Controlled vesicle self-assembly in continuous two phase flow microfluidic channels
Inventors
Jahn, Andreas • Vreeland, Wyatt N. • Locascio, Laurie E. • Gaitan, Michael
Assignees
National Institute of Standards and Technology NIST
Publication Number
US-9198645-B2
Publication Date
2015-12-01
Expiration Date
2024-07-21
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Abstract
Methods for the formation of liposomes that encapsulate reagents in a continuous 2-phase flow microfluidic network with precision control of size, for example, from 100 nm to 300 nm, by manipulation of liquid flow rates are described. By creating a solvent-aqueous interfacial region in a microfluidic format that is homogenous and controllable on the length scale of a liposome, fine control of liposome size and polydispersity can be achieved.
Core Innovation
The invention describes methods for the formation of liposomes that encapsulate reagents in a continuous two-phase flow microfluidic network, enabling precise control of liposome size, for example, from 100 nm to 300 nm, by manipulation of liquid flow rates. This is achieved by creating a solvent-aqueous interfacial region in a microfluidic format that is homogenous and controllable on the length scale of a liposome. Such control results in fine control of liposome size and polydispersity.
The problem addressed is that traditional liposome preparation methods rely on mixing bulk phases, resulting in inhomogeneous chemical and mechanical conditions during formation and producing liposomes that are often polydisperse in size and lamellarity. Bulk production methods cause significant chemical fluctuations and mechanical perturbations, leading to inhomogeneous nanoparticle populations.
The invention leverages the characteristics of microfluidic systems, including dominant interfacial forces, negligible inertial forces, enhanced heat and diffusional mass transfer, and laminar flow conditions to create well-defined and predictable interfacial regions between fluids. This allows control over chemical and mechanical conditions on the length scale equivalent to a liposome, enabling the formation of liposomes in constant, homogeneous conditions, thereby producing populations more uniform in size and of low polydispersity.
Claims Coverage
The patent encompasses two independent claims featuring inventive methods and apparatus for controlled liposome formation using microfluidic flow systems. The main inventive features are outlined below.
Method for producing liposome-containing compositions by microfluidic hydrodynamic focusing
Providing a solvent stream of lipids or lipid-forming materials dissolved in a water-miscible solvent through a central microchannel of 100 μm or less hydrodynamic diameter; impinging at least one aqueous stream through side microchannels to hydrodynamically focus the solvent stream, establishing, under laminar flow, an interfacial region within the central microchannel where solvent and aqueous streams diffuse into each other to create conditions for liposomes to self-assemble with mean diameter from 100 nm to 300 nm and size distribution of 20% or less.
Encapsulation of reagents within liposomes during microfluidic formation
Including a reagent in either the lipid/lipid-forming material composition or the aqueous composition (or both), whereby at least a portion of the reagent is encapsulated within the liposomes formed in the microfluidic process.
These inventive features collectively provide precise, controlled production of liposomes with defined size and low polydispersity, leveraging microfluidic laminar flows for hydrodynamic focusing and controlled self-assembly, including reagent encapsulation.
Stated Advantages
Fine control of liposome size and homogeneity through manipulation of flow conditions in microfluidic channels.
Production of monodisperse liposome populations with low polydispersity without requiring subsequent processing steps.
Controlled encapsulation of reagents within liposomes during formation.
Ability to mimic biological systems by controlling chemical and mechanical conditions on the length scale of liposomes.
Potential for scale-up using multiplexed multichannel microfluidic systems for on-demand drug encapsulation and delivery.
Documented Applications
Use of liposome-containing compositions for targeted drug delivery and DNA transfection.
On-demand drug encapsulation and delivery applications.
Potential adaptation for synthesis and self-assembly of nanoscale particles for other applications in nanotechnology.
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