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Abstract Extraction of nucleic acids (NAs) is critical for many methods in molecular biology and bioanalytical chemistry. NA extraction has been extensively studied and optimized for a wide range of applications and its importance to society has significantly increased. The COVID-19 pandemic highlighted the importance of early and efficient NA testing, for which NA extraction is a critical analytical step prior to the detection by methods like polymerase chain reaction. This study explores simple, new approaches to extraction using engineered smart nanomaterials, namely NA-binding, intrinsically disordered proteins (IDPs), that undergo triggered liquid–liquid phase separation (LLPS). Two types of NA-binding IDPs are studied, both based on genetically engineered elastin-like polypeptides (ELPs), model IDPs that exhibit a lower critical solution temperature in water and can be designed to exhibit LLPS at desired temperatures in a variety of biological solutions. We show that ELP fusion proteins with natural NA-binding domains can be used to extract DNA and RNA from physiologically relevant solutions. We further show that LLPS of pH responsive ELPs that incorporate histidine in their sequences can be used for both binding, extraction and release of NAs from biological solutions, and can be used to detect SARS-CoV-2 RNA in samples from COVID-positive patients. 

Understanding and predicting the dynamics of complex fluid systems including liquid–liquid phase separation, relevant to both biological and engineered applications, typically uses a nonideal free energy. Introducing such a thermodynamic constraint into the Lattice-Boltzmann Method can be accomplished by altering either the equilibrium distribution function or the external force. The former requires a lengthy parameterization for a free energy of multiple independent variables which becomes cumbersome for more than three components. The latter has been done for a multicomponent compressible system, but a correction term for the force is required to recover the expected conservation equations. This work builds upon the incompressible single component forcing method from He et al. (Journal of Computational Physics, Vol. 152, No. 2, 1999) by deriving and implementing the required force needed to successfully recover the expected mass conservation from a nonideal free energy with an arbitrary number of components. This allows the simulation of more realistic phase separating fluid systems by including many interacting components, which is demonstrated here for up to five components and phases.