Real-time monitoring of single dendritic cell maturation using deep learning-assisted surface-enhanced Raman spectroscopy.

Dynamic real-time detection of dendritic cell (DC) maturation is pivotal for accurately predicting immune system activation, assessing vaccine efficacy, and determining the effectiveness of immunotherapy. The heterogeneity of cells underscores the significance of assessing the maturation status of each individual cell, while achieving real-time monitoring of DC maturation at the single-cell level poses significant challenges. Surface-enhanced Raman spectroscopy (SERS) holds great potential for providing specific fingerprinting information of DCs to detect biochemical alterations and evaluate their maturation status. We developed Au@CpG@PEG nanoparticle as a self-reporting nanovaccine for DC activation and maturation state assessment, utilizing a label-free SERS strategy. Fingerprint vibrational spectra of the biological components in different states of DCs were collected and analyzed using deep learning Convolutional Neural Networks (CNN) algorithms, aiding in the rapid and efficient identification of DC maturation. This approach enables dynamic real-time detection of DC maturation, maintaining accuracy levels above 98.92%. By employing molecular profiling, we revealed that the signal ratio of tryptophan-to-carbohydrate holds potential as a prospective marker for distinguishing the maturation status of DCs.