Rational Design of Semiconducting Oligomer for Third Harmonic Generation Bioimaging of Ultradeep Brain Imaging with NIR‐IIb Excitation

Abstract

AbstractMultiphoton microscopy (MPM) has unparalleled promise in high‐spatiotemporal bioimaging within the tissue‐transparent window of 1500 to 1700 nm, commonly referred to as the near‐infrared‐IIb (NIR‐IIb) region. However, so far, surprisingly few cases of non‐fluorescent MPM probes have been reported, and their imaging performances are relatively limited. Herein, this study introduces a highly efficient third harmonic generation (THG) probe based on semiconducting oligomer derivatives (BTICs), which exhibit strong THG responses under NIR‐IIb (1700 nm) excitation. Leveraging halogen chemistry, semiconducting oligomers with varying halogen substitutions and nanoparticles (NPs) exhibit unexpectedly high THG performance across different aggregation states upon NIR‐IIb excitation. The BTICs NPs exhibit a large THG conversion efficiency (1215 × 10−84 cm6 s2 photon−2) and exceptional resistance to photobleaching. Furthermore, the biocompatibility and in vivo THG angiography capabilities of BTICs NPs are validated, achieving the visualisation of deep‐brain vasculature with unprecedented spatial resolution at a record‐high imaging depth of 1745 µm. The pioneering exploitation of semiconducting oligomer‐based THG probes establishes a new class of high‐performance materials, enabling ultra‐deep THG imaging of the brain and advancing the design of next‐generation THG imaging platforms.