Automated layer by layer construction of multilayer coated cores by TFF
Inventors
Boyd, James Gorham • Palath, Naveen • Cardenas, Edwin Jonathan
Assignees
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Publication Number
US-9975066-B2
Publication Date
2018-05-22
Expiration Date
Abstract
Layer by layer (“LBL”) construction of products by tangential flow filtration (TFF), or the like, is described, including computer controlled automation of such procedure for production of a multilayer coated core.
Core Innovation
The disclosed invention is an automated synthesis system for particles in which particles contain at least one polyelectrolyte layer deposited onto substrate cores. The system uses a tangential flow filtration component with a TFF loop and a permeate valve, and the permeate valve selectively performs permeation steps via control by a computer.
A closed-loop tubing network includes the TFF filter, a particle reservoir holding a suspension of the substrate cores, connecting means, and a product bag. The particle reservoir is in communication with a mechanical stirring means for maintaining dispersion of the substrate cores, and the system provides a circulatory loop that forms a continuous flow path for synthesis of the particles containing the at least one polyelectrolyte layer deposited onto the substrate cores.
The system further includes a soluble reagent addition manifold component in which delivery of a soluble reagent comprising the polyelectrolyte to the TFF component is controlled by at least one valve controlled by the computer. The closed loop tubing network extends to the soluble reagent addition manifold component and mounts to the at least one valve for dispensing a reagent to the TFF loop, and the circulatory loop provides synthesis in an aseptic manner.
Claims Coverage
Independent claim coverage centers on one principal inventive concept: a computer-controlled aseptic particle synthesis system using a closed-loop TFF loop with a permeate valve and a soluble reagent addition manifold for dispensing polyelectrolyte to deposit at least one polyelectrolyte layer onto substrate cores. Only one independent claim text is explicitly available in the provided content.
Computer-controlled closed-loop tangential flow filtration permeation for aseptic particle synthesis
A system comprising a computer, a TFF component having a TFF loop and a permeate valve configured to selectively perform permeation steps via control by the computer, and a closed-loop tubing network comprising the TFF filter, the particle reservoir, connecting means, and a product bag, wherein the system provides a circulatory loop that provides a continuous flow path for synthesis of particles containing at least one polyelectrolyte layer deposited onto the substrate cores in an aseptic manner.
Soluble polyelectrolyte reagent addition manifold controlled by computer valves
A soluble reagent addition manifold component wherein delivery of a soluble reagent comprising the polyelectrolyte to the tangential flow filtration component is controlled by at least one valve controlled by the computer, and wherein the closed loop tubing network extends to the soluble reagent addition manifold component and mounts to the at least one valve for dispensing a reagent to the tangential flow filtration loop.
The claims coverage is directed to an aseptic, computer-controlled particle synthesis system that combines a closed-loop TFF loop with permeation-step control and a computer-controlled soluble reagent addition manifold for dispensing polyelectrolytes to deposit polyelectrolyte layers onto substrate cores.
Stated Advantages
Improved deposition efficiency, reported as 100–250% higher PLL/PGA capture versus a manual method.
Documented Applications
Formation of microparticle vaccine constructs including polyelectrolyte layers, such as PLL/PGA homopolymers and a designed polypeptide DP, deposited onto substrate cores.
Use of layer-by-layer polyelectrolyte deposition with stepwise polarity and alternating zeta potential to demonstrate multilayer growth, including zeta potential measurements and amino-acid analysis.
Assessment of endotoxin for the disclosed microparticle constructs using endotoxin testing.
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