skip to main content


Title: Toward Deterministic Lateral Displacement-Based Continuous-Flow Microfluidic Particle Reactors via Direct Laser Writing
Multi-stage fluidic reaction schemes for suspended particles (e.g., micro/nanospheres, cells, bacterial species, and extracellular vesicles) underly a diversity of chemical and biological applications. Conventional methods for executing such protocols can be exceedingly time, labor, and/or cost intensive. Microfluidic strategies can address these drawbacks; however, such technologies typically rely on clean room-based microfabrication that suffer from similar deficits for manufacturing the chips. To simultaneously overcome these challenges, here we explore the use of the submicron-scale additive manufacturing approach, “Two-Photon Direct Laser Writing (DLW)”, as a means for fabricating micro-fluidic “Deterministic Lateral Displacement (DLD)” arrays capable of passively guiding suspended particles across discrete, adjacent flow streams—the fundamental capability of continuous-flow multi-stage particle microreactors. Experimental results from microfluidic experimentation with 5 μm-in-diameter fluorescent particles revealed effective particle transport across flow streams, with 87.5% of fluorescent peaks detected in the designated, opposing outlet following the DLD array. These results suggest utility of the presented approach for micro- and nanoparticle-based microfluidic reactors targeting wide-ranging chemical and biological applications.  more » « less
Award ID(s):
1761395
NSF-PAR ID:
10376837
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
Proceedings of the 20th Solid-State Sensors, Actuators and Microsystems Workshop (Hilton Head Workshop 2022)
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Microfluidic devices manufactured from soft polymeric materials have emerged as a paradigm for cheap, disposable and easy-to-prototype fluidic platforms for integrating chemical and biological assays and analyses. The interplay between the flow forces and the inherently compliant conduits of such microfluidic devices requires careful consideration. While mechanical compliance was initially a side-effect of the manufacturing process and materials used, compliance has now become a paradigm, enabling new approaches to microrheological measurements, new modalities of micromixing, and improved sieving of micro- and nano-particles, to name a few applications. This topical review provides an introduction to the physics of these systems. Specifically, the goal of this review is to summarize the recent progress towards a mechanistic understanding of the interaction between non-Newtonian (complex) fluid flows and their deformable confining boundaries. In this context, key experimental results and relevant applications are also explored, hand-in-hand with the fundamental principles for their physics-based modeling. The key topics covered include shear-dependent viscosity of non-Newtonian fluids, hydrodynamic pressure gradients during flow, the elastic response (deformation and bulging) of soft conduits due to flow within, the effect of cross-sectional conduit geometry on the resulting fluid–structure interaction, and key dimensionless groups describing the coupled physics. Open problems and future directions in this nascent field of soft hydraulics, at the intersection of non-Newtonian fluid mechanics, soft matter physics, and microfluidics, are noted. 
    more » « less
  2. null (Ed.)
    Additive manufacturing (or "three-dimensional (3D) printing") technologies offer unique means to expand the architectural versatility with which microfluidic systems can be designed and constructed. In particular, "direct laser writing (DLW)" supports submicron-scale 3D printing via two-photon (or multi-photon) polymerization; however, such high resolutions are poorly suited for fabricating the macro-to-micro interfaces (i.e., fluidic access ports) critical to microfluidic applications. To bypass this issue, here we present a novel strategy for using DLW to 3D print architecturally complex microfluidic structures directly onto-and notably, fully integrated with-macroscale fused silica tubes. Fabrication and experimental results for this "ex situ DLW (esDLW)" approach revealed effective structure-to-tube sealing, with fluidic integrity maintained during fluid transport from macroscale tubing, into and through demonstrative 3D printed microfluidic structures, and then out of designed outlets. These results suggest that the presented DLW-based printing approach for externally coupling microfluidic structures to macroscale fluidic systems holds promise for emerging applications spanning chemical, biomedical, and soft robotics fields. 
    more » « less
  3. Metal-mediated cross-coupling reactions offer organic chemists a wide array of stereo- and chemically-selective reactions with broad applications in fine chemical and pharmaceutical synthesis.1 Current batch-based synthesis methods are beginning to be replaced with flow chemistry strategies to take advantage of the improved consistency and process control methods offered by continuous flow systems.2,3 Most cross-coupling chemistries still encounter several issues in flow using homogeneous catalysis, including expensive catalyst recovery and air sensitivity due to the chemical nature of the catalyst ligands.1 To mitigate some of these issues, a ligand-free heterogeneous catalysis reaction was developed using palladium (Pd) loaded into a polymeric network of a silicone elastomer, poly(hydromethylsiloxane) (PHMS), that is not air sensitive and can be used with mild reaction solvents (ethanol and water).4 In this work we present a novel method of producing soft catalytic microparticles using a multiphase flow-focusing microreactor and demonstrate their application for continuous Suzuki-Miyaura cross-coupling reactions. The catalytic microparticles are produced in a coaxial glass capillary-based 3D flow-focusing microreactor. The microreactor consists of two precursors, a cross-linking catalyst in toluene and a mixture of the PHMS polymer and a divinyl cross-linker. The dispersed phase containing the polymer, cross-linker, and cross-linking catalyst is continuously mixed and then formed into microdroplets by the continuous phase of water and surfactant (sodium dodecyl sulfate) introduced in a counter-flow configuration. Elastomeric microdroplets with a diameter ranging between 50 to 300 micron are produced at 25 to 250 Hz with a size polydispersity less than 3% in single stream production. The physicochemical properties of the elastomeric microparticles such as particle swelling/softness can be tuned using the ratio of cross-linker to polymer as well as the ratio of polymer mixture to solvent during the particle formation. Swelling in toluene can be tuned up to 400% of the initial particle volume by reducing the concentration of cross-linker in the mixture and increasing the ratio of polymer to solvent during production.5 After the particles are produced and collected, they are transferred into toluene containing palladium acetate, allowing the particles to incorporate the palladium into the polymer network and then reduce the palladium to Pd0 with the Si-H functionality present on the PHMS backbones. After the reduction, the Pd-loaded particles can be washed and dried for storage or switched into an ethanol/water solution for loading into a micro-packed bed reactor (µ-PBR) for continuous organic synthesis. The in-situ reduction of Pd within the PHMS microparticles was confirmed using energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and focused ion beam-SEM, and TEM techniques. In the next step, we used the developed µ-PBR to conduct continuous organic synthesis of 4-phenyltoluene by Suzuki-Miyaura cross-coupling of 4-iodotoluene and phenylboronic acid using potassium carbonate as the base. Catalyst leaching was determined to only occur at sub ppm concentrations even at high solvent flow rates after 24 h of continuous run using inductively coupled plasma mass spectrometry (ICP-MS). The developed µ-PBR using the elastomeric microparticles is an important initial step towards the development of highly-efficient and green continuous manufacturing technologies in the pharma industry. In addition, the developed elastomeric microparticle synthesis technique can be utilized for the development of a library of other chemically cross-linkable polymer/cross-linker pairs for applications in organic synthesis, targeted drug delivery, cell encapsulation, or biomedical imaging. References 1. Ruiz-Castillo P, Buchwald SL. Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions. Chem Rev. 2016;116(19):12564-12649. 2. Adamo A, Beingessner RL, Behnam M, et al. On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system. Science. 2016;352(6281):61 LP-67. 3. Jensen KF. Flow Chemistry — Microreaction Technology Comes of Age. 2017;63(3). 4. Stibingerova I, Voltrova S, Kocova S, Lindale M, Srogl J. Modular Approach to Heterogenous Catalysis. Manipulation of Cross-Coupling Catalyst Activity. Org Lett. 2016;18(2):312-315. 5. Bennett JA, Kristof AJ, Vasudevan V, Genzer J, Srogl J, Abolhasani M. Microfluidic synthesis of elastomeric microparticles: A case study in catalysis of palladium-mediated cross-coupling. AIChE J. 2018;0(0):1-10. 
    more » « less
  4. Abstract

    Silver nanoparticles (AgNP) can help prevent infection of virus and bacteria. The size and morphology of AgNP can be crucial to function, with smaller nanoparticles (< 20 nm) able to penetrate the cell wall. This is significant as oxidative stress and genotoxicity are associated with some sizes and coatings of AgNP, contraindicating the use of AgNP to reduce infection. We present evidence that a microfluidic chip can synthesize larger sizes and distributions of AgNP from the nano-to-micro size range. We show results from a microfluidic mixing chip that can produce a wide range of nano-to-micro size (~ 24–400 nm) AgNP. Synthesis is based on a modified Turkevich method, using a single-step AgNP synthesis on the microfluidic chip using two chemical components, trisodium citrate (NaCit) and AgNO3. To make AgNP more accessible, we describe the microfluidic chip and conditions capable of synthesis. We also describe how modification of flow rate and chemical reagent concentration change particle diameter during production. In our experiments, we found that AgNP production created a visible adsorption line in the microfluidic device, possibly owing to AgNP surface interaction at the polydimethylsiloxane (PDMS) interface. We characterize these particles with dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Based on optical light microscopy, we hypothesize that AgNP formation primarily occurs at the interface between the two chemical reagent streams. We also conclude that AgNP size increases could be due to interaction with the PDMS surface, which is known to be porous. Future work will help to understand how surface interaction may influence the formation of larger particles.

     
    more » « less
  5. Abstract

    Circulating Tumor Cells (CTCs), which migrate from original sites in a body to distant organs through blood, are a key factor in cancer detection. Emerging Label-free techniques owing to their inherent advantage to preserve characteristics of sorted cells and low consumption of samples can be promising to the prediction of cancer progression and metastasis research. Deterministic Lateral Displacement (DLD) is one of the label-free separation techniques employing a specific arrangement of micro-posts for continuous separation of suspended cells in a buffer based on the size of cells. Separation based solely on size is challenging since the size distributions of CTCs might overlap with those of normal blood cells. To address this problem, DLD can be combined with dielectrophoresis (DEP) technique which is the phenomenon of particle movement in a non-uniform electric field owing to the polarization effect. Although, DLD devices employ the laminar flow in low Reynolds number (Re) fluid flow due to predictability of such flow regimes, they should be improved to work in higher Re flow regime so as to attain high throughput devices. In this paper, a particle tracing simulation is developed to study the effects of different post shapes, shift fraction of micropost arrays, and dielectrophoresis forces on separation of CTCs from peripheral blood cells. Our numerical model and results provide a groundwork for design and fabrication of high-throughput DLD-DEP devices for improvement of CTC separation.

     
    more » « less