Recent advancements in single-cell metabolic analysis for pharmacological research

Cellular heterogeneity is crucial for understanding tissue biology and disease pathophysiology.Pharmacological research is being advanced by single-cell metabolic analysis,which offers a technique to identify variations in RNA,proteins,metabolites,and drug molecules in cells.In this review,the recent advancement of single-cell metabolic analysis techniques and their applications in drug metabolism and drug response are summarized.High-precision and controlled single-cell isolation and manipulation are provided by microfluidics-based methods,such as droplet microfluidics,microchamber,open microfluidic probe,and digital microfluidics.They are used in tandem with variety of detection techniques,including optical imaging,Raman spectroscopy,electrochemical detection,RNA sequencing,and mass spectrometry,to evaluate single-cell metabolic changes in response to drug administration.The advantages and disadvantages of different techniques are discussed along with the challenges and future directions for single-cell analysis.These techniques are employed in pharmaceutical analysis for studying drug response and resistance pathway,therapeutic targets discovery,and in vitro disease model evaluation.