the complex stem cell microenvironment,” KiBum Lee, MS, PhD, a study co-author and professor at Rutgers University, said in a press release. “Our technology, which took four years to develop, has demonstrated great potential for analyzing a variety of interactions in stem cells.”
The new technology relies on a technique called Raman spectroscopy. In simple terms, this technique involves analyzing the way light scatters off of molecules, which — with the help of computational analyses — allows scientists to figure out details about the molecules being studied.
The signals generated by Raman spectroscopy are, by their very nature, tiny. In essence, the new system uses a combination of gold nanostructures and very thin layers of graphene to amplify these signals, a technique called surface-enhanced Raman scattering (SERS).
By analyzing what molecules a cell is making, particularly in terms of RNA, researchers can gain insight into what genes in a cell are ‘on’ or ‘off’ (gene expression), which is critical for understanding the development of stem cells.
Of note, gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.
As a proof-of-concept, the researchers analyzed neural stem cells, a specific subset of stem cells that, as their name suggests, can differentiate into neurons. They confirmed that their system showed that the pre-differentiation stem cells had high expression of the stem cell marker Nestin, whereas cells that differentiated into neurons had high expression of a neuron marker called TuJ1 (class III β-tubulin).
“Utilizing our developed system we can confirm approximately 2 orders of magnitude increase in Tuj1 RNA level [in differentiated cells],” the researchers wrote. Importantly, this finding was consistent with the results of analysis with polymerase chain reaction (PCR), which is a well-established technique for measuring RNA levels and, by extension, gene expression.
“Collectively,” the researchers concluded, “we believe that our graphene−Au [gold] hybrid SERS nanoarray system will not only be used for high-quality and high throughput bio/chemical molecule screening assays but will also help us to understand cellular phenomena such as disease progression and stem cell differentiation, thus leading to more effective therapies.”