A Very Large-Scale Microfluidic Integration (VLSMI) chip for producing lipid nanoparticles (LNPs) for RNA vaccines and therapeutics

Abstract Infini Fluidics is developing a Very Large-Scale Microfluidic Integration (VLSMI) chip for producing lipid nanoparticles (LNPs) for RNA therapeutics that can be scaled by a dynamic range of 1000x-from 100 mL/hr to 100 L/hr-thus enabling efficient and affordable use across all phases of drug development. LNPs are promising drug delivery vehicles that have been critical in the clinical translation of RNA therapeutics and vaccines, most notably the COVID-19 mRNA vaccines produced by Pfizer and Moderna. The COVID-19 pandemic has created unprecedented demand for rapid production of LNPs on a global scale, and this has highlighted some of the major limitations of current production methods. Indeed, a key challenge toward the broad clinical translation of LNP-based RNA therapeutics and vaccines is the development of formulation strategies that can robustly produce precisely defined formulations while accommodating scalable throughputs ranging from early development to clinical translation. To solve this problem, Infini Fluidics is developing the VLSMI chip, enabling scaling of production by 1000-fold while maintaining the potency typical of LNPs generated using microfluidics, thus enabling efficient and affordable production of high-quality LNPs across the phases of drug development. Infini's proposed VLSMI architecture integrates tens to hundreds of microfluidic mixing units onto a single, 4-inch silicon chip, just like transistors in a computer chip. The individual mixing units allow unprecedented control of LNP physiochemical and functional properties, while hundreds of these units allow flexible manufacturing of LNPs for clinical-phase trials or industrial-scale manufacturing. The specific aims of this Phase I project are 1: To evaluate the mixing efficiency of staggered herringbone mixing (SHM) design units at various lengths and flow rates using fluorescent images, Infini will evaluate four different device designs, implemented in silicon and glass, which is more compatible with the stringent requirements of pharmaceutical manufacturing. Mixing dynamics will be evaluated to identify the best performing SHM designs to synthesize LNPs, and 2: To evaluate LNP properties to determine the uniformity of the LNPs by encapsulating poly(C) as a model nucleic acid; here, Infini will evaluate LNP properties to demonstrate LNP production is predictable and accurate for commercial scale. Infini Fluidics' VLSMI chip solution will enable the fine control over LNP physiochemical and functional properties that is necessary for high LNP quality and potency and that has so far eluded macroscale LNP production methods. This technology can be widely applied to accelerate the development, evaluation, and distribution of RNA-based therapeutics and vaccines, helping to grow this burgeoning and promising field. This will enable success in new therapeutic areas and allow a timelier response to emerging pathogens.