Early diagnosis and metastasis monitoring for pancreatic cancer are extremely difficult due to a lack of sensitive liquid biopsy methods and reliable biomarkers. Herein, we developed easy-to-prepare and effective polydopamine-modified immunocapture substrates and an ultrathin polydopamine-encapsulated antibody-reporter-Ag(shell)–Au(core) multilayer (PEARL) Surface-Enhanced Raman Scattering (SERS) nano-tag with a quantitative signal of the Raman reporter at 1072 cm⁻¹, which achieved ultrasensitive and specific detection of pancreatic cancer-derived exosomes with a detection limit of only one exosome in 2 μL of sample solution (approximately 9 × 10⁻¹⁹ mol L⁻¹). Furthermore, by analyzing a 2 μL clinical serum sample, the migration inhibitory factor (MIF) antibody-based SERS immunoassay could not only discriminate pancreatic cancer patients (n = 71) from healthy individuals (n = 32), but also distinguish metastasized tumors from metastasis-free tumors, and Tumor Node Metastasis (TNM) P1–2 stages from the P3 stage (the discriminatory sensitivity was 95.7%). Thus, this novel immunoassay provides a powerful tool for the early diagnosis, classification and metastasis monitoring of pancreatic cancer patients.

A facile hydrothermal method was used to synthesize luminescent carbon dots from single-walled carbon nanotubes (SWNTs). Then 4,7,10-trioxa-1,13-tridecanediamine (TTDDA) was grafted onto the carbon dots to increase their water solubility and luminescent properties. The as-prepared carbon dots were characterized by UV-Vis absorption, infrared (IR), Raman, fluorescence, and transmission electron microscopy (TEM). The results confirmed that these carbon dots were monodispersed in water and emitted bright yellow fluorescence. The surface modified carbon dots were used to label biological cells, and the images obtained by a laser scanning confocal microscope showed that the carbon dots were gradually taken up by HeLa cells. The cytotoxicity of such carbon dots toward HeLa cells was very low, for 24 h the LC₅₀ was over 5 mg mL⁻¹.

Recent advances in biointerfaces have led to the development of wearable devices that can provide insights into personal health. As wearable modules, microneedles can extract analytes of interest from interstitial fluid in a minimally invasive fashion. However, some microneedles are limited by their ability to perform highly effective extraction and real-time monitoring for macromolecule biomarkers simultaneously. Here we show the synergetic effect of CRISPR-activated graphene biointerfaces, and report an on-line wearable microneedle patch for extraction and in vivo long-term monitoring of universal cell-free DNA. In this study, this wearable system enables real-time monitoring of Epstein-Barr virus, sepsis, and kidney transplantation cell-free DNA, with anti-interference ability of 60% fetal bovine serum, and has satisfactory stable sensitivity for 10 days in vivo. The experimental results of immunodeficient mouse models shows the feasibility and practicability of this proposed method. This wearable patch holds great promise for long-term in vivo monitoring of cell-free DNA and could potentially be used for early disease screening and prognosis.