Continuous in-vitro physiological glucose sensing for co-cultured 3D tumour spheroids using SERS based nano particle sensors (SERS-gNPS)

Abstract

Evaluation of glucose in cancerous tumours acts as a hall mark for cancer progression and thus serves as a major interest in these days. Here, we have developed a biocompatible, surface enhanced Raman spectroscopy-based glucose Nano Particle Sensor (SERS-gNPS) to measure glucose dynamically in 3D Co-cultured Colon Cancer Tumour Spheroids (3D-CCTS). 3D-CCTS were produced using polydimethylsiloxane (PDMS) based µ-well array chip. SERS-gNPS was fabricated by conjugating 4-Mercaptophenylboronic acid (4-MPBA) to 50 nm silver nanoparticles (AgNP) and used under confocal Raman spectroscopy to measure glucose. The calibration curve shows direct relationship between Raman peak intensity at 1078 cm-1 with increasing glucose levels. The sensor has a limit of detection of 0.1 mM and found to be linear in the physiological range (1 mM – 10 mM) of glucose with an average standard deviation of ± 5%. SERS-gNPS was applied for continuous glucose measurement in an in-vitro 3D-CCTS and 3D Mono-cultured fibroblast Spheroids (3D-MS). The results revealed that the 3D-CCTS have more prominent glucose gradient (∼1 mM) as compared to 3D-MS (∼0.4 mM) from core to peripheral regions at 3 days to 5 days of culture. SERS-gNPS provides a platform for accurate and real-time measurement of glucose, and offers an enhanced understanding of glucose distribution in the tumour spheroids.