Layer-by-Layer Nanoparticle Assembly for Biomedicine: Mechanisms, Technologies, and Advancement via Acoustofluidics

The deposition of thin films plays a crucial role in surface engineering, tailoring structural modifications, and functionalization across diverse applications. Layer-by-layer self-assembly, a prominent thin-film deposition method, has witnessed substantial growth since its mid-20th-century inception, driven by the discovery of eligible materials and innovative assembly technologies. Of these materials, micro- and nanoscopic substrates have received far less interest than their macroscopic counterparts; however, this is changing. The catalogue of eligible materials, including nanoparticles, quantum dots, polymers, proteins, cells and liposomes, along with some well-established layer-by-layer technologies, have combined to unlock impactful applications in biomedicine, as well as other areas like food fortification, and water remediation. To access these fields, several well-established technologies have been used, including tangential flow filtration, fluidized bed, atomization, electrophoretic assembly, and dielectrophoresis. Despite the invention of these technologies, the field of particle layer-by-layer still requires further technological development to achieve a high-yield, automatable, and industrially ready process, a requirement for the diverse, reactionary field of biomedicine and high-throughput pharmaceutical industry. This review provides a background on layer-by-layer, focusing on how its constituent building blocks and bonding mechanisms enable unmatched versatility. The discussion then extends to established and recent technologies employed for coating micro- and nanoscopic matter, evaluating their drawbacks and advantages, and highlighting promising areas in microfluidic approaches, where one distinctly auspicious technology emerges, acoustofluidics. The review also explores the potential and demonstrated application of acoustofluidics in layer-by-layer technology, as well as analyzing existing acoustofluidic technologies beyond LbL coating in areas such as cell trapping, cell sorting, and multidimensional particle manipulation. Finally, the review concludes with future perspectives on layer-by-layer nanoparticle coating and the potential impact of integrating acoustofluidic methods.