We demonstrate the first, to our knowledge, delivery of megawatt peak power, single-mode mid-infrared (MIR) femtosecond pulses at 5–6 μm using a silica-based anti-resonant hollow core fiber (AR-HCF). Benefiting from the light confinement inside the hollow core, the AR-HCF exhibits high damage thresholds, reliable power stability, efficient spatial beam self-cleaning, and pulse shape preservation. Pumped by a homemade LGS-based two-stage optical parametric amplifier generating high-power ∼200 fs pulses, the fiber achieves a maximum delivered peak power of 4 MW at 5.1 μm and 5 MW at 6.1 μm, with peak intensities reaching 100 GW/cm², despite fiber losses exceeding 2 dB/m. This flexible, meter-scale delivery system demonstrates exceptional potential for addressing the challenges of high peak power MIR laser delivery in precise, minimally invasive interventional ablation, particularly at resonant peaks such as amide-I (6.1 μm) and cholesterol esters (5.75 μm).

The selective laser ablation of pancreatic ductal adenocarcinoma (PDAC), which is an aggressive and highly lethal solid tumor, is of great significance. However, existing thermal ablation methods such as radiofrequency, microwave, and laser ablation all lack the ability to selectively ablate cancerous tissue while preserving healthy pancreas. In this study, by developing a 6.1 µm femtosecond laser at the resonant wavelength of collagen with an output power exceeding 1 W, we demonstrate selective ablation of PDACs from 13 patients with significant preservation of normal pancreatic tissue, based on the collagen-enriched nature of PDACs. Two to three times higher ablation efficiency in PDACs than in normal pancreatic tissues is demonstrated. Through resonant laser ablation, the growth rate of cultured PDACs is suppressed to 1/8 of that observed in the control group. Moreover, hollow-core fiber is designed and developed to guide the 6.1 µm femtosecond laser for minimally invasive ablation, which further validates the translational potential. The developed selective laser ablation technique could be extended to other collagen-rich malignant tumors—such as melanomas, breast tumors, colon tumors, kidney tumors, and gliomas, making it a versatile medical technology.

Mid-infrared (MIR) femtosecond lasers, resonant with the absorption bands of amide-related molecular groups in the range of 6.1 to 6.5 μm, have been demonstrated to be effective for tissue ablation. However, the flexible and stable delivery of such pulses to micrometer-scale tissue regions for controlled ablation remains challenging. Here, we utilize a silica-based anti-resonant hollow-core fiber (AR-HCF) to deliver high-power MIR femtosecond pulses with high temporal and spectral fidelity, featuring pulse durations of approximately 340 fs and peak power densities exceeding 1 GW/cm², for selective tissue ablation. Benefiting from the small numerical aperture of the AR-HCF, a relatively stable and consistent beam spot size can be maintained over a millimeter-scale propagation distance. Precise control of the ablation depth can be achieved by appropriately selecting the scanning parameters, with penetration depths reaching the sub-millimeter scale. Furthermore, for the first time, we systematically compare the tissue ablation performance of MIR femtosecond lasers at resonant wavelengths (6.4 and 6.1 μm) and a non-resonant wavelength (5.5 μm) under identical scanning conditions. An ablation depth ratio of more than 8:1 is observed, demonstrating the high efficiency and selectivity of the resonance-based ablation mechanism. These results establish flexible delivery of high-power MIR femtosecond pulses in tissue-resonant bands via silica-based AR-HCF as a powerful platform for selective, precise, and efficient tissue ablation, providing a promising approach for interventional and minimally invasive surgery.