Scientists have developed a compact Raman imaging system that can reliably tell cancerous tissue apart from normal tissue. The approach could support earlier cancer detection and help move advanced molecular imaging tools beyond research laboratories and into more practical clinical settings.
The imaging system is designed to detect extremely weak signals from surface-enhanced Raman scattering (SERS) nanoparticles that are engineered to attach to tumor markers. Once these nanoparticles are applied to a sample or to the area being examined, the system reads their Raman signal and automatically highlights regions that are more likely to contain tumor tissue.
“Traditional methods for cancer-related diagnosis are time-consuming and labor-intensive because they require staining tissue samples and having a pathologist look for any abnormalities,” said research team leader Zhen Qiu from the Institute for Quantitative Health Science and Engineering (IQ), Michigan State University. “While our system would not immediately replace pathology, it could serve as a rapid screening tool to accelerate diagnosis.”
Published results show major gains in sensitivity
In Optica, Optica Publishing Group’s journal for high-impact research, Qiu and colleagues report that their system can distinguish cancerous cells from healthy ones while detecting Raman signals that are about four times weaker than those measured by a comparable commercial system. This improved sensitivity comes from combining a swept-source laser — which changes wavelength during analysis — with an ultra-sensitive detector called a superconducting nanowire single-photon detector (SNSPD).
“This technology could eventually enable portable or intraoperative devices that enable clinicians to detect cancers at earlier stages, improve the accuracy of biopsy sampling and monitor disease progression through less invasive testing,” said Qiu. “Ultimately, such advances could enhance patient outcomes and reduce diagnostic delays, accelerating the path from detection to treatment.”
Pushing detection limits with superconducting detectors
Qiu’s lab studies how SNSPDs can be used to enhance a range of imaging technologies. SNSPDs rely on a superconducting wire that can detect individual particles of light, allowing the system to capture extremely weak optical signals at high speed while keeping background noise very low.
For this project, the researchers aimed to build a platform that could measure Raman signals far fainter than those detected by existing Raman systems. Raman imaging works by mapping a sample’s chemical composition through the unique light-scattering fingerprints of its molecules. These signals can be strengthened by using SERS nanoparticles.
“Combining this advanced detector with a swept-source Raman architecture that replaces a bulky camera and collects light more efficiently resulted in a system with a detection limit well beyond that of comparable commercial systems,” said Qiu. “Also, the fiber coupling configuration and compact design facilitate system miniaturization and future clinical translation.”
Strong tumor contrast across multiple sample types
To test the system, the team used SERS nanoparticles coated with hyaluronan acid, which enables the particles to bind to CD44, a surface protein found on many tumor cells. Initial experiments with simple nanoparticle solutions showed that the system could reach femtomolar sensitivity. The researchers then applied the imaging platform to cultured breast cancer cells, mouse tumors, and healthy tissue samples.
“The SERS signals were strongly concentrated in tumor samples, with only minimal background detected in healthy tissue,” said Qiu. “This demonstrates both the system’s exceptional sensitivity and its ability to provide reliable tumor-versus-healthy contrast. Moreover, by adjusting or substituting the targeting molecule, this method could be adapted for other cancer types.”
Next steps toward clinical use
According to the researchers, additional work is needed before the system can be used in clinical settings. Future improvements will focus on increasing readout speed and expanding validation studies. The team is exploring faster laser sources, including VCSELs, and testing whether narrowing the sweep range can further improve performance. They also plan multiplexing experiments that use different nanoparticles to target multiple biomarkers at the same time.
The researchers acknowledge industry collaborator Quantum Opus, which provided the SNSPD devices used in this work.
