Nano Today
Volume 11, Issue 6, December 2016, Pages 778-792
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Review
Microfluidic hydrodynamic focusing for synthesis of nanomaterials

https://doi.org/10.1016/j.nantod.2016.10.006Get rights and content

Highlights

  • An overview of recent progress in microfluidic hydrodynamic focusing is presented.

  • Distinct designs of flow focusing methods and mechanisms are discussed.

  • A future perspective on the key applications and research directions is given.

Abstract

Microfluidics expands the synthetic space such as heat transfer, mass transport, and reagent consumption to conditions not easily achievable in conventional batch processes. Hydrodynamic focusing in particular enables the generation and study of complex engineered nanostructures and new materials systems. In this review, we present an overview of recent progress in the synthesis of nanostructures and microfibers using microfluidic hydrodynamic focusing techniques. Emphasis is placed on distinct designs of flow focusing methods and their associated mechanisms, as well as their applications in material synthesis, determination of reaction kinetics, and study of synthetic mechanisms.

Introduction

Microfluidic devices, which handle fluids with volumes typically ranging from microliters to picoliters, have spawned important applications in many research fields including biology, medicine, chemistry, and engineering sciences [1], [2], [3], [4], [5]. On these microscopic scales, the fluid behavior is primarily influenced by viscosity rather than inertia, and the ratio of surface area to volume becomes larger providing rapid heat and mass transfer [6]. These intrinsic properties make microfluidic techniques effective tools for applications such as chemical synthesis, study of reaction kinetics, biological sample preparation, and chemical and biological analyte detection [7]. As micro- and nano-fabrication techniques have matured, using microfluidic tools for synthesis has become more attractive with advantages of product uniformity, small footprint, precise control over reactions, and safer operation compared to large-scale reactors.

In the past several decades, a diverse range of microfluidic reactors have been designed for synthesis of a variety of functional materials [8]. Continuous-flow, droplet-based and digital microfluidics have been applied to produce materials with sizes ranging from nanometers to hundreds of micrometers, which have been considered broadly in several review papers [8], [9], [10], [11], [12], [13], [14]. Hydrodynamic focusing (HF) techniques are classified as continuous-flow microfluidics. Relative to droplet-based techniques, HF is straightforward to implement, and simple to simulate and understand because it is pure hydrodynamics that includes the surface tension effects at the liquid–liquid interface without the necessity of considering surface tension effects at the liquid-gas interface. HF techniques can accommodate high flow rates, rendering high-throughput applications possible. HF also enables highly controllable operational conditions owing to the fact that the flow behavior is the most influential parameter for synthesis and can be precisely controlled through varying flow rates. In fact, HF has been utilized for biological research long before the term “microfluidics” was coined. For example, commercial flow cytometers utilize HF for high-throughput single-cell analysis. Given the recent growth of research studies on materials synthesis by HF techniques, we focus this review on the advantages and challenges of this technique for materials synthesis, and to examine whether it is mature enough for industrial and clinic implementation or if there are further steps to be taken.

In this review, we outline the working principles of HF devices, describe materials synthesized through microfluidic HF techniques, and detail the applications in studies of reaction kinetics and synthesis mechanisms. Then, we compare HF technique with other microfluidic synthesis techniques, consider the advantages and limitations, and discuss the potential for HF techniques in the future.

Section snippets

Hydrodynamic focusing (HF) devices

Unlike macroscale fluid flow, which is generally turbulent, the flow in microfluidic channels falls into the laminar regime. In turbulent flow, inertial forces are dominant, while in laminar flow, the viscous forces are more prominent. Reynolds number (Re) is a measure of the ratio between inertial forces to viscous forces [15]:Re=ρuL/μwhere ρ is the fluid density, u is the mean fluid velocity and μ is the dynamic viscosity. Here L is the hydraulic diameter of the channel, which can be

Scale-up for mass production

Even though microfluidic HF devices can often synthesize nanomaterials superior to those derived from bulk synthesis, the associated throughput is generally much lower compared to batch processes. This is an inherent property of microfluidic systems because they are designed to handle minute amount of fluids in laminar flow regime which provides high uniformity and precise control of chemical compositions. In doing so, a typical microfluidic HF reactor can only synthesize NPs in tens of

Organic nanomaterials

Organic nanoparticles, such as polymer and lipid based NPs, often loaded with drugs, nucleic acids, or imaging components, are an important group of synthesized products that have great potential in the field of pharmaceutics and nanomedicine. The reduction in size to the nanoscale renders these particles bioavailable and targetable to specific tissues in biological systems. Polymer micro- and nanoparticles (NPs) are synthesized using photo-polymerization, precipitation, and crystallization,

Microfluidic HF devices for study of reaction mechanics

In addition to the synthesis of nanomaterials, microfluidic HF methods can be used as a tool to study the synthetic processes or chemical reaction kinetics. Conventionally, the study of reaction kinetics is performed in stopped-flow devices, while the reaction is triggered by a turbulent mixer. In this mode of operation, no meaningful measurement can be performed before completing the mixing, and this time period is call “dead time”. In conventional stopped-flow devices, the “dead time” is

Perspective

Microfluidic HF has proved itself as an economical, simple and powerful tool for the synthesis of nanomaterials with high monodispersity and reproducibility. On-chip HF devices have become popular due to their low cost, flexibility and ease of monitoring. 3D HF devices offer superior focusing performance compared to 2D HF devices by providing a highly uniform velocity profile and rapid mixing in the focused stream. Noting that, the on-chip 3D HF devices are still at their early stage due to the

Acknowledgments

Support from NIH (AI096305, HL109442, GM110494, GM112048, EB019785), NSF (IDBR-1455658), and W81XWH-12-1-0261 are acknowledged.

Mengqian Lu received her Bachelor degrees in Theoretical and Applied Mechanics and in Economics from Peking University in China in 2008. She joined the Department of Engineering Science and Mechanics at the Pennsylvania State University as a Ph. D. student in August 2008 the supervision of Professor Tony Jun Huang. She received her in 2014 from the Engineering Science and Mechanics at the Pennsylvania State University.

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    Mengqian Lu received her Bachelor degrees in Theoretical and Applied Mechanics and in Economics from Peking University in China in 2008. She joined the Department of Engineering Science and Mechanics at the Pennsylvania State University as a Ph. D. student in August 2008 the supervision of Professor Tony Jun Huang. She received her in 2014 from the Engineering Science and Mechanics at the Pennsylvania State University.

    Adem Ozcelik received his B.Sc. degree in Physics from Karadeniz Technical University, Turkey in 2006. He received his M.S. degree in Materials Science and Engineering and Ph.D. in Engineering Science and Mechanics from The Pennsylvania State University in 2016. Currently, He is working as ​Postdoctoral Associate in Mechanical Engineering and Materials Science Department at Duke University.

    Christopher L. Grigsby received his Ph.D. in Biomedical Engineering from Duke University. He will begin postdoctoral training as a fellow of the Whitaker International Program at Karolinska Institutet in Stockholm. His research interests include the nanomanufacturing of polymeric gene carriers and their applications in the field of cellular reprogramming.

    Yanhui Zhao received his bachelor degree from Zhejiang University at 2006. After that, he joined Institute of Optics and Electronics, Chinese Academy of Sciences for his master studies and graduated at 2009 with a presidential award for his research excellence. He received his Ph.D. in Engineering Science and Mechanics from The Pennsylvania State University in 2014 with his research topics focusing on interdisciplinary research concerning optics, nanotechnology, microfluidics, and fundamental biochemistry.

    Feng Guo received his B.S. degree in Physics from Wuhan University, China. In 2011, Feng received his Ph.D. from the Acoustofluidics Lab at the department of Engineering Science and Mechanics, The Pennsylvania State University in 2015. He has been conducting interdisciplinary research in the area of microfluidics, acoustics, cell biology and virology under the guidance of Dr. Tony Jun Huang. His primary research interest is in Acoustic tweezers, specifically, exploring the physics underlying the surface acoustic wave based acoustic manipulation, and applying the acoustic tweezer technology to cell–cell interaction, 3D bio-manufacturing, point-of-care diagnostic instrument.

    Kam W. Leong is the Samuel Y. Sheng Professor of Biomedical Engineering at Columbia University, with a joint appointment in the Department of Systems Biology at the Columbia University Medical Center. His research focuses on nanoparticle-mediated drug-, gene- and immuno-therapy, from design of new carriers to applications for cancer, hemophilia, infectious diseases, and cellular reprogramming. He is the Editor-in-Chief of Biomaterials, and a member of the National Academy of Inventors and the USA National Academy of Engineering.

    Tony Jun Huang is a professor at Department of Mechanical Engineering and Materials Science (MEMS) at Duke University. His research interests are in the fields of acoustofluidics, optofluidics, and micro/nano systems for biomedical diagnostics and therapeutics. He was elected a fellow of the following five professional societies: The American Institute for Medical and Biological Engineering (AIMBE), the American Society of Mechanical Engineers (ASME), the Institute of Electrical and Electronics Engineers (IEEE), the Institute of Physics (IOP), and the Royal Society of Chemistry (RSC).

    1

    These authors contributed equally to this work.

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