Integrated SERS-Microfluidic Sensor Based on Nano-Micro Hierarchical Cactus-like Array Substrates for the Early Diagnosis of Prostate Cancer

Abstract

The detection and analysis of cancer cell exosomes with high sensitivity and precision are pivotal for the early diagnosis and treatment strategies of prostate cancer. To this end, a microfluidic chip, equipped with a cactus-like array substrate (CAS) based on surface-enhanced Raman spectroscopy (SERS) was designed and fabricated for the detection of exosome concentrations in Lymph Node Carcinoma of the Prostate (LNCaP). Double layers of polystyrene (PS) microspheres were self-assembled onto a polyethylene terephthalate (PET) film to form an ordered cactus-like nanoarray for detection and analysis. By combining EpCAM aptamer-labeled SERS nanoprobes and a CD63 aptamer-labeled CAS, a ‘sandwich’ structure was formed and applied to the microfluidic chips, further enhancing the Raman scattering signal of Raman reporter molecules. The results indicate that the integrated microfluidic sensor exhibits a good linear response within the detection concentration range of 105 particles μL−1 to 1 particle μL−1. The detection limit of exosomes in cancer cells can reach 1 particle μL−1. Therefore, we believed that the CAS integrated microfluidic sensor offers a superior solution for the early diagnosis and therapeutic intervention of prostate cancer.