Capture Assisted by Buoyancy: Monte Carlo Simulation of Protein Separation

Buoyant silica microbubbles have recently been developed and commercialized for capturing and separating cells and pro-teins. The buoyancy motion both separates the analyte and accelerates analyte capture. Additionally, they can be coupled with magnetic microspheres for ultrasensitive buoyant-analyte-magnetic (BAM) sandwich immunoassays. This report uses Monte Carlo simulations of buoyant microsphere motion and Brownian diffusion to investigate how buoyancy affects the capture rate of analytes and subsequent BAM-complex formation. To computationally simulate buoyant capture kinetics, nucleocapsid proteins (the analyte) are first seeded with a 3D matrix of buoyant particles underneath. At every computational step, each nucleocapsid protein and buoyant microbubble moves by simulated diffusion, and the microbubbles also rise by buoyant force. When a protein comes within a microbubble’s radius, it can be “captured” (with a given probability) and thereafter moves with the microbubble. These simulations show that buoyant motion enhances protein capture rate, and for constant total microbubble volume, a larger radius accelerates capture. These findings will help for optimizing experimental protocols and interpreting results for buoyant capture and BAM complex formation.