Methods and apparatuses to non-destructively and periodically sample a small quantity of intracellular proteins and mRNA from the same single cell or cells for an extended period of time. Specifically, describe herein are non-perturbative methods for time-resolved, longitudinal extraction and quantitative measurement of intracellular proteins and nucleic acids from a variety of cell types using systems including nanostraws.

A method for predicting the metabolic state of a cell culture of cells of a specific cell type includes providing a metabolic model of a cell of the specific cell type, and performing at each of a plurality of points in time during cultivation of the cell culture, receiving measured concentrations of a plurality of extracellular metabolites and a measured cell density in the culture medium; inputting the received measurements as input parameter values to a trained machine learning program logic-MLP; predicting extracellular fluxes of the extracellular metabolites at a future point in time by the MLP; performing metabolic flux analysis to calculate the intracellular fluxes at the future point in time based on the predicted extracellular fluxes and the stoichiometric equations of the metabolic model.