RNA vaccines and other nucleic‑acid therapeutics are typically packaged inside lipid nanoparticles (LNPs). MIT researchers have devised a method that produces these particles much faster, with precise control over size and shape, and can run automatically without human intervention.
Conventional LNP production mixes an ethanol‑solubilized lipid stream with an acidic mRNA solution at a 1:3 flow‑rate ratio. This imbalance promotes encapsulation but offers no fine control of particle geometry. In a previous study published in ACS Nano, the MIT team introduced a two‑step mixing scheme: first, mRNA and lipids are combined at equal flow rates; then, after a short delay, a buffer is added to halt further growth. Longer residence times yield larger particles, while the buffer concentration in the second step determines shape, enabling a transition from spherical to avocado‑like elongated particles.
The new ACS Nano paper automates this two‑step process. A commercially available dynamic light scattering (DLS) instrument continuously measures particle size as they form. The system accepts a target size, adjusts the delay time and buffer composition in real time, and, if the measured size deviates, closes the loop to correct the parameters.
The project showcases MIT’s Undergraduate Research Opportunities Program (UROP). Undergraduate students in applied mathematics, computer science, and chemical engineering collaborated to integrate advanced software engineering with chemical process hardware. Data collected from rapid parameter sweeps were used to train a machine‑learning model that predicts which combination of factors will generate a desired size or shape, dramatically reducing experimental trial‑and‑error.
Particle size is critical because it dictates biodistribution. An LNP designed at 150 nm behaves very differently in the body compared to one at 70 nm, even when all other components are identical. The technology has been patented and is being commercialized through a spin‑out called BIZON Labs, with support from MIT’s delta v accelerator, the U.S. FDA, and the National Cancer Institute.
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