Labelfree

Labelfree refers to analytical and detection approaches that measure biomolecular interactions and properties without attaching externally detectable labels such as fluorescent dyes, isotopic tags, or enzyme reporters. In label-free methods, information is obtained from intrinsic molecular properties or from direct measurement of binding events, enabling observation of interactions in near-native conditions.

Common label-free techniques include surface plasmon resonance (SPR), quartz crystal microbalance with dissipation monitoring (QCM-D), biolayer interferometry (BLI), and various interferometric and ellipsometric methods that detect changes in mass, refractive index, or impedance upon binding. In label-free proteomics, mass spectrometry-based approaches quantify proteins by comparing signal intensities without isotopic or chemical labels. Label-free imaging and sensing also use optics or acoustics to produce contrast from intrinsic properties such as refractive index or mechanical stiffness. Some methods monitor cells or tissues without labels, using phase contrast, holography, or optical coherence tomography.

Applications of labelfree technologies span drug discovery and development, biomarker validation, clinical diagnostics, environmental testing, and fundamental biophysics. Label-free readouts are valued for real-time monitoring, reduced sample preparation, and the ability to study native interactions and kinetics.

Advantages include avoiding perturbation from labels, preserving native activity, and enabling kinetic measurements. Limitations include lower sensitivity for certain targets, potential non-specific binding, higher instrument cost, and more complex data analysis. Proper controls and calibration are essential for reliable interpretation.

History and status: Label-free approaches matured from biosensor technologies in the late 20th century and have become mainstream in research and industry, with ongoing advances in sensitivity, multiplexing, and data interpretation.