Uncovering metabolic gradients evolution using 3D-printed multiwell plates tailored to Raman spectroscopy

Solid tumors are complex microenvironments where uneven distributions of nutrients, oxygen, and waste critically affect cancer progression and therapy resistance. Rapid tumor cell proliferation and poor vascularization create heterogeneity that current in vitro methods struggle to replicate and monitor dynamically. To address this, we developed a 3D-printed cell culture platform that models nutrient and metabolite gradients with precision while enabling real-time monitoring using Raman spectroscopy integrated with multivariate analysis. This system tracks key metabolic changes such as glucose consumption, lactate release, and pH shifts directly in the medium, ensuring non-invasive and continuous assessment. By simulating diverse tumor niches, our platform advances tumor microenvironment modeling, supports precision medicine, and facilitates personalized therapeutic strategies, paving the way for improved clinical outcomes and laboratory automation.