The Experts below are selected from a list of 7842 Experts worldwide ranked by ideXlab platform
Paul G. Charette - One of the best experts on this subject based on the ideXlab platform.
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Surface acoustic waves (SAW) accelerated Microfluidic Mixing for improved microcalorimetry in biochips
The Journal of the Acoustical Society of America, 2012Co-Authors: Alan Renaudin, Vincent Aimez, Rémy Béland, Jean-pierre Cloarec, Yann Chevolot, Paul G. CharetteAbstract:By measuring very small local temperature changes, microcalorimetry is used to determine the rates of energy released or absorbed during biochemical reactions. The measurement signal-to-noise ratio can be significantly increased by accelerating the reaction kinetics by active Microfluidic Mixing. We present a biochip incorporating a self-referencing droplet-based microreactor consisting of a thermopile-based microcalorimeter (50 Ni/Au thermocouples in series) on a glass substrate with a surface acoustic wave (SAW)-based Microfluidic Mixing system on a LiNbO3 piezoelectric substrate. In our design, the SAW mechanical energy is transmitted from the piezoelectric substrate through the glass substrate to the droplets via a water film which acts as a pseudo mechanical impedance matching layer. The cumulative energy released by a standard calorimetric test reaction (sucrose dilution) is measured with the system. Results show that, by overcoming the diffusion-limited reaction rate, SAW-accelerated Mixing in the ...
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Accelerated surface plasmon resonance biosensing by surface acoustic waves microstreaming
2011 6th IEEE International Conference on Nano Micro Engineered and Molecular Systems, 2011Co-Authors: Alan Renaudin, Etienne Grondin, Vincent Chabot, Vincent Aimez, Paul G. CharetteAbstract:This paper describes our design incorporating surface plasmon resonance biosensing and surface acoustic wave active Microfluidic Mixing, integrated on a single LiNbO3 piezoelectric substrate. Validation experiments show that surface acoustic wave-induced microstreaming results in significant accelerated binding kinetics in a case of a standard avidin-biotin affinity assay.
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Integrated active Mixing and biosensing using surface acoustic waves (SAW) and surface plasmon resonance (SPR) on a common substrate
Lab on a Chip, 2010Co-Authors: Alan Renaudin, Etienne Grondin, Vincent Chabot, Vincent Aimez, Paul G. CharetteAbstract:This article presents a device incorporating surface plasmon resonance (SPR) sensing and surface acoustic wave (SAW) actuation integrated onto a common LiNbO(3) piezoelectric substrate. The device uses Rayleigh-type SAW to provide active Microfluidic Mixing in the fluid above the SPR sensor. Validation experiments show that SAW-induced Microfluidic Mixing results in accelerated binding kinetics of an avidin-biotin assay. Results also show that, though SAW action causes a parasitic SPR response due to heat injection into the fluid, a relatively brief relaxation time following the SAW pulses allows the effect to dissipate, without affecting the overall assay response. Since both SPR sensors and SAW transducers can be fabricated simultaneously using low-cost microfabrication methods on a single substrate, the proposed design is well-suited to lab-on-chip applications.
Alex K. K. Leung - One of the best experts on this subject based on the ideXlab platform.
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Microfluidic Mixing: A General Method for Encapsulating Macromolecules in Lipid Nanoparticle Systems
The journal of physical chemistry. B, 2015Co-Authors: Alex K. K. Leung, Yuen Yi C. Tam, Sam Chen, Ismail M. Hafez, Pieter R. CullisAbstract:Previous work has shown that lipid nanoparticles (LNP) composed of an ionizable cationic lipid, a poly(ethylene glycol) (PEG) lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and small interfering RNA (siRNA) can be efficiently manufactured employing Microfluidic Mixing techniques. Cryo-transmission electron microscopy (cryo-TEM) and molecular simulation studies indicate that these LNP systems exhibit a nanostructured core with periodic aqueous compartments containing siRNA. Here we examine first how the lipid composition influences the structural properties of LNP-siRNA systems produced by Microfluidic Mixing and, second, whether the Microfluidic Mixing technique can be extended to macromolecules larger than siRNA. It is shown that LNP-siRNA systems can exhibit progressively more bilayer structure as the proportion of bilayer DSPC lipid is increased, suggesting that the core of LNP-siRNA systems can exhibit a continuum of nanostructures depending on the proportions and structural preferences of component lipids. Second, it is shown that the Microfluidic Mixing technique can also be extended to encapsulation of much larger negatively charged polymers such mRNA (1.7 kb) or plasmid DNA (6 kb). Finally, as a demonstration of the generality of the Microfluidic Mixing encapsulation process, it is also demonstrated that negatively charged gold nanoparticles (5 nm diameter) can also be efficiently encapsulated in LNP containing cationic lipids. Interestingly, the nanostructure of these gold-containing LNP reveals a "currant bun" morphology as visualized by cryo-TEM. This structure is fully consistent with LNP-siRNA structure predicted by molecular modeling.
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Microfluidic Mixing: A General Method for Encapsulating Macromolecules in Lipid Nanoparticle Systems B
The Journal of Physical Chemistry, 2015Co-Authors: Alex K. K. Leung, Yuen Yi C. Tam, Sam Chen, Ismail M. Hafez, Pieter R. CullisAbstract:Previous work has shown that lipid nanoparticles (LNP) composed of an ionizable cationic lipid, a poly(ethylene glycol) (PEG) lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and small interfering RNA (siRNA) can be efficiently manufactured employing Microfluidic Mixing techniques. Cryo-transmission electron microscopy (cryo-TEM) and molecular simulation studies indicate that these LNP systems exhibit a nanostructured core with periodic aqueous compartments containing siRNA. Here we examine first how the lipid composition influences the structural properties of LNP–siRNA systems produced by Microfluidic Mixing and, second, whether the Microfluidic Mixing technique can be extended to macromolecules larger than siRNA. It is shown that LNP–siRNA systems can exhibit progressively more bilayer structure as the proportion of bilayer DSPC lipid is increased, suggesting that the core of LNP–siRNA systems can exhibit a continuum of nanostructures depending on the proportions and structural preferences of component lipids. Second, it is shown that the Microfluidic Mixing technique can also be extended to encapsulation of much larger negatively charged polymers such mRNA (1.7 kb) or plasmid DNA (6 kb). Finally, as a demonstration of the generality of the Microfluidic Mixing encapsulation process, it is also demonstrated that negatively charged gold nanoparticles (5 nm diameter) can also be efficiently encapsulated in LNP containing cationic lipids. Interestingly, the nanostructure of these gold-containing LNP reveals a “currant bun” morphology as visualized by cryo-TEM. This structure is fully consistent with LNP–siRNA structure predicted by molecular modeling.
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Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA
Molecular therapy. Nucleic acids, 2012Co-Authors: Nathan M Belliveau, Alex K. K. Leung, Jens Huft, Sam Chen, Paulo Jc Lin, Timothy Leaver, Andre Wild, Justin B. Lee, Robert Joseph Taylor, Ying K. TamAbstract:Lipid nanoparticles (LNP) are the leading systems for in vivo delivery of small interfering RNA (siRNA) for therapeutic applications. Formulation of LNP siRNA systems requires rapid Mixing of solutions containing cationic lipid with solutions containing siRNA. Current formulation procedures employ macroscopic Mixing processes to produce systems 70-nm diameter or larger that have variable siRNA encapsulation efficiency, homogeneity, and reproducibility. Here, we show that Microfluidic Mixing techniques, which permit millisecond Mixing at the nanoliter scale, can reproducibly generate limit size LNP siRNA systems 20 nm and larger with essentially complete encapsulation of siRNA over a wide range of conditions with polydispersity indexes as low as 0.02. Optimized LNP siRNA systems produced by Microfluidic Mixing achieved 50% target gene silencing in hepatocytes at a dose level of 10 µg/kg siRNA in mice. We anticipate that Microfluidic Mixing, a precisely controlled and readily scalable technique, will become the preferred method for formulation of LNP siRNA delivery systems.
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Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core.
Journal of Physical Chemistry C, 2012Co-Authors: Alex K. K. Leung, Ismail Hafez, Svetlana Baoukina, Igor V. Zhigaltsev, Elham Afshinmanesh, D. Peter Tieleman, Michael J. Hope, Carl L. Hansen, Nathan M Belliveau, PIETER RUTTER CULLISAbstract:Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading systems for enabling therapeutic applications of siRNA; however, the structure of these systems has not been defined. Here we examine the structure of LNP siRNA systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid, cholesterol and a polyethylene glycol (PEG) lipid formed using a rapid Microfluidic Mixing process. Techniques employed include cryo-transmission electron microscopy, 31P NMR, membrane fusion assays, density measurements, and molecular modeling. The experimental results indicate that these LNP siRNA systems have an interior lipid core containing siRNA duplexes complexed to cationic lipid and that the interior core also contains phospholipid and cholesterol. Consistent with experimental observations, molecular modeling calculations indicate that the interior of LNP siRNA systems exhibits a periodic structure of aqueous compartments, where some compartments contain siRNA. It is concluded that LNP s...
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Bottom-Up Design and Synthesis of Limit Size Lipid Nanoparticle Systems with Aqueous and Triglyceride Cores Using Millisecond Microfluidic Mixing
Langmuir, 2012Co-Authors: Igor V. Zhigaltsev, Alex K. K. Leung, Ismail Hafez, Jens Huft, Carl L. Hansen, Nathan M Belliveau, PIETER RUTTER CULLISAbstract:Limit size systems are defined as the smallest achievable aggregates compatible with the packing of the molecular constituents in a defined and energetically stable structure. Here we report the use of rapid Microfluidic Mixing for the controlled synthesis of two types of limit size lipid nanoparticle (LNP) systems, having either polar or nonpolar cores. Specifically, limit size LNP consisting of 1-palmitoyl, 2- oleoyl phosphatidylcholine (POPC), cholesterol and the triglyceride triolein were synthesized by Mixing a stream of ethanol containing dissolved lipid with an aqueous stream, employing a staggered herringbone micromixer. Millisecond Mixing of aqueous and ethanol streams at high flow rate ratios (FRR) was used to rapidly increase the polarity of the medium, driving bottom-up synthesis of limit size LNP systems by spontaneous assembly. For POPC/triolein systems the limit size structures consisted of a hydrophobic core of triolein surrounded by a monolayer of POPC where the diameter could be rationally engineered over the range 20−80 nm by varying the POPC/triolein ratio. In the case of POPC and POPC/cholesterol (55/45; mol/mol) the limit size systems achieved were bilayer vesicles of approximately 20 and 40 nm diameter, respectively. We further show that doxorubicin, a representative weak base drug, can be efficiently loaded and retained in limit size POPC LNP, establishing potential utility as drug delivery systems. To our knowledge this is the first report of stable triglyceride emulsions in the 20−50 nm size range, and the first time vesicular systems in the 20−50 nm size range have been generated by a scalable manufacturing method. These results establish Microfluidic Mixing as a powerful and general approach to access novel LNP systems, with both polar or nonpolar core structures, in the sub-100 nm size range.
David Sinton - One of the best experts on this subject based on the ideXlab platform.
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Circulating Optical Particle Trapping Through the Integration of Fiber Optics and Microfluidics
2007 Conference on Lasers and Electro-Optics (CLEO), 2007Co-Authors: J. T. Blakely, Reuven Gordon, David SintonAbstract:A dual-fiber optic trap is integrated with Microfluidics, and stable circulatory particle trapping is observed. The unique circulating and flow-dependant nature of the trap enables active Microfluidic Mixing as well as particle sorting and control.
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High-efficiency electrokinetic microMixing through symmetric sequential injection and expansion.
Lab on a chip, 2006Co-Authors: Jeffrey T Coleman, Jonathan Mckechnie, David SintonAbstract:Rapid electric field switching is an established Microfluidic Mixing strategy for electrokinetic flows. Many such Microfluidic mixers are variations on the T- or Y-form channel geometry. In these configurations, rapid switching of the electric field can greatly improve initial Mixing over that achieved with static-field Mixing. Due to a fundamental lack of symmetry, however, these strategies produce lingering cross-channel concentration gradients which delay complete Mixing of the fluid stream. In this paper, a field switching Microfluidic Mixing strategy which utilizes a symmetric sequential injection geometry with an expansion chamber to achieve high efficiency Microfluidic Mixing is demonstrated experimentally. A three-inlet injector sequentially interlaces two dissimilar incoming solutions. Downstream of the injector, the sequence enters an expansion chamber resulting in a dramatic (two orders of magnitude) decrease in Peclet number and rapid axial diffusive Mixing. The outlet concentration may be accurately varied over the full spectrum by tuning the duty cycle of the field switching waveform. The chips are designed with input from a previous numerical study, manufactured in poly(dimethylsiloxane) using soft-lithography based microfabrication, and tested using fluorescence microscopy. In the context of on-chip chemical processing for analytical operations, the demonstrated Mixing strategy has several features: high Mixing efficiency (99%), compact axial length (2.3 mm), steady outflow velocity, and readily variable outlet concentration (0.15 < c* < 0.95).
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a sequential injection Microfluidic Mixing strategy
Microfluidics and Nanofluidics, 2005Co-Authors: Jeffrey T Coleman, David SintonAbstract:A novel microMixing strategy is presented, which exploits the axial diffusion of a continuous sequence of discrete samples in a microchannel expansion. Mixing of a continuous sequence in an electroosmotic flow through a sudden expansion region is first modeled assuming an ideal, square-wave injection. The effect of expansion geometry and injection frequency is investigated. To facilitate sequential injection on-chip, two new sequential sample injection schemes are developed and coupled with an expansion region. The first of these designs produces two sample pairs that flow out of separate channels into a common expansion region. This design results in high axial Mixing rates but an inherent bias in the injector produces significant cross-stream concentration gradients in the output. These results indicate that the effectiveness of this microMixing strategy is critically dependant on the injection method. A second injector design effectively eliminates the effect of the injection bias using a symmetric microchannel configuration with three solution inlets. The resulting symmetrical injection micromixer produces a continuous uniform stream, 99% mixed, in only 2.3 mm.
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A Symmetry-Based Microfluidic Mixer for Rapid and Complete Mixing
ASME 3rd International Conference on Microchannels and Minichannels Part B cont’d, 2005Co-Authors: Jeffrey T Coleman, Jonathan Mckechnie, David SintonAbstract:Rapid electric field switching is an established Microfluidic Mixing strategy for electrokinetic flows. Many such Microfluidic mixers are variations on the t- or y-channel geometry. In these configurations, rapid switching of the electric field can greatly improve initial Mixing over that achieved with static-field Mixing. Due to a fundamental lack of symmetry, however, these strategies suffer from lingering cross-channel concentration gradients which delay complete Mixing of the fluid stream. Presented here is a field switching Microfluidic Mixing strategy which utilizes a symmetric sequential injector and an expansion chamber to achieve rapid and effectively complete Microfluidic Mixing. The three-inlet symmetric injector sequentially interlaces the two dissimilar incoming solutions. Just downstream of the injector, the sequence enters an expansion chamber and increased axial diffusion results in rapid Mixing. The completely mixed solution is refocused into the outlet stream. The Microfluidic chips are designed such that only the minimum number of independent fluid reservoirs is required. Chips are manufactured in polydimethylsiloxane using established soft-lithography based microfabrication methods. Fluorescence microscopy is employed to analyze, quantify and demonstrate the effectiveness of this Mixing strategy, and determine a preferred operating frequency range. The Microfluidic chip design is based on the findings of a recent numerical modelling based work that demonstrates the sequential injection microMixing concept.Copyright © 2005 by ASME
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Microfluidic Mixing Through Sequential Sample Injection With Rapid Expansion
Fluids Engineering, 2004Co-Authors: Jeffrey T Coleman, David SintonAbstract:A novel microMixing strategy is presented which exploits axial diffusion of a continuous sequence of discrete samples in a microchannel expansion. Mixing of a continuous sequence in an electroosmotic flow through a sudden expansion region is modelled first assuming an ideal, square-wave injection. Different expansion geometries are examined as well as different sample lengths in order to determine the potential effectiveness of the Mixing technique. To facilitate sequential injection on-chip, a new injection scheme is developed. The two outputs from the injector and an expansion region are integrated into a sequential injector micromixer chip design. Results for the sequential injection micromixer demonstrate rapid axial Mixing of the individual stream sequences. However, cross-stream gradients in the output channel develop due to an inherent bias in the injection technique. Microchannel configurations that mitigate this bias were presented.Copyright © 2004 by ASME
Nathan M Belliveau - One of the best experts on this subject based on the ideXlab platform.
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Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA
Molecular therapy. Nucleic acids, 2012Co-Authors: Nathan M Belliveau, Alex K. K. Leung, Jens Huft, Sam Chen, Paulo Jc Lin, Timothy Leaver, Andre Wild, Justin B. Lee, Robert Joseph Taylor, Ying K. TamAbstract:Lipid nanoparticles (LNP) are the leading systems for in vivo delivery of small interfering RNA (siRNA) for therapeutic applications. Formulation of LNP siRNA systems requires rapid Mixing of solutions containing cationic lipid with solutions containing siRNA. Current formulation procedures employ macroscopic Mixing processes to produce systems 70-nm diameter or larger that have variable siRNA encapsulation efficiency, homogeneity, and reproducibility. Here, we show that Microfluidic Mixing techniques, which permit millisecond Mixing at the nanoliter scale, can reproducibly generate limit size LNP siRNA systems 20 nm and larger with essentially complete encapsulation of siRNA over a wide range of conditions with polydispersity indexes as low as 0.02. Optimized LNP siRNA systems produced by Microfluidic Mixing achieved 50% target gene silencing in hepatocytes at a dose level of 10 µg/kg siRNA in mice. We anticipate that Microfluidic Mixing, a precisely controlled and readily scalable technique, will become the preferred method for formulation of LNP siRNA delivery systems.
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Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core.
Journal of Physical Chemistry C, 2012Co-Authors: Alex K. K. Leung, Ismail Hafez, Svetlana Baoukina, Igor V. Zhigaltsev, Elham Afshinmanesh, D. Peter Tieleman, Michael J. Hope, Carl L. Hansen, Nathan M Belliveau, PIETER RUTTER CULLISAbstract:Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading systems for enabling therapeutic applications of siRNA; however, the structure of these systems has not been defined. Here we examine the structure of LNP siRNA systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid, cholesterol and a polyethylene glycol (PEG) lipid formed using a rapid Microfluidic Mixing process. Techniques employed include cryo-transmission electron microscopy, 31P NMR, membrane fusion assays, density measurements, and molecular modeling. The experimental results indicate that these LNP siRNA systems have an interior lipid core containing siRNA duplexes complexed to cationic lipid and that the interior core also contains phospholipid and cholesterol. Consistent with experimental observations, molecular modeling calculations indicate that the interior of LNP siRNA systems exhibits a periodic structure of aqueous compartments, where some compartments contain siRNA. It is concluded that LNP s...
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Bottom-Up Design and Synthesis of Limit Size Lipid Nanoparticle Systems with Aqueous and Triglyceride Cores Using Millisecond Microfluidic Mixing
Langmuir, 2012Co-Authors: Igor V. Zhigaltsev, Alex K. K. Leung, Ismail Hafez, Jens Huft, Carl L. Hansen, Nathan M Belliveau, PIETER RUTTER CULLISAbstract:Limit size systems are defined as the smallest achievable aggregates compatible with the packing of the molecular constituents in a defined and energetically stable structure. Here we report the use of rapid Microfluidic Mixing for the controlled synthesis of two types of limit size lipid nanoparticle (LNP) systems, having either polar or nonpolar cores. Specifically, limit size LNP consisting of 1-palmitoyl, 2- oleoyl phosphatidylcholine (POPC), cholesterol and the triglyceride triolein were synthesized by Mixing a stream of ethanol containing dissolved lipid with an aqueous stream, employing a staggered herringbone micromixer. Millisecond Mixing of aqueous and ethanol streams at high flow rate ratios (FRR) was used to rapidly increase the polarity of the medium, driving bottom-up synthesis of limit size LNP systems by spontaneous assembly. For POPC/triolein systems the limit size structures consisted of a hydrophobic core of triolein surrounded by a monolayer of POPC where the diameter could be rationally engineered over the range 20−80 nm by varying the POPC/triolein ratio. In the case of POPC and POPC/cholesterol (55/45; mol/mol) the limit size systems achieved were bilayer vesicles of approximately 20 and 40 nm diameter, respectively. We further show that doxorubicin, a representative weak base drug, can be efficiently loaded and retained in limit size POPC LNP, establishing potential utility as drug delivery systems. To our knowledge this is the first report of stable triglyceride emulsions in the 20−50 nm size range, and the first time vesicular systems in the 20−50 nm size range have been generated by a scalable manufacturing method. These results establish Microfluidic Mixing as a powerful and general approach to access novel LNP systems, with both polar or nonpolar core structures, in the sub-100 nm size range.
PIETER RUTTER CULLIS - One of the best experts on this subject based on the ideXlab platform.
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Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core.
Journal of Physical Chemistry C, 2012Co-Authors: Alex K. K. Leung, Ismail Hafez, Svetlana Baoukina, Igor V. Zhigaltsev, Elham Afshinmanesh, D. Peter Tieleman, Michael J. Hope, Carl L. Hansen, Nathan M Belliveau, PIETER RUTTER CULLISAbstract:Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading systems for enabling therapeutic applications of siRNA; however, the structure of these systems has not been defined. Here we examine the structure of LNP siRNA systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid, cholesterol and a polyethylene glycol (PEG) lipid formed using a rapid Microfluidic Mixing process. Techniques employed include cryo-transmission electron microscopy, 31P NMR, membrane fusion assays, density measurements, and molecular modeling. The experimental results indicate that these LNP siRNA systems have an interior lipid core containing siRNA duplexes complexed to cationic lipid and that the interior core also contains phospholipid and cholesterol. Consistent with experimental observations, molecular modeling calculations indicate that the interior of LNP siRNA systems exhibits a periodic structure of aqueous compartments, where some compartments contain siRNA. It is concluded that LNP s...
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Bottom-Up Design and Synthesis of Limit Size Lipid Nanoparticle Systems with Aqueous and Triglyceride Cores Using Millisecond Microfluidic Mixing
Langmuir, 2012Co-Authors: Igor V. Zhigaltsev, Alex K. K. Leung, Ismail Hafez, Jens Huft, Carl L. Hansen, Nathan M Belliveau, PIETER RUTTER CULLISAbstract:Limit size systems are defined as the smallest achievable aggregates compatible with the packing of the molecular constituents in a defined and energetically stable structure. Here we report the use of rapid Microfluidic Mixing for the controlled synthesis of two types of limit size lipid nanoparticle (LNP) systems, having either polar or nonpolar cores. Specifically, limit size LNP consisting of 1-palmitoyl, 2- oleoyl phosphatidylcholine (POPC), cholesterol and the triglyceride triolein were synthesized by Mixing a stream of ethanol containing dissolved lipid with an aqueous stream, employing a staggered herringbone micromixer. Millisecond Mixing of aqueous and ethanol streams at high flow rate ratios (FRR) was used to rapidly increase the polarity of the medium, driving bottom-up synthesis of limit size LNP systems by spontaneous assembly. For POPC/triolein systems the limit size structures consisted of a hydrophobic core of triolein surrounded by a monolayer of POPC where the diameter could be rationally engineered over the range 20−80 nm by varying the POPC/triolein ratio. In the case of POPC and POPC/cholesterol (55/45; mol/mol) the limit size systems achieved were bilayer vesicles of approximately 20 and 40 nm diameter, respectively. We further show that doxorubicin, a representative weak base drug, can be efficiently loaded and retained in limit size POPC LNP, establishing potential utility as drug delivery systems. To our knowledge this is the first report of stable triglyceride emulsions in the 20−50 nm size range, and the first time vesicular systems in the 20−50 nm size range have been generated by a scalable manufacturing method. These results establish Microfluidic Mixing as a powerful and general approach to access novel LNP systems, with both polar or nonpolar core structures, in the sub-100 nm size range.