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Updated: Apr 4, 2026

A Robust Method for the Large-Scale Production of Spheroids for High-Content Screening and Analysis Applications
Published on: December 28, 2021
Hierarchical assembly may be a way to make large information-rich structures
1Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA. swhitelam@lbl.gov.
Abstract:
Self-assembly in the laboratory can now yield 'information-rich' nanostructures in which each component is of a distinct type and has a defined spatial position. Ensuring the thermodynamic stability of such structures requires inter-component interaction energies to increase logarithmically with structure size, in order to counter the entropy gained upon mixing component types in solution. However, self-assembly in the presence of strong interactions results in general in kinetic trapping, so suggesting a limit to the size of an (equilibrium) structure that can be self-assembled from distinguishable components. Here we study numerically a two-dimensional hierarchical assembly scheme already considered in experiment. We show that this scheme is immune to the kinetic traps associated with strong 'native' interactions (interactions designed to stabilize the intended structure), and so, in principle, offers a way to make large information-rich structures. In this scheme the size of an assembled structure scales exponentially with the stage of assembly, and assembly can continue as long as random motion is able to bring structures into contact. The resulting superstructure could provide a template for building in the third dimension. The chief drawback of this scheme is that it is particularly susceptible to kinetic traps that result from 'non-native' interactions (interactions not required to stabilize the intended structure); the scale on which such a scheme can be realized therefore depends upon how effectively this latter kind of interaction can be suppressed.
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