Endoscopic surgery, a primary treatment option for patients with solid cancers, risks the recurrence of cancer if any cancerous cells are missed during the tumor removal process. To address this issue, surgeons have started using fluorescence-guided surgery (FGS), where a fluorescent probe, preferentially binding to tumor cells, is injected into patients. This aids in the easy identification of lesions using specialized endoscopes that emit the necessary excitation light. However, due to the high heterogeneity of tumors, a single fluorescent probe might not suffice for all detections, leading to a push towards multi-tracer FGS that uses multiple fluorescent probes to detect a broader range of tumors and reduce false positives and negatives. Yet, most clinically approved endoscopes are designed for a single tracer, and multi-tracer devices in development tend to be bulky due to their need for numerous imaging sensors and optical components.

In a new study, a research team from University of Illinois Urbana–Champaign (Champaign, IL, USA) has developed a novel endoscopic imaging system aimed at accelerating the adoption of multi-tracer FGS. Central to this innovation is a unique hexa-chromatic bioinspired imaging sensor (BIS), inspired by the visual system of the mantis shrimp. It comprises three layers of vertically stacked photodetectors covered with a checkerboard-like arrangement of filters for visible light and near-infrared (NIR) light. The single-chip camera created can capture light across six different spectral channels, enabling the detection of subtle differences in fluorescence emission from the imaged tissue. This BIS can distinguish between fluorescent tracers with emission peaks just 20 nanometers (nm) apart, a capability not available in current clinically approved imaging instruments.

To leverage the BIS effectively, the researchers developed a suitable excitation light source for activating the fluorescent tracers, using custom bifurcated optical fibers connected to three independent light sources—a white LED and two NIR lasers at 665 and 785 nm. The fibers' combined output was coupled at the start of the rigid endoscope, reducing the device's bulkiness compared to other multi-tracer imaging systems by using a single imaging sensor and a single light input. Following characterization and benchmarking tests to ascertain the device's spatial resolution and sensitivity, in vivo experiments were performed on a mouse model for breast cancer, injecting a 680-nm tracer, an 800-nm tracer, or a mixture of both. The proposed system effectively differentiated between the fluorescence signatures produced by each tracer and their mixtures.

In order to demonstrate their endoscope's clinical potential, the researchers used it to image lung cancer nodules freshly removed from patients. Even though the patients had been injected with just one fluorescent tracer, the device accurately distinguished malignant nodules from healthy tissue. This research marks a significant engineering advancement that could enable the wider use of multi-tracer FGS, helping doctors identify smaller or hidden tumors due to its higher spatial resolution and ability to detect minor variations in fluorescence emission. This could potentially improve long-term survival for patients with operable cancer.

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