Diagnosing brain cancer without a biopsy
Early diagnosis of primary central nervous system lymphoma (PCNSL) remains challenging because brain biopsies are invasive and imaging often lacks molecular specificity. A team led by researchers at Shenzhen University has now developed a minimally invasive fibre-optic plasmonic sensor capable of detecting PCNSL-associated microRNAs in the eye’s aqueous humor with attomolar sensitivity.
At the heart of the approach is a black phosphorus (BP)–engineered surface plasmon resonance (SPR) interface. An ultrathin BP layer is deposited on a gold-coated fiber tip. Because of the work-function difference between BP and gold, electrons transfer from BP into the Au film, creating a strongly enhanced local electric field at the metal–semiconductor interface. This BP–Au charge-transfer nano-interface amplifies refractive-index changes at the surface far more efficiently than conventional metal-only SPR chips, enabling the detection of molecular interactions that would otherwise be too subtle to resolve and pushing the limit of detection down to 21 attomolar without nucleic-acid amplification. The BP layer also provides a high-area, biocompatible surface for immobilizing RNA reporters.
To achieve sequence specificity, the researchers integrated CRISPR-Cas13a, an RNA-guided nuclease that becomes catalytically active only when its target sequence is perfectly matched to a designed CRISPR RNA (crRNA). When the target microRNA (miR-21) is present, activated Cas13a cleaves RNA reporters attached to the BP-modified fiber surface, releasing gold nanoparticles and reducing the local refractive index. The resulting optical shift is read out in real time through the SPR response of the BP-enhanced fiber probe, providing single-nucleotide-resolved detection directly on the plasmonic interface.
With this combined strategy, the sensor achieved a limit of detection of 21 attomolar in buffer and successfully distinguished single-base-mismatched microRNAs. In tests on aqueous-humor samples from patients with PCNSL, the CRISPR-BP-FOSPR assay produced results that closely matched clinical qPCR data, despite operating without any amplification steps.
Because aqueous-humor aspiration is a minimally invasive ophthalmic procedure, this BP-driven plasmonic platform may offer a practical route for early PCNSL screening, longitudinal monitoring, and potentially the diagnosis of other neurological diseases reflected in eye-fluid biomarkers. More broadly, the work showcases how black-phosphorus-based charge-transfer interfaces can be used to engineer next-generation, fibre-integrated biosensors that combine extreme sensitivity with molecular precision.
Read the full article
Yanqi Ge et al 2025 Rep. Prog. Phys. 88 070502
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