A NIR-IIb-excited capsule endoscope enabling high-contrast fluorescence imaging via spectrally-isolated detection for early-stage gastrointestinal cancer

Early detection of gastrointestinal cancers faces significant challenges, mainly including the invasiveness of wired endoscopes, the limited tissue penetration depth of white light capsule endoscopy (CE), and the low signal-to-noise ratio (SNR) and contrast caused by excitation light interference in traditional fluorescence imaging CE. Herein, we developed a near-infrared-IIb (NIR-IIb) window-excited fluorescence imaging capsule endoscope (FICE) for the high-contrast diagnosis of early-stage gastrointestinal cancers. The FICE employs a 1550-nm central wavelength NIR-IIb laser diode to precisely shape the excitation beam for selective activation of upconversion nanoprobes (UCNPs) aggregates in lesion tissues, stimulating them to emit 540 nm green fluorescence-the most sensitive wavelength for CMOS imaging chips. Utilizing 1550 nm excitation light facilitates enhanced penetration into biological tissues and the detection method with an excitation-emission spectral separation of more than 1000 nm effectively eliminates background interference, thereby yielding diagnostic images with ultrahigh SNR and superior contrast. Proof-of-concept experiments in nude mice demonstrated that this FICE achieved specific fluorescence detection of subcutaneous and colonic mucosal tumors with a penetration depth of up to 6 mm and fluorescence-to-background contrast ratios exceeding 90%. Ex vivo validation in porcine tissues confirmed the FICE's imaging capability within realistic anatomical environments. Furthermore, we designed a wireless power supply and posture control system to provide continuous energy and precise motion control for the FICE. To our knowledge, this paper presents the first NIR-IIb-excited FICE, offering a non-invasive, high-contrast and high-SNR diagnostic tool for early gastrointestinal cancer detection and demonstrating remarkable clinical potential.