Measurements of molecular size and shape on a chip

TL;DR

This paper introduces a high-throughput micro-chip imaging method that accurately measures molecular size, shape, and interactions in native conditions, enabling detailed analysis and diagnostics at very small scales.

Contribution

The authors present a novel micro-chip based approach for rapid, high-resolution measurement of molecular properties, including size, shape, and interactions, under native conditions.

Findings

Detects molecular weight differences across three orders of magnitude.

Quantifies molecular interactions over six orders of magnitude.

Senses insulin concentration in serum at sub-nanoliter scale.

Abstract

Size and shape are critical discriminators between molecular species and states. We describe a micro-chip based high-throughput imaging approach offering rapid and precise determination of molecular properties under native solution conditions. Our method detects differences in molecular weight across at least three orders of magnitude, and down to two carbon atoms in small molecules. We quantify the strength of molecular interactions over six orders of magnitude in affinity constant, and track reactions in real-time. Highly parallel measurements on individual molecules serve to characterize sample-state heterogeneity at the highest resolution, offering predictive input to model three-dimensional structure. We further leverage the method's structural sensitivity for diagnostics, exploiting ligand-induced conformational changes in the insulin receptor to sense insulin concentration in serum at the sub-nanoliter and sub-zeptomole scale.