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Abstract

Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry.

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... Both lamination and chaotic advection ultimately require the construction of multi-layer channel devices with three-dimensional features, a significant challenge for microfabrication technologies. Previously, we introduced a system of discrete elements for assembling three-dimensional microfluidic circuits with integrated process sensors [13][14][15][16]. We leveraged additive manufacturing techniques (i.e. ...
... In designing discrete element microfluidics, two hydraulic terminal characteristics are of importance to designers: resistance to flow [13,14,17] and resident volume. The inherently parallel arrangement of the microfluidic network within both L1 and L2 elements implies that their hydraulic resistance is of minimum consequence to most networks of interest. ...
... The discrete microfluidic elements used in this study were manufactured using stereolithography from DSM Somos Watershed XC 11122 photoresin in the manner previously reported [13][14][15][16]18]. Microfluidic channels for all components were designed with 642.5 µm x 642.5 µm square cross sections, in keeping with the previously established standards.2 ...
Preprint
3D printing facilitates the straightforward construction of microchannels with complex three-dimensional architectures. Here, we demonstrate 3D-printed modular mixing components that operate on the basis of splitting and recombining fluid streams to decrease interstream diffusion length. These are compared to helical mixers that operate on the principle of chaotic advection.
... Although the implementation of multimaterial 3D printing has been realized in other AM techniques (e.g., DIW [75], FDM [76], and jetting [77]), only a few solutions for resin-vat-based polymerization techniques (e.g., multimaterial projection micro-stereolithography (MM PµSL)) are known. In general, three different approaches have been developed: (I) vat switching [78,79], (II) in situ material exchange through dynamic fluid control [38], and (III) the assembly of pre-printed parts ( Figure 2) [80][81][82]. ...
... Although the implementation of multimaterial 3D printing has been realized in other AM techniques (e.g., DIW [75], FDM [76], and jetting [77]), only a few solutions for resin-vat-based polymerization techniques (e.g., multimaterial projection micro-stereolithography (MM PµSL)) are known. In general, three different approaches have been developed: (I) vat switching [78,79], (II) in situ material exchange through dynamic fluid control [38], and (III) the assembly of pre-printed parts ( Figure 2) [80][81][82]. In 2011, Choi and coworkers introduced a custom-made 3D printer for processing different materials in a multimaterial approach [78]. ...
... The third example of multimaterial processing of polymers that can be used in multifunctional microfluidic device design does not rely on MM PµSL, but it contributes to the idea of multifunctional 3D-printed devices and is, therefore, discussed herein. The idea of prefabricated discrete elements assembled after the printing process was first proposed by Malmstadt and coworkers in 2014 [81]. The authors designed a library of different microfluidic elements and connectors that were reversibly connected, with the objective of fabricating truly complex microchannel systems. ...
Article
Full-text available
Droplet microfluidics—the art and science of forming droplets—has been revolutionary for high-throughput screening, directed evolution, single-cell sequencing, and material design. However, traditional fabrication techniques for microfluidic devices suffer from several disadvantages, including multistep processing, expensive facilities, and limited three-dimensional (3D) design flexibility. High-resolution additive manufacturing—and in particular, projection micro-stereolithography (PµSL)—provides a promising path for overcoming these drawbacks. Similar to polydimethylsiloxane-based microfluidics 20 years ago, 3D printing methods, such as PµSL, have provided a path toward a new era of microfluidic device design. PµSL greatly simplifies the device fabrication process, especially the access to truly 3D geometries, is cost-effective, and it enables multimaterial processing. In this review, we discuss both the basics and recent innovations in PµSL; the material basis with emphasis on custom-made photopolymer formulations; multimaterial 3D printing; and, 3D-printed microfluidic devices for emulsion formation as our focus application. Our goal is to support researchers in setting up their own PµSL system to fabricate tailor-made microfluidics.
... To enable the rapid deployment of customized microfluidic systems, the concept of "modular microfluidics" is proposed [16][17][18][19][20][21][22][23][24][25] . In modular microfluidics, individual microfluidic blocks are created in a modular design and assembled to form a system. ...
... Owing to this flexible design, modular microfluidics allows the design and reconfiguration of the microfluidics system during the postfabrication stage. In previous studies, microfluidic blocks were created in the form of jigsaw puzzle-like blocks 16,17 , Lego-like blocks 18,24,25 , magnetic blocks 22 , and other designs 19,23 to allow the versatile combination of different components. The modular microfluidics concept exhibits good adaptability in various applications and have become a promising approach for rapid on-site customization. ...
Article
Full-text available
A Rubik’s cube as a reconfigurable microfluidic system is presented in this work. Composed of physically interlocking microfluidic blocks, the microfluidic cube enables the on-site design and configuration of custom microfluidics by twisting the faces of the cube. The reconfiguration of the microfluidics could be done by solving an ordinary Rubik’s cube with the help of Rubik’s cube algorithms and computer programs. An O-ring-aided strategy is used to enable self-sealing and the automatic alignment of the microfluidic cube blocks. Owing to the interlocking mechanics of cube blocks, the proposed microfluidic cube exhibits good reconfigurability and robustness in versatile applications and proves to be a promising candidate for the rapid deployment of microfluidic systems in resource-limited settings.
... To enable the rapid deployment of customized microfluidic systems, the concept of "modular microfluidics" is proposed [16][17][18][19][20][21][22][23][24][25] . In modular microfluidics, individual microfluidic blocks are created in a modular design and assembled to form a system. ...
... Owing to this flexible design, modular microfluidics allows the design and reconfiguration of the microfluidics system during the postfabrication stage. In previous studies, microfluidic blocks were created in the form of jigsaw puzzle-like blocks 16,17 , Lego-like blocks 18,24,25 , magnetic blocks 22 , and other designs 19,23 to allow the versatile combination of different components. The modular microfluidics concept exhibits good adaptability in various applications and have become a promising approach for rapid on-site customization. ...
... The modular design is an inherent part of the AM technologies. SLA-printed polymeric discrete elements for 3D microfluidics with packaged connectors can be built as interlocking modules, and are easy to operate (Fig. 7g) [52]. Malmstadt et al. developed a sample library of standardized components and connectors to build large-scale microfluidic systems in 3D, which are modular and reconfigurable. ...
... f Reprinted from reference [51] with permission. g Reprinted from reference [52] with permission) 1 3 the spotlight with their capability to replicate organ-level functions by introducing cells into a microfluidic device that includes precisely fabricated chambers and channels. Chen et al. demonstrated cell-printed livers-on-chips by DLP-based 3D bioprinting (Fig. 9a) [57]. ...
Article
The use of microreactors in the continuous fluidic system has been rapidly expanded over the past three decades. Developments in materials science and engineering have accelerated the advancement of the microreactor technology, enabling it to play a critical role in chemical, biological, and energy applications. The emerging paradigm of digital additive manufacturing broadens the range of the material flexibility, innovative structural design, and new functionality of the conventional microreactor system. The control of spatial arrangements with functional printable materials determines the mass transport and energy transfer within architected microreactors, which are significant for many emerging applications, including use in catalytic, biological, battery, or photochemical reactors. However, challenges such as lack of design based on multiphysics modeling and material validation are currently preventing the broader applications and impacts of functional microreactors conjugated with digital manufacturing beyond the laboratory scale. This review covers a state-of-the-art of research in the development of some of the most advanced digital manufactured functional microreactors. We then the outline major challenges in the field and provide our perspectives on future research and development directions.
... The 3D printer uses colorless resin (proprietary) and comprises a modified acrylate oligomer and monomer, an epoxy monomer, a photoinitiator, and additives. Bhargava et al. build a 3D large-scale modular microfluidics system that comprises both T-junction and flow-focusing structures for droplet generation and sensing application, respectively (Fig. 4c) [163]. The design procedure was performed by FineLine Prototyping, Inc., using an SLA printer that employed a Somos WaterShed XC 11,122 photoresin. ...
... (n) Printed images of single-emulsion co-flow-based devices, five parallelized droplet generators, and double-emulsion co-flow-based devices. Figures are referenced in the same order as found above [157,[162][163][164][165][166][167][168][169][170][171][172][173][174] droplets with sizes varying from 150 to 1000 μm and CV < 10% (Fig. 4m). Similarly, Zhang et al. used a Nano Arch P140 (BMF Material Technology Inc., Shenzhen, China), which is based on the working principle of projection microstereolithography, for generating different types of emulsions (Fig. 4n) [174]. ...
Article
The advent of microfluidics, especially with the integration of droplet-based systems, has led to significant innovations and outstanding applications in many fields. While this field of study has grown increasingly over the years, the conventional method of fabricating these devices has discouraged their large-scale production, making their commercialization almost impossible. This is because traditional methods of producing droplet-based microfluidics are mostly time-consuming and labor-intensive and involve multiple processes. The emergence of 3D printing has found its application in microfluidics, providing an avenue for ease of fabrication with the aim of overcoming the limitations of conventional methods. While previous studies focused on studying the role of 3D printing in microfluidics, no study has categorically focused on the application of additive manufacturing to droplet-based microfluidics. This paper reviews the various 3D printing techniques associated with droplet-based microfluidics. Furthermore, we identify the salient features, limitations, and material properties of each printing technique while providing certain projections about their future application.
... Several types of 3D printing methods shows applicability and flexibility in view of microfluidic devices 35,36 . Many studies have reported the application to microfluidics [37][38][39] and furthermore utility for the fluid separation or manipulation 33,34,40,41 and diagnosis using biomarkers 40,42 . Bhargava et al. used 3D printing technology for fabricating a channel which can generate the liquid-liquid droplet 37 . ...
... Many studies have reported the application to microfluidics [37][38][39] and furthermore utility for the fluid separation or manipulation 33,34,40,41 and diagnosis using biomarkers 40,42 . Bhargava et al. used 3D printing technology for fabricating a channel which can generate the liquid-liquid droplet 37 . It implies the possibility of optical measurement through selecting the appropriate printing materials. ...
Article
Full-text available
The formation of droplets or bubbles in a microfluidic system is a significant topic requiring device miniaturization and a small volume of samples. Especially, a two-phase segmented flow can be applied to micro-mixing for chemical reactions and the treatment of heat and mass transfer. In this study, a flow of liquid slugs and bubbles was generated in a 3D-printed chip and controlled by a single pump creating a vacuum at the outlet. The pump and chip device were integrated to form a simple and portable system. The size and flow rate of liquid slugs, obtained through image processing techniques, were analyzed considering several parameters related to hydraulic resistance and pressure drop. In addition, the effect of segmentation on mixing was observed by measuring the intensity change using two different colored inks. The hydraulic resistance of air and liquid flows can be controlled by changing the tube length of air flow and the viscosity of liquid flow. Because the total pressure drop along the channel was produced using a single pump at the outlet of the channel, the size and flow rate of the liquid slugs showed a near linear relation depending on the hydraulic resistances. In contrast, as the total pressure varied with the flow rate of the pump, the size of the liquid slugs showed a nonlinear trend. This indicates that the frequency of the liquid slug formation induced by the squeezed bubble may be affected by several forces during the development of the liquid slugs and bubbles. In addition, each volume of liquid slug segmented by the air is within the range of 10–1 to 2 µL for this microfluidic system. The segmentation contributes to mixing efficiency based on the increased homogeneity factor of liquid. This study provides a new insight to better understand the liquid slug or droplet formation and predict the segmented flow based on the relationship between the resistance, flow rate, and pressure drop.
... Among the soft robots presented in this work, the constant flowbased soft robotic turtle is best suited to serve as a point of reference for comparing distinct methodologies for manufacturing fluidic circuit-based soft robots, as its oscillating behaviors are consistent with those often reported in the literature by other groups (15,17,(24)(25)(26)(27). For example, in contrast to soft lithography-based protocols previously used for fluidic circuit fabrication (13,(15)(16)(17), which typically necessitate technical training and access to microfabrication equipment and clean room facilities (19,52), access to a PolyJet 3D printer (either directly or through a commercial 3D printing service) represents the only critical barrier to reproducing all of the soft robots and integrated fluidic circuits reported here. Although the support material removal protocols of the presented PolyJet-based strategy require a degree of manual labor (on the order of tens of minutes, e.g., movie S7), the elimination of essentially all other manual fabrication, integration, and assembly procedures associated with soft robotic actuators, structural/body features, and fluidic circuitry is a central benefit. ...
Article
Full-text available
The emergence of soft robots has presented new challenges associated with controlling the underlying fluidics of such systems. Here, we introduce a strategy for additively manufacturing unified soft robots comprising fully integrated fluidic circuitry in a single print run via PolyJet three-dimensional (3D) printing. We explore the efficacy of this approach for soft robots designed to leverage novel 3D fluidic circuit elements—e.g., fluidic diodes, “normally closed” transistors, and “normally open” transistors with geometrically tunable pressure-gain functionalities—to operate in response to fluidic analogs of conventional electronic signals, including constant-flow [“direct current (DC)”], “alternating current (AC)”–inspired, and preprogrammed aperiodic (“variable current”) input conditions. By enabling fully integrated soft robotic entities (composed of soft actuators, fluidic circuitry, and body features) to be rapidly disseminated, modified on demand, and 3D-printed in a single run, the presented design and additive manufacturing strategy offers unique promise to catalyze new classes of soft robots.
... Potential solutions to overcome these problems stem from the use of modular microfluidic systems, in which different components are separated and individually designed and fabricated [22][23][24] . Here, we propose a modular approach with a multilayered configuration that separates the tissue chambers and culture medium channels into different device layers 25 , where both layers can be fabricated and modified individually. ...
Article
Full-text available
The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body. In this paper, a novel modular microfluidic system with a vertical two-layered configuration is developed to generate large-scale perfused microvascular networks in vitro. The two-layer polydimethylsiloxane (PDMS) configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly. This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities. The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction, serving as the interface between the medium channels and tissue chambers. Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels. Various large-scale microvascular networks were generated and quantified in terms of vessel length and density. Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers. This platform enables the culturing of interconnected, large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications, including basic biological studies and drug screening.
... These functions are achieved by a combination of passive and active microfluidic components. [68][69][70][71][72][73][74][75] Various microfluidic fabrication technologies have enabled the production of flow channels, culture chambers, membranes, and their complex combinations. These devices are usually passive. ...
Article
Full-text available
Microfluidic organs-on-chips (OoCs) technology has emerged as the trend for in vitro functional modeling of organs in recent years. Simplifying the complexities of the human organs under controlled perfusion of required fluids paves the way for accurate prediction of human organ functionalities and their response to interventions like exposure to drugs. However, in the state-of-the-art OoC, the existing methods to control fluids use external bulky peripheral components and systems much larger than the chips used in experiments. A new generation of compact microfluidic flow control systems is needed to overcome this challenge. This study first presents a structured classification of OoC devices according to their types and microfluidic complexities. Next, we suggest three fundamental fluid flow control mechanisms and define component configurations for different levels of OoC complexity for each respective mechanism. Finally, we propose an architecture integrating modular microfluidic flow control components and OoC devices on a single platform. We emphasize the need for miniaturization of flow control components to achieve portability, minimize sample usage, minimize dead volume, improve the flowing time of fluids to the OoC cell chamber, and enable long-duration experiments.
... Even if the current trend in the miniaturization of optical sensing is to bring the light source and the photon detector in the close vicinity of the interrogation sample, standard optical fibers are still used for those cases where robust modular systems are desired. Three-dimensional modular microfluidics has been recently introduced (Bhargava et al. 2014) as a methodology to overcome the issues appearing when monolithic design strategies fail. Modularity is one of the solutions envisaged for bringing microfluidic devices closer to its large-scale commercial implementation. ...
Article
Full-text available
Successful development of a micro-total-analysis system (µTAS, lab-on-a-chip) is strictly related to the degree of miniaturization, integration, autonomy, sensitivity, selectivity, and repeatability of its detector. Fluorescence sensing is an optical detection method used for a large variety of biological and chemical assays, and its full integration within lab-on-a-chip devices remains a challenge. Important achievements were reported during the last few years, including improvements of previously reported methodologies, as well as new integration strategies. However, a universal paradigm remains elusive. This review considers achievements in the field of fluorescence sensing miniaturization, starting from off-chip approaches, representing miniaturized versions of their lab counter-parts, continuing gradually with strategies that aim to fully integrate fluorescence detection on-chip, and reporting the results around integration strategies based on optical-fiber-based designs, optical layer integrated designs, CMOS-based fluorescence sensing, and organic electronics. Further successful development in this field would enable the implementation of sensing networks in specific environments that, when coupled to Internet-of-Things (IoT) and artificial intelligence (AI), could provide real-time data collection and, therefore, revolutionize fields like health, environmental, and industrial sensing.
... All components were designed using computer-aided design (CAD) software and printed using UnionTech Lite 600 (Union Tech, Inc., St. Charles, IL, USA) and WaterShed XC 11,122 resin (DSM Somos ® , Heerlen, Netherlands) in high-resolution mode. This nearly transparent resin provides well-characterized mechanical strength and good biocompatibility [22]. All components were designed with a square cross-sectional channel (1 cm × 1 cm) to ensure optical clarity through their interfaces, and each component is connected by a cylindrical regular connector or honeycomb screen connector. ...
Article
Full-text available
Zebrafish are a preferred vertebrate model for evaluating metabolism during development, and for toxicity studies. However, commercially available intermittent-flow respirometry systems (IFRS) do not provide a suitable zebrafish-scaled swimming tunnel with a low water volume and proper flow velocities. We developed a miniature IFRS (mIFRS) with a 3D-printed, palm-sized zebrafish treadmill for measuring the swimming ability and metabolic rate of a single one- or three-month-old zebrafish with and without toxicity treatment. The 3D-printed zebrafish treadmill consists of discrete components assembled together which enables the provision of a temporary closed circulating water flow. The results showed that three-month-old zebrafish of normal physiological status had higher energetic efficiency and could swim at a higher critical swimming speed (Ucrit) of 16.79 cm/s with a lower cost of transport (COTopt) of 0.11 μmol g-1m-1. However, for a single three-month-old zebrafish treated with an antibacterial agent, Ucrit decreased to 45% of normal zebrafish and the COTopt increased to 0.24 μmol g-1m-1, due to the impairment of mitochondria. Our mIFRS provides a low-cost, portable, and readily adaptable tool for studying the swimming performance and energetic metabolism of zebrafish.
... This process is still limited for small series production. [116]- [118] Papertouch ...
Thesis
The objective of this thesis is the development of a 6-axis robotic cell allowing the printing of electronic circuits on the surface of freeform objects and adapted to the prototyping and small series production of 3D objects integrating surface electronics.The manufacturing method proposed, from design to printing with a phase of scanning, mesh construction, circuit projection and speed analysis, is very useful for prototyping and small series applications where it is necessary to frequently change the substrate and the dimensions of the 3D object.An off-line programming approach allowing the printing of conductive trajectories on 3D objects and the automatic generation of the trajectory and the printing robot program has been developed. And a methodology to predict the circuit morphology by adapting the projection parameters according to the trajectory and the speed of the 6-axis robot has been proposed.A dedicated interface to manage the complete process has also been developed to control the printing process making it possible for people who are not experts in robotics to use the cell because its use does not require programming, the programs being generated automatically.Finally, prototypes were presented.
... Additive manufacturing has recently been used to create microfluidic devices, including complex 3D microfluidic circuits, droplet generators, gradient generators, and micro mixers [39][40][41]. This approach is very simple and eliminates the need for bonding; however, it is currently challenging for manufacturing microchannels with a cross-section area smaller than 500 µm × 500 μm [42]. ...
Article
Polydimethylsiloxane (PDMS) and polymethylmethacrylate (PMMA) are widely used in microfluidics, due to their excellent biocompatibility, high optical transparency, and ease of fabrication. This paper outlines a systematic approach to maximize the interfacial bonding strength between PDMS to PMMA. Fabrication parameters were studied by measuring bonding strength (i.e., burst test pressure) based on the Taguchi method. Under optimal bonding conditions, the microchannel assembly endured air pressure exceeding 770 kPa, liquid pressure exceeding 622 kPa, and tensile test exceeding 3,000 kPa. Bonding strength was sufficient to resist the entry of liquid at a rate of 6,800 times greater than the microchannel volume per minute. The ability to withstand such extremely high pressure without damage to the microdevices is an indication that interfacial bonding was indeed permanent. The proposed manufacturing method was also used to fabricate microfluidic devices capable of withstanding extremely high liquid pressure of 402 kPa, high flow rates exceeding 120 mL min⁻¹, and dense microchannels with gap of only 30μm. Finally, this proposed bonding process was used to fabricate a functional valve system of high-density configuration, which can be potentially used in microfluidics-based assays requiring high accuracy, rapid response, and the facile management of liquid transportation.
... One solution to this problem is through modularization. Instead of fabricating all microfluidic components on one single chip, the microfluidic network is constructed by assembling discrete modules sculped with basic microfluidic elements via standardized interconnects [20][21][22][23][24][25][26][27][28] . The modularization expedites design cycles and empowers customized microfluidics with its plug-and-play capability. ...
Article
Full-text available
Magnetic digital microfluidics (MDM) manipulates fluids in the form of droplets on an open substrate, and incorporates surface energy traps (SETs) to facilitate the droplet manipulation. Conventional MDM devices are fabricated monolithically, which makes it difficult to modify the device configuration without completely overhauling the original design. In this paper, we present a modular MDM architecture that enables rapid on-demand configuration and re-configuration of MDM platforms for customized bioanalyses. Each modular component contains a SET and a Lego-like antistud that fits onto a base board with Lego-like studs. We illustrate the versatility of the modular MDM architecture in biomarker sensing, pathogen identification, antibiotic resistance determination, and biochemical quantification by demonstrating immunoassays, phenotypical assays and enzymatic assays on various modular MDM platforms configured on demand to accomplish the fluidic operations required by assorted bioanalytical assays. The modular MDM architecture promises great potential for point-of-care diagnostics by offering on-demand customization of testing platforms for various categories of diagnostic assays. It also provides a new avenue for microfluidic assay development with its high configurability which would significantly reduce the time and cost of the development cycle.
... 3D Printing additive manufacturing has been identified as a progressive and effective technology and offer the possibility to rapidly and economically realize 25 complex 3D structures with different materials [19,20]. Since then, high-quality 3D printing microfluidics devices have been realized [21,22,23,24]. Additionally, some examples of micro-optofluidics systems based on specific realization protocols have been presented in [25,26].That underlines the potential of this technology for the lab-on-chip applications. ...
... Three-dimensional printed fittings and modules were designed and fabricated to produce single and compound emulsions using needles [33]; a modular device was produced using different printers, and compound emulsion generation was produced [34]. Moreover, a non-planar emulsion generator using T-junction structures was demonstrated using stereolithography (SLA) 3D printers [35,36]. In another study, fused filament fabrication was used to produce a droplet microfluidic device [37]. ...
Article
Full-text available
We report a microfluidic droplet generator which can produce single and compound droplets using a 3D axisymmetric co-flow structure. The design considered for the fabrication of the device integrated a user-friendly and cost-effective 3D printing process. To verify the performance of the device, single and compound emulsions of deionized water and mineral oil were generated and their features such as size, generation frequency, and emulsion structures were successfully characterized. In addition, the generation of bio emulsions such as alginate and collagen aqueous droplets in mineral oil was demonstrated in this study. Overall, the monolithic 3D printed axisymmetric droplet generator could offer any user an accessible and easy-to-utilize device for the generation of single and compound emulsions.
... Various 3D printing techniques (for example, inkjet printing, stereolithography, or fused deposition modeling) were already successfully applied to develop some MEMS devices. The exponential growth of scientific papers on 3D-printed microfluidic chips is observed during the last decade [10][11][12][13][14]. Additive manufacturing enables the fast and cost-effective development of truly threedimensional microfluidic structures. ...
Article
Full-text available
Three-dimensional (3D) printing is a powerful tool that enables the printing of almost unlimited geometry in a few hours, from a virtual design to a real structure. In this paper, we present a micro-electromechanical energy harvester that utilized a 3D printed micromechanical structure combined with a miniature permanent magnet and a microelectronic coil towards a hybrid electromagnetic vibrational hybrid energy harvester. Various micromechanical structure geometries were designed, printed, and tested. The characteristic dimensions of the springs were from 200 m to 400 m and the total volume of the devices was below 1 cm3. The resonant frequencies (95–340 Hz range), as well as bandwidths (6–23 Hz range), for the developed prototypes were determined. The maximal generated output power was almost 24 W with a power density up to almost 600 W/cm3.
... SLA-based manufacturing of constructs with microfluidic features were reported as early as 2014. 419 Now, with optimized SLA printing parameters and instrumentation (e.g., irradiation characteristics, light source path, digital micromirror device (DMD) pixel number), researchers could easily achieve sizes smaller than 100 μm for features such as 3D microchannels and even microneedles. 413,420−433 In addition, with the increasing availability of SLA-processable materials that match the optical and physical properties of PDMS, 424,434−438 SLA can potentially rival traditional soft lithography in fabricating on-chip microdevices that would be used for in vitro cellular studies. ...
... Other methods have been developed to facilitate the creation of 3D-printed microfluidics, including using a sacrificial molding (Therriault et al. 2003;Saggiomo and Velders 2015) or fugitive ink (He et al. 2015;Parekh et al. 2016;Kang et al. 2018) which prevent rapid reuse of the 3D printed molds, physically removing the mold (Hwang et al. 2015) which limits the geometries which can be constructed, or carefully tearing the PDMS while removing it from a 3D mold (Chan et al. 2015) which requires careful surface treatments. Significant progress has been made in using fully 3D printed microfluidics (Kitson et al. 2012;Au et al. 2014Au et al. , 2015Waheed et al. 2016;Morgan et al. 2016) including those assembled like Lego ® blocks (Bhargava et al. 2014;Vittayarukskul and Lee 2017;Nie et al. 2018), but the available materials still do not match the optical and chemical properties of monolithic PDMS. A 3D PDMS printer has been developed for bioprinting (Kolesky et al. 2014) where the resulting print has no voids and for use as a stereolithography resin (Femmer et al. 2014) but the PDMS had to be modified to no longer be optically clear. ...
Article
Full-text available
This paper describes a procedure to rapidly design and fabricate 3D microfluidic systems in the elastomer polydimethysiloxane (PDMS) using 3D molding, without the use of photolithography. A microfluidic system of channels is designed in a CAD program with the final fluid path being fully three dimensional. The initial design is inverted to create a negative mold which is 3D printed; the resolution of the printer is the limiting design factor. PDMS is cast in the 3D-printed mold in multiple pieces which are then cured together to create the final 3D device. No plasma bonding is required for the PDMS–PDMS sealing, a “glue” of uncured PDMS is used instead. A sample device of interlocking ring voids is presented to demonstrate the fabrication of a complex geometry which would be nearly impossible to manufacture via traditional soft lithography methods utilizing photolithography.
... When constrained by a diode, the switch in flow direction also enables negative conductance transitions. Our results demonstrate an approach for routing and switching in microfluidic networks through control mechanisms that are coded into the network structure, thus responding to the call for design strategies that allow diverse microfluidic systems to be assembled from a small set of core components [2,47]. ...
Preprint
Full-text available
Microfluidic systems are now being designed with precision to execute increasingly complex tasks. However, their operation often requires numerous external control devices due to the typically linear nature of microscale flows, which has hampered the development of integrated control mechanisms. We address this difficulty by designing microfluidic networks that exhibit a nonlinear relation between applied pressure and flow rate, which can be harnessed to switch the direction of internal flows solely by manipulating input and/or output pressures. We show that these networks exhibit an experimentally-supported fluid analog of Braess's paradox, in which closing an intermediate channel results in a higher, rather than lower, total flow rate. The harnessed behavior is scalable and can be used to implement flow routing with multiple switches. These findings have the potential to advance development of built-in control mechanisms in microfluidic networks, thereby facilitating the creation of portable systems that may one day be as controllable as microelectronic circuits.
... In such devices, modules are readily changed and reoriented to accommodate specific user needs. 69,[158][159][160][161] A recent demonstration includes a modular body-on-a-chip platform, where different organ-inspired chips are linked together to predict changes in drug levels and organ-specific toxicities quantitatively over time. 94 ...
This chapter provides an overview of the science, engineering, and design methods required in the development of micro/nanofluidic devices. Section 2 provides the scientific background of fluid mechanics and physical phenomena in micro/nanoscale. Section 3 gives a brief overview of the existing fabrication techniques employed in micro/nanofluidics. The techniques are grouped into three categories: (1) subtractive manufacturing, (2) formative manufacturing, and (3) additive manufacturing. The advantages and disadvantages of each manufacturing technique are also discussed. Implementation of the fluidic devices beyond laboratory demonstrations is not trivial, which requires a good understanding of the problems of interest and the end-users. To that end, Section 4 introduces the design thinking approach and its application to develop micro/nanofluidic devices. Finally, Section 5 concludes the chapter with future outlooks.
... In addition, Microfluidic Instrumentation Components (MFIC) have been recently developed, allowing assembly of discrete modules to form on-demand microfluidic systems. For instance, an open-source library of microfluidic modules that can be easily formed through stereo-lithography [173]. In this approach, an infra-red MFIC detection module was incorporated downstream from a droplet formation module of water in fluorocarbon oil, where a photo-transistor detects photonic absorbance changes for droplet detection and potential analysis. ...
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The integration of optical circuits with microfluidic lab-on-chip (LoC) devices has resulted in a new era of potential in terms of both sample manipulation and detection at the micro-scale. On-chip optical components increase both control and analytical capabilities while reducing reliance on expensive laboratory photonic equipment that has limited microfluidic development. Notably, in-situ LoC devices for bio-chemical applications such as diagnostics and environmental monitoring could provide great value as low-cost, portable and highly sensitive systems. Multiple challenges remain however due to the complexity involved with combining photonics with micro-fabricated systems. Here, we aim to highlight the progress that optical on-chip systems have made in recent years regarding the main LoC applications: (1) sample manipulation and (2) detection. At the same time, we aim to address the constraints that limit industrial scaling of this technology. Through evaluating various fabrication methods, material choices and novel approaches of optic and fluidic integration, we aim to illustrate how optic-enabled LoC approaches are providing new possibilities for both sample analysis and manipulation.
... One reaction to these three movements was the inception of modular microfluidics. For example, Bhargava and colleagues (28) proposed a modular microfluidic system in which discrete, sensor-embedding 3-D-printed fluidic modules can be assembled to form a complete system (Figure 1f ); Morgan and colleagues (29) utilized fused filament fabrication to propose a comparable modular microfluidic framework; Yuen and colleagues (30) described a similar system that utilizes leak-free magnetic interconnections to ease the assembly process; and Wang and colleagues (31) used randomly designed microfluidic circuits as elements in a desired application, generating a query database of thousands of numerically evaluated microfluidic designs from which a functional prototype for fabrication can be derived. While modular and random microfluidics offer significant advantages in terms of predictability and design time, they can rarely assemble an optimized system nor satisfy the requirements of demanding performance systems. ...
Article
Microfluidic devices developed over the past decade feature greater intricacy, increased performance requirements, new materials, and innovative fabrication methods. Consequentially, new algorithmic and design approaches have been developed to introduce optimization and computer-aided design to microfluidic circuits: from conceptualization to specification, synthesis, realization, and refinement. The field includes the development of new description languages, optimization methods, benchmarks, and integrated design tools. Here, recent advancements are reviewed in the computer-aided design of flow-, droplet-, and paper-based microfluidics. A case study of the design of resistive microfluidic networks is discussed in detail. The review concludes with perspectives on the future of computer-aided microfluidics design, including the introduction of cloud computing, machine learning, new ideation processes, and hybrid optimization. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 22 is June 4, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... 13−15 Droplets with pL−nL volumes can be passively generated by geometrical architectures 16−19 or actively generated by valves 20 and actuator-based platforms. 21,22 Droplet operations, such as merging, 23 splitting, 24 and trapping, 25,1,26 rely on specific geometrical features, which can be produced by advanced microfabrication techniques, such as soft lithography, 27 threedimensional (3D) printing, 28 laser cutting, 29 micromachining, 30 or injection molding. 31,32 These microfabrication methods can be expensive, time-consuming, or demand microfabrication expertise. ...
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Microsystem technologies allow a plethora of operations to be achieved for microemulsion- and microdroplet-based assays, providing miniaturized, yet large-throughput capabilities to assist experimentation in analytical chemistry, biology, and synthetic biology. Many of such approaches have been implemented on-chip, using microfluidic and lab-on-a-chip technologies. However, the microfabrication of such devices relies on expensive equipment and time-consuming methods, thus hindering their uptake and use by many research laboratories where microfabrication expertise is not available. Here, we demonstrate how fundamental water-in-oil microdroplet operations, such as droplet trapping, merging, diluting, and splitting, can be obtained using straightforward, inexpensive, and manually fabricated polymeric microtube modules. The modules are based on creating an angled tubing interface at the interconnection between two polymeric microtubes. We have characterized how the geometry and fluid dynamic conditions at this interface enabled different droplet operations to be achieved in a versatile and functional manner. We envisage this approach to be an alternative solution to expensive and laborious microfabrication protocols for droplet microfluidic applications.
Article
Modular concepts open a new way to create customized integrated microfluidic devices for the changing needs of users. However, easy-to-follow modular construction at the micro-scale remains a crucial challenge. Here, we present a one-step liquid molding based modular method. Liquid molding was coupled with standard SU-8 lithography to fabricate the connection adapters and the intricate micro-flow networks of modules. The connection adapter in each of the modules with three-dimensional topographic structures bridges the gap between the macroscopic world and the microfluidic network. Analogous to electronic circuits, individual functional components were assembled together via the standard fused silica capillary tubing in series or parallel, forming a leak-free integrated whole. The modular microfluidic circuits were further applied to pathogenic bacteria detection and parallel droplet generation. Via these applications, we demonstrated that modular circuits can be easily assembled and disassembled, thus enabling easy reconfiguration. Additionally, the ability to incorporate components made from different materials was exhibited.
Article
Microfluidic circuit on disk platform, also known as lab-on-a-disk, is an integrated system for automated high-throughput screening for biochemical analysis. The microfluidic circuit on disk is performing biochemical analysis through sequential processes such as filtration, separation, detection, and synthesis of reagents. Sequential processes in microfluidic circuit operate through the systematically linked components which include channel, valve, and chamber. The microchannel should has micrometer-scale for precise micro-liquid control in microfluidic circuit on disk. However, it is difficult to consider productivity together in the traditional technology. In addition, as the channel length increases, the microfluidic circuit requires much effort to construct components in a limited space of the disk. 3D printing is drawing attention to microfluidic channel fabrication technique in order to overcome the physical limitations in a traditional method. Components in microfluidic circuit can be individualized into each part, and it is possible to customize by reconfiguration of the microfluidic parts according to their application. Here, a 3D valve part in microfluidic circuit that controls switching micro-liquid is developed by using 3D printing technique. Micro-volume of liquid in a slope valve-equipped circuit is controlled over a wide range of angular velocities through slope angle variation. For sequential micro-volume of liquid control, three-line of assembled module is connected to a microfluidic circuit. In the microfluidic circuit with slope valves, the detection of fluorescent dye tagged-VEGF is possible through sequential mixing and reaction process. As a result, the micro-volume of liquid is successfully controlled with high accuracy using the 3D microfluidic circuit with slope valve.
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We introduce a microfluidic design that is desirable for three-dimensional (3D) micromanipulation, achieved through a set of double-layer channels with embedded symmetries. For the six-channel configuration, we show that a zero strain rate at the center of the device is protected by these symmetries, leading to a nonperturbative manipulation flow along any direction in 3D. We visualize such a nonperturbative flow structure through a finite element simulation and confirm this symmetry-protected strain-free condition. In addition to such 3D nonperturbative manipulations, we reveal two distinct perturbative flow modes available in this six-channel device, corresponding to a total of five independent modes that agrees with the degree-of-freedom counting. This symmetry-based micromanipulation is fully compatible with conventional microscopes and can be easily extended to other channel geometries for rich biological and physical applications.
Article
A three‐dimensional‐printed microfluidic device made of a thermoplastic material was used to study the creation of molecular filters by controlled dielectric breakdown. The device was made from acrylonitrile butadiene styrene by a fused deposition modeling three‐dimensional printer and consisted of two V‐shaped sample compartments separated by 750 µm of extruded plastic gap. Nanofractures were formed in the thin piece of acrylonitrile butadiene styrene by controlled dielectric breakdown by application voltage of 15–20 kV with the voltage terminated when reaching a defined current threshold. Variation of the size of the nanofractures was achieved by both variation of the current threshold and by variation of the ionic strength of the electrolyte used for breakdown. Electrophoretic transport of two proteins, R‐phycoerythrin (RPE; <10 nm in size) and fluorescamine‐labeled BSA (f‐BSA; 2–4 nm), was used to monitor the size and transport properties of the nanofractures. Using 1 mM phosphate buffer, both RPE and f‐BSA passed through the nanofractures when the current threshold was set to 25 µA. However, when the threshold was lowered to 10 µA or lower, RPE was restricted from moving through the nanofractures. When we increased the electrolyte concentration during breakdown from 1 to 10 mM phosphate buffer, BSA passed but RPE was blocked when the threshold was equal to, or lower than, 25 µA. This demonstrates that nanofracture size (pore area) is directly related to the breakdown current threshold but inversely related to the concentration of the electrolyte used for the breakdown process.
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With the rapid development of high technology, chemical science is not as it used to be a century ago. Many chemists acquire and utilize skills that are well beyond the traditional definition of chemistry. The digital age has transformed chemistry laboratories. One aspect of this transformation is the progressing implementation of electronics and computer science in chemistry research. In the past decade, numerous chemistry-oriented studies have benefited from the implementation of electronic modules, including microcontroller boards (MCBs), single-board computers (SBCs), professional grade control and data acquisition systems, as well as field-programmable gate arrays (FPGAs). In particular, MCBs and SBCs provide good value for money. The application areas for electronic modules in chemistry research include construction of simple detection systems based on spectrophotometry and spectrofluorometry principles, customizing laboratory devices for automation of common laboratory practices, control of reaction systems (batch- and flow-based), extraction systems, chromatographic and electrophoretic systems, microfluidic systems (classical and nonclassical), custom-built polymerase chain reaction devices, gas-phase analyte detection systems, chemical robots and drones, construction of FPGA-based imaging systems, and the Internet-of-Chemical-Things. The technology is easy to handle, and many chemists have managed to train themselves in its implementation. The only major obstacle in its implementation is probably one's imagination.
Chapter
Traditional in vitro and in vivo models typically used in cancer research have demonstrated a low predictive power for human response. This leads to high attrition rates of new drugs in clinical trials, which threaten cancer patient prognosis. Tremendous efforts have been directed towards the development of a new generation of highly predictable pre-clinical models capable to reproduce in vitro the biological complexity of the human body. Recent advances in nanotechnology and tissue engineering have enabled the development of predictive organs-on-a-chip models of cancer with advanced capabilities. These models can reproduce in vitro the complex three-dimensional physiology and interactions that occur between organs and tissues in vivo, offering multiple advantages when compared to traditional models. Importantly, these models can be tailored to the biological complexity of individual cancer patients resulting into biomimetic and personalized cancer patient-on-a-chip platforms. The individualized models provide a more accurate and physiological environment to predict tumor progression on patients and their response to drugs. In this chapter, we describe the latest advances in the field of cancer patient-on-a-chip, and discuss about their main applications and current challenges. Overall, we anticipate that this new paradigm in cancer in vitro models may open up new avenues in the field of personalized – cancer – medicine, which may allow pharmaceutical companies to develop more efficient drugs, and clinicians to apply patient-specific therapies.
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Droplet-based microfluidics offers an effective approach for overcoming the drawbacks of high viscosity and costs of ionic liquids (ILs) in practical applications. However, studies on the hydrodynamic behavior of the formation of IL-based Janus microdroplets which can facilitate the multifunctional applications of ILs through unique structures, are still limited due to their complex interfacial properties and high viscosities. Here, magnetic ionic liquid (MIL)-water Janus droplets were generated in an assembled co-flowing 3D-printed microchannel. Seven typical flow patterns of MIL-water Janus droplets generation were presented in a mountain-shaped flow pattern diagram, which was compared to the flow behavior of MIL single-phase droplet formation. The scaling law of MIL-water Janus droplet size was analyzed to further reveal the breakup mechanism of biphasic dispersed phases with large differences in viscosities and interfacial tensions. Besides, the morphology control of surfactant-free MIL-water Janus droplet in the microchannel was investigated qualitatively and quantitatively. And, by changing the continuous phase, the morphology evolution of MIL-water Janus droplet to core-shell structure was also observed. The present study would be useful for providing a deep and comprehensive understanding on the formation and structure control of IL-based Janus microdroplets which are promising candidates for the use in applications of catalysis and extraction.
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In the past decade, 3D printing technologies have been adopted for the fabrication of microfluidic devices. Extrusion-based approaches including fused filament fabrication (FFF), jetting technologies including inkjet 3D printing, and vat photopolymerization techniques including stereolithography (SLA) and digital light projection (DLP) are the 3D printing methods most frequently adopted by the microfluidic community. Each printing technique has merits toward the fabrication of microfluidic devices. Inkjet printing offers a good selection of materials and multimaterial printing, and the large build space provides manufacturing throughput, while FFF offers a great selection of materials and multimaterial printing but at lower throughput compared to inkjet 3D printing. Technical and material developments adopted from adjacent research fields and developed by the microfluidic community underpin the printing of sub-100 μm enclosed microchannels by DLP, but challenges remain in multimaterial printing throughput. With the feasibility of 3D printed microfluidics established, we look ahead at trends in 3D printing to gain insights toward the future of this technology beyond the sole prism of being an alternative fabrication approach. A shift in emphasis from using 3D printing for prototyping, to mimic conventionally manufactured outputs, toward integrated approaches from a design perspective is critically developed.
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Minimally invasive core needle biopsies for medical diagnoses have become increasingly common for many diseases. Although tissue cores can yield more diagnostic information than fine needle biopsies and cytologic evaluations, there is no rapid assessment at the point-of-care for intact tissue cores that is low-cost and non-destructive to the biopsy. We have developed a proof-of-concept 3D printed millifluidic histopathology lab-on-a-chip device to automatically handle, process, and image fresh core needle biopsies. This device, named CoreView, includes modules for biopsy removal from the acquisition tool, transport, staining and rinsing, imaging, segmentation, and multiplexed storage. Reliable removal from side-cutting needles and bidirectional fluid transport of core needle biopsies of five tissue types has been demonstrated with 0.5 mm positioning accuracy. Automation is aided by a MATLAB-based biopsy tracking algorithm that can detect the location of tissue and air bubbles in the channels of the millifluidic chip. With current and emerging optical imaging technologies, CoreView can be used for a rapid adequacy test at the point-of-care for tissue identification as well as glomeruli counting in renal core needle biopsies.
Fluidic systems are prevalent in many areas of science due to its advantage in miniaturization, development of unique tools for diseases diagnosis and biomolecule separation. In the chapter, we will describe some of the key features of microfluidic/nanofluidic (MF/NF) and lab-on-a-chip system in diverse field over the past years. In addition, we will highlight the major challenges for the microfluidic/nanofluidic and lab-on-a-chip system. All-purpose and universal micro/nanofluidic platforms that can perform multiplexed assays on real biological samples are in high demand. However, the adoption of novel microfluidic devices has been carried out at a slow pace due to translation gap in development of new devices to realization into commercialization. By addressing the challenges of system integration, low-cost technology availability, rapid regulatory approval, and clinical acceptance, a pipeline of promising microdevice technologies can be developed.
Chapter
Animal experiments and traditional two‐dimensional (2D) cell cultures have been considered essential tools for drug development. However, these platforms are showing striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms with higher relevancy to physiological conditions and better performance in simulation and prediction is desirable to facilitate drug development. As a versatile technology, 3D printing has been broadly involved in fields of biology and medicine. Recent advance in 3D bioprinting has enabled the precise manipulation of biological components, rendering it a promising technology for the construction of in vitro physiological and pathological models. This chapter presents the state‐of‐the‐art preclinical biomedical study and discusses the inadequacy of traditional experimental models. In particular, the meaning of constructing in vitro models is highlighted, focusing on the integration of 3D printing technology in the construction of such models. The in vitro models are generalized into three types: mini‐tissue, organ‐on‐a‐chip, and tissue/organ construct. The developing process of the in vitro models is introduced in detail, with relevant researches listed as illustrations. In particular, the present and potential grafting of 3D printing technology in constructing the in vitro models is reviewed.
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Microfluidics is an emerging technology of flow and control of fluids in microscale volume that offers highly specialized solutions to rapid, sensitive, non-invasive analysis and measurements in various engineering applications. When combined with microelectromechanical systems (MEMS), microfluidics technology has shown remarkable developments in small-scale devices for biosensing, chemical solutions, and precise detection of particles at a higher rate. MEMS–inspired microfluidics technology can contribute to the highly sensitive, recyclable, and portable sensing platforms for large-scale integration devices. In this review, we have surveyed the history and developmental phases occurring in MEMS are detailed. Finally, we conclude this review with future scope and guidelines for enabling the various approaches to overcome the obstacles and the mass commercialization of microfluidic devices. Recent applications of microfluidics in biosensing are also highlighted where research should be focused in the future. This article is protected by copyright. All rights reserved.
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Manipulating fluids at varying length scales and understanding their underlying mechanisms are significant for interdisciplinary studies of physics, chemistry, biology and engineering; fluid manipulation plays an important role in both scientific research and industrial applications. Here, we systematically review milli-, micro- and nanofluidics with dimensions ranging from millimeters to nanometers. The major physics associated with flow property and interactions of milli-, micro- and nanofluidics are discussed in detail, especially the differences arising from different length scales. Device fabrication techniques are summarized including additive and non-additive manufacturing methods for milli- and microfluidics and top-down and bottom-up strategies for nanofluidics. Recent developments and applications of milli-, micro- and nanofluidics are described to provide an overview on current researches. Outlooks of milli-, micro- and nanofluidics are discussed at the end.
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Droplet microfluidic devices are becoming essential platforms in chemical, material, biological and pharmaceutical applications, where small, highly controllable droplets and particles with uniform size are essential. Commonly used techniques for manufacturing these devices, such as lithography and high-speed milling, are expensive and time-consuming. In contrast, 3D printing provides a useful tool for the rapid production of cheap and sophisticated 3D droplet generators. We use fused filament fabrication (FFF) 3D printing technology to fabricate a customizable microfluidic device with droplet chips that can produce highly monodisperse droplets and emulsions. It is possible to generate W/O and O/W droplets with defined parameters by varying the channel diameter and the droplet chip geometry. The 3D-printed microfluidic device with different types of fluidic chips was successfully tested over a range of conditions. We used a computed tomography for the basic internal structure analysis of the microfluidic chip. The results are shown in this work point to significant potential applications of 3D-printing in droplet-based microfluidics production. Graphic abstract
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Microfluidic devices are constructed from polydimethylsiloxane (PDMS) due to their biocompatibility, fabrication ease, well-established protocols, and simplicity. PDMS-based microfluidic devices are constructed by (i) applying liquid PDMS to a negative mold (usually a silicon or 3D-printed mold) and (ii) curing the PDMS with heat exposure over a set time period. Unreacted resin monomers in 3D-printed molds prevent PDMS from fully curing, resulting in improper channel formation in PDMS and reducing the PDMS device’s efficacy. An in-house protocol that uses SU-8 as a “non-stick” coating on 3D-printed molds facilitates the successful casting of PDMS. Contact angle, surface profile, optical profile, and force testing prove that PDMS cast from SU-8-treated molds resembles pristine PDMS, unlike PDMS cast from untreated molds. Further, this method is generalized to commercial 3D prints using different 3D printing resins. To demonstrate this technique’s viability in microfluidic devices, a microfluidic tree using PDMS from treated 3D prints shows vibrant colors and clear lines. This is absent from an untreated PDMS.
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We study numerically the appearance and number of axial vortices in the outlets of X-shaped junctions of two perpendicular channels of rectangular sections with facing inlets. We explore the effect of the aspect ratio of the cross section, AR, on the number of vortices created at the center of the junction. Direct numerical simulations (DNSs) performed for different values of the Reynolds number Re and AR demonstrate that vortices with their axis parallel to the outlets, referred to as axial vortices, appear above critical Reynolds numbers Rec. As AR increases from 1 to 11, the number of vortices observed increases from 1 to 4, independently of Re. For AR = 1, the single axial vortex induces an interpenetration of the inlet fluids in the whole section; instead, for larger AR’s for which more vortices appear, the two inlet fluids remain largely segregated in bands, except close to the vortices. The linear stability analysis demonstrates that only one leading eigenmode is unstable for a given set of values of AR and Re. This mode provides a simplified model of the flow field, reproducing its key features such as the number of vortices and their distance. Its determination with this method requires a much smaller computational load than the DNS. This approach is shown to allow one to determine quickly and precisely the critical Reynolds number Rec and the sensitivity function S, which characterizes the influence of variations of the base flow on the unstable one.
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Despite the continuously increased requirement on automated synthesis of medicines for distributed manufacturing and personal care, it remains a challenge to realize automated synthesis which requires solid-liquid phase reactions. In this work, we demonstrated an automated solid-liquid synthesis for gadopentetate dimeglumine, the most widely used magnetic resonance imaging (MRI) contrast agent. The high-efficiency reaction was performed in a 3D microfluidic chip which was fabricated by femtosecond laser micromachining. The structure of the chip realized 3D shear flow which was essential for highly efficient mixing and movement of the solid-liquid mixtures. Ultraviolet visible (UV-vis) spectrometer was employed for in-line analysis to help automation of this system. Comparing with the round-bottom flask system, this synthetic system showed significantly higher reaction rate, indicating the advantage of the 3D microfluidic technology in micro chemical engineering.
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The last few decades have witnessed diversified in vitro models to recapitulate the architecture and function of living organs or tissues and contribute immensely to advances in life science. Two novel 3D cell culture models: 1) Organoid, promoted mainly by the developments of stem cell biology and 2) Organ‐on‐a‐chip, enhanced primarily due to microfluidic technology, have emerged as two promising approaches to advance the understanding of basic biological principles and clinical treatments. This review describes the comparable distinct differences between these two models and provides more insights into their complementarity and integration to recognize their merits and limitations for applicable fields. The convergence of the two approaches to produce multi‐organoid‐on‐a‐chip or human organoid‐on‐a‐chip is emerging as a new approach for building 3D models with higher physiological relevance. Furthermore, rapid advancements in 3D printing and numerical simulations, which facilitate the design, manufacture, and results‐translation of 3D cell culture models, can also serve as novel tools to promote the development and propagation of organoid and organ‐on‐a‐chip systems. Current technological challenges and limitations, as well as expert recommendations and future solutions to address the promising combinations by incorporating organoids, organ‐on‐a‐chip, 3D printing, and numerical simulation, are also summarized.
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Hydrogels are soft, water-based polymer gels that are increasingly used to fabricate free-standing fluidic devices for tissue and biological engineering applications. For many of these applications, pressurized liquid must be driven through the hydrogel device. To couple pressurized liquid to a hydrogel device, a common approach is to insert tubing into a hole in the gel; however, this usually results in leakage and expulsion of the tubing, and other options for coupling pressurized liquid to hydrogels remain limited. Here, we describe a simple coupling approach where microfluidic tubing is inserted into a plastic, 3D-printed bulb-shaped connector, which "pops" into a 3D-printed socket in the gel. By systematically varying the dimensions of the connector relative to those of the socket entrance, we find an optimal head-socket ratio that provides maximum resistance to leakage and expulsion. The resulting connection can withstand liquid pressures on the order of several kilopascals, three orders of magnitude greater than traditional, connector-free approaches. We also show that two-sided connectors can be used to link multiple hydrogels to one another to build complex, reconfigurable hydrogel systems from modular components. We demonstrate the potential usefulness of these connectors by established long-term nutrient flow through a 3D-printed hydrogel device containing bacteria. The simple coupling approach outlined here will enable a variety of applications in hydrogel fluidics.
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In the last few years, 3D printing has emerged as a promising alternative for the fabrication of microfluidic devices, overcoming some of the limitations associated with conventional soft-lithography. Stereolithography (SLA), extrusion-based technology, and inkjet 3D printing are three of the widely used 3D printing technologies owing to their accessibility and affordability. Microfluidic devices can be 3D printed by employing a manufacturing approach from four fundamental manufacturing approaches classified as (1) direct printing approach, (2) mold-based approach, (3) modular approach, and (4) hybrid approach. To evaluate the feasibility of 3D printing technologies for fabricating microfluidic devices, a review focused on 3D printing fundamental manufacturing approaches has been presented. Using a broad spectrum of additive manufacturing materials, 3D printed microfluidic devices have been implemented in various fields, including biological, chemical, and material synthesis. However, some crucial challenges are associated with the same, including low resolution, low optical transparency, cytotoxicity, high surface roughness, autofluorescence, non-compatibility with conventional sterilization methods, and low gas permeability. The recent research progress in materials related to additive manufacturing has aided in overcoming some of these challenges. Lastly, we outline possible implications of 3D printed microfluidics on the various fields of healthcare such as in vitro disease modeling and organ modeling, novel drug development, personalized treatment for cancer, and cancer drug screening by discussing the current state and future outlook of 3D printed ‘organs-on-chips,’ and 3D printed ‘tumor-on-chips.’ We conclude the review by highlighting future research directions in this field.
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The need to develop interest in STEM (science, technology, engineering, and mathematics) skills in young pupils has driven many educational systems to include STEM as a subject in primary schools. In this work, a science kit aimed at children from 8 to 14 years old is presented as a support platform for an innovative and stimulating approach to STEM learning. The peculiar design of the kit, based on modular components, is aimed to help develop a multitude of skills in the young students, dividing the learning process into two phases. During phase 1 the pupils build the experimental setup and visualize the scientific phenomena, while in phase 2, they are introduced and challenged to understand the principles on which these phenomena are based, guided by a handbook. This approach aims at making the experience more inclusive, stimulating the interest and passion of the pupils for scientific subjects.
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We have demonstrated the application of low surface energy fluoropolymer coatings onto poly(dimethylsiloxane) (PDMS) microfluidic devices for droplet formation and extraction-induced merger of droplets. Initiated chemical vapor deposition (iCVD) was used to pattern fluoropolymer coatings within microchannels based on geometrical constraints. In a two-phase flow system, the range of accessible flow rates for droplet formation was greatly enhanced in the coated devices. The ability to controllably apply the coating only at the inlet facilitated a method for merging droplets. An organic spacer droplet was extracted from between a pair of aqueous droplets. The size of the organic droplet and the flow rate controlled the time to merge the aqueous droplets; the process of merging was independent of the droplet sizes. Extraction-induced droplet merging is a robust method for manipulating droplets that could be applied in translating multi-step reactions to microfluidic platforms.
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The vast majority of microfluidic devices are developed in PDMS by molding ("soft lithography") because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices.
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Abstract Microfluidic devices for manipulating fluids are widespread and finding uses in many scientific and industrial contexts. Their design often requires unusual geometries and the interplay of multiple physical effects such as pressure gradients, electrokinetics, and capillarity. These circumstances lead to interesting variants of well-studied fluid dynamical problems and some new fluid responses. We provide an overview of flows in microdevices with focus on electrokinetics, mixing and dispersion, and multiphase flows. We highlight topics important for the description of the fluid dynamics: driving forces, geometry, and the chemical characteristics of surfaces.
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We present a combinatorial dilution device using a three-layer microfluidic network that can produce systematic variations of buffer and additive solutions in a combinatorial fashion for high throughput screening and optimization. A proof-of-concept device providing seven combinations (ABC/D, AB/D, BC/D, AC/D, A/D, B/D, and C/D) of three additive samples (A, B, and C) into a buffer solution (D) has been demonstrated. Such combinations are often used in simplex-centroid mixture DOE (design of experiments), useful techniques to minimize the experimental efforts at maximal information output with systematic variations of large-scale components. Based on mathematical and electrical modeling and computational fluid dynamic simulation, the device has been designed, fabricated, and characterized. KeywordsCombinatorial device-Microfluidic network-High throughput screening-Design of experiments
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In this Technical Note, for the first time, a truly "plug-n-play" modular microfluidic system (SmartBuild Plug-n-Play Modular Microfluidic System) is presented for designing and building integrated modular microfluidic systems for biological and chemical applications. The modular microfluidic system can be built by connecting multiple microfluidic components together to form a larger integrated system. The SmartBuild System comprises of a motherboard with interconnect channels/grooves, fitting components, microchannel inserts with different configurations and microchips/modules with different functionalities. Also, heaters, micropumps and valving systems can be designed and used in the system. Examples of an integrated mixing system and reaction systems are presented here to demonstrate the versatility of the SmartBuild System.
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Theoretical Microfluidics
  • Bruus
Bruus H (2008) Theoretical Microfluidics, Oxford Master Series in Condensed Matter Physics (Oxford Univ Press, Oxford), Vol 18.