date: 2019-03-09T07:54:24Z
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pdf:docinfo:title: A Microfluidic Split-Flow Technology for Product Characterization in Continuous Low-Volume Nanoparticle Synthesis
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subject: A key aspect of microfluidic processes is their ability to perform chemical reactions in small volumes under continuous flow. However, a continuous process requires stable reagent flow over a prolonged period. This can be challenging in microfluidic systems, as bubbles or particles easily block or alter the flow. Online analysis of the product stream can alleviate this problem by providing a feedback signal. When this signal exceeds a pre-defined range, the process can be re-adjusted or interrupted to prevent contamination. Here we demonstrate the feasibility of this concept by implementing a microfluidic detector downstream of a segmented-flow system for the synthesis of lipid nanoparticles. To match the flow rate through the detector to the measurement bandwidth independent of the synthesis requirements, a small stream is sidelined from the original product stream and routed through a measuring channel with 2  2 m cross-section. The small size of the measuring channel prevents the entry of air plugs, which are inherent to our segmented flow synthesis device. Nanoparticles passing through the small channel were detected and characterized by quantitative fluorescence measurements. With this setup, we were able to count single nanoparticles. This way, we were able to detect changes in the particle synthesis affecting the size, concentration, or velocity of the particles in suspension. We envision that the flow-splitting scheme demonstrated here can be transferred to detection methods other than fluorescence for continuous monitoring and feedback control of microfluidic nanoparticle synthesis.
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dc:title: A Microfluidic Split-Flow Technology for Product Characterization in Continuous Low-Volume Nanoparticle Synthesis
modified: 2019-03-09T07:54:24Z
cp:subject: A key aspect of microfluidic processes is their ability to perform chemical reactions in small volumes under continuous flow. However, a continuous process requires stable reagent flow over a prolonged period. This can be challenging in microfluidic systems, as bubbles or particles easily block or alter the flow. Online analysis of the product stream can alleviate this problem by providing a feedback signal. When this signal exceeds a pre-defined range, the process can be re-adjusted or interrupted to prevent contamination. Here we demonstrate the feasibility of this concept by implementing a microfluidic detector downstream of a segmented-flow system for the synthesis of lipid nanoparticles. To match the flow rate through the detector to the measurement bandwidth independent of the synthesis requirements, a small stream is sidelined from the original product stream and routed through a measuring channel with 2  2 m cross-section. The small size of the measuring channel prevents the entry of air plugs, which are inherent to our segmented flow synthesis device. Nanoparticles passing through the small channel were detected and characterized by quantitative fluorescence measurements. With this setup, we were able to count single nanoparticles. This way, we were able to detect changes in the particle synthesis affecting the size, concentration, or velocity of the particles in suspension. We envision that the flow-splitting scheme demonstrated here can be transferred to detection methods other than fluorescence for continuous monitoring and feedback control of microfluidic nanoparticle synthesis.
pdf:docinfo:subject: A key aspect of microfluidic processes is their ability to perform chemical reactions in small volumes under continuous flow. However, a continuous process requires stable reagent flow over a prolonged period. This can be challenging in microfluidic systems, as bubbles or particles easily block or alter the flow. Online analysis of the product stream can alleviate this problem by providing a feedback signal. When this signal exceeds a pre-defined range, the process can be re-adjusted or interrupted to prevent contamination. Here we demonstrate the feasibility of this concept by implementing a microfluidic detector downstream of a segmented-flow system for the synthesis of lipid nanoparticles. To match the flow rate through the detector to the measurement bandwidth independent of the synthesis requirements, a small stream is sidelined from the original product stream and routed through a measuring channel with 2  2 m cross-section. The small size of the measuring channel prevents the entry of air plugs, which are inherent to our segmented flow synthesis device. Nanoparticles passing through the small channel were detected and characterized by quantitative fluorescence measurements. With this setup, we were able to count single nanoparticles. This way, we were able to detect changes in the particle synthesis affecting the size, concentration, or velocity of the particles in suspension. We envision that the flow-splitting scheme demonstrated here can be transferred to detection methods other than fluorescence for continuous monitoring and feedback control of microfluidic nanoparticle synthesis.
pdf:docinfo:creator: Holger Bolze, Peer Erfle, Juliane Riewe, Heike Bunjes, Andreas Dietzel and Thomas P. Burg
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Creation-Date: 2019-03-09T07:54:24Z
Author: Holger Bolze, Peer Erfle, Juliane Riewe, Heike Bunjes, Andreas Dietzel and Thomas P. Burg
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Keywords: lipid nanoparticles; online analysis; microfluidics; plug flow mixer; fluorescence; precipitation; single particle analysis; nanoparticle characterization
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dc:creator: Holger Bolze, Peer Erfle, Juliane Riewe, Heike Bunjes, Andreas Dietzel and Thomas P. Burg
dcterms:created: 2019-03-09T07:54:24Z
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dcterms:modified: 2019-03-09T07:54:24Z
title: A Microfluidic Split-Flow Technology for Product Characterization in Continuous Low-Volume Nanoparticle Synthesis
Last-Save-Date: 2019-03-09T07:54:24Z
pdf:docinfo:keywords: lipid nanoparticles; online analysis; microfluidics; plug flow mixer; fluorescence; precipitation; single particle analysis; nanoparticle characterization
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creator: Holger Bolze, Peer Erfle, Juliane Riewe, Heike Bunjes, Andreas Dietzel and Thomas P. Burg
dc:subject: lipid nanoparticles; online analysis; microfluidics; plug flow mixer; fluorescence; precipitation; single particle analysis; nanoparticle characterization
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