Future Prospects for Biomolecular Trapping with Nanostructured Metals

Abstract

Optical trapping with nanostructured metals has allowed for label-free tether-free analysis of single proteins (and other biomolecules) and their interactions with detector-limited time resolution and a duration extending to hours. This Perspective will provide a brief historical introduction, discuss recent advances to augment the technique with other approaches, and discuss the potential for improved performance and widescale adoption in a range of applications from biologics and drug discovery to fundamental biophysical studies.

Optical Monitoring of In Situ Iron Loading into Single, Native Ferritin Proteins

“…Pioneering techniques, such as interferometric scattering microscopy (iSCAT) 51 and nanopore electroosmotic trap (NEOtrap), 52 have demonstrated their potential in sizing proteins and monitoring protein dynamics but so far are limited to proteins larger than 50 kDa. 53 The DNH-based protein trapping allows the detection of small proteins down to 6.5 kDa. 45 Therefore, the technique presented in this work may be extended to monitoring the pore-gating dynamics of wide-range-sized proteins whose functions are dependent on their globular conformations.…”

Single Molecule Protein Segments Sequencing by a Plasmonic Nanopore

“…This phenomenon suggests that the laser in the SERS measurement may enhance the unfolding of the protein. We attribute such effect to the synergistic process between optical force and electric field force. , Optical force arises from the light field gradient around a target particle, which is the function of particle size, laser power and intensity gradient. , Here, the intensity gradient of light field can be significantly enlarged by the gold nanopore, − which pushes SM protein closer to gold surface and facilitate the chemical binding of protein on gold. The optical force-enhanced binding of protein on gold indeed provides additional force pointing to the opposite direction from electric field force.…”

“…The synergistic process-induced strong binding also explains the higher required potential in SERS detection than electrical detection to drive protein passing through the gold nanopore. Similar optical force-participated slow translocation is not rare. − , In some cases, the SM protein has been trapped for >100 s . The long stalling of cyt c inside a plasmonic nanopore is favorable for acquiring refined information on sequencing.…”

Electromagnetic Forces and Torques: From Dielectrophoresis to Optical Tweezers

“… 17 Furthermore, when working with apertures milled in a metallic substrate, this acts as a heat sink and greatly reduces the local temperature increase around the structures to only a few degrees Celsius . However, if needed, these substrates can also be properly engineered to act as efficient light-to-heat conversion systems. , In DEP experiments, while thermal effects generated by Joule and dielectric losses can significantly alter the local temperature around the metallic electrodesas well as in iDEP devicesthe temperature increase is usually reduced to only a few degrees Celsius when employing AC voltages with amplitudes smaller than 10 V. ,, …”