The Monolith NT.LabelFree is a label-free and immobilization-free instrument capable of measuring biomolecular interactions using microscale thermophoresis (MST). MST measures the directed motion of molecules through a local temperature gradient, detecting a range of 10 nM to mM dissociation constants while consuming <4 µL of sample. The NT.LabelFree can monitor the binding of single ions (40 Da) or small molecules (300 Da) to a target as well as the binding of ribosomes (2.5 MDa). The NT.LabelFree can generate data in 10 minutes for medium-throughput purposes.