Scalable and High throughput Assembly of Layer-by-Layer Nanoparticles

Technology 

The technology operates by first loading nanoparticles and an oppositely charged polymer into separate inlets of a microfluidic mixing chip, where the two streams rapidly mix to deposit the first polymer layer onto the nanoparticle surface. The polymer is added at a carefully titrated polymer-to-nanoparticle weight ratio to achieve charge conversion of the nanoparticle surface while minimizing excess free polymer. After a 30-minute incubation to allow the polymer layer to adsorb, the coated nanoparticles are mixed with a second oppositely charged polymer in a second microfluidic stage to build the next layer. Because most of the polymer binds to the nanoparticles at the optimized ratio, intermediate purification steps are unnecessary, allowing continuous, high-throughput production of LbL nanoparticles.    

Problem Addressed 

A challenge of current LbL-NP synthesis is the serial nature of the layer deposition process, which often requires multiple purification steps and/or hard-to-scale mixing methods such as sonification, vortex mixing, centrifugation, and membrane-based approaches that risk unwanted NP-membrane interactions. Recent attempts to streamline LbL assembly, such as size exclusion and magnetic particle diversion, have been highly scale-dependent and impractical for NP production. Alternative approaches often require heating that can damage polymer structure and compromise nanoparticle integrity. The microfluidic mixing approach presented here overcomes these limitations by enabling continuous, scalable polymer deposition without requiring purification or thermal treatment.       

Advantages 

• Enables scalable, continuous polymer deposition that is compatible with cGMP conditions for clinical-grade NP production without the batch-processing limitations of traditional methods.  

• Eliminates the need for excess polymer and time-consuming purification steps by using titrated polymer-to-NP weight ratios, increasing LbL-NP throughput while avoiding the loss of NPs during purification.  

• Produces homogenous and stable nanoparticles with improved reproducibility compared with conventional tangential flow filtration-based methods, while maintaining equivalent in vivo therapeutic efficacy.   

• Supports multiple polymer chemistries and nanoparticle core types, providing flexibility for different therapeutic applications.