Sophisticated biomolecular nanoparticles, either of biological origin or from tailored biomolecular components, enable various tasks such as targeted molecule delivery or enhanced enzymatic function. It cannot be neglected, however, that these nanoparticles frequently exhibit high heterogeneity in terms of composition, size, and reactivity, necessitating single-particle measurement. Here, we measure nanoscale and molecular properties of single nanoparticles via anti-Brownian electrokinetic (ABEL) trapping. In this scheme, a suspended nanoparticle’s location is detected label-free via interferometric scattering, and electrokinetic feedback is applied to counteract the particle’s Brownian motion and keep it observable for seconds-minutes. By trapping individual particles, we can acquire readouts on the particle’s size while fluorescent markers spectroscopically report on biochemical properties. Residual Brownian fluctuations enable precise estimations of single-particle hydrodynamic radius. We demonstrate these capabilities with carboxysomes, fascinating bacterial nanocompartments responsible for carbon fixation. The unique combination of trapping with spectroscopic readouts enables investigation into nanoscopic biomolecular characteristics with unprecedented detail.
William Benjamin Carpenter (Sun,) studied this question.