Microfluidic Community Research Articles

Open-Source Pressure Controller Based on Compact Electro-Pneumatic Regulators for Droplet Microfluidics Applications

Microfluidics is a rapidly growing area that provides innovations in biotechnology, medical diagnostics, and life science. Along with the commercial solutions, there are open-source projects aimed to make such technologies more affordable and flexible for end users. In this article, we developed an open-source, low-cost, and easy-to-use microfluidic pressure controller with a modular design based on electropneumatic regulators to introduce liquids into microfluidic devices under constant pressures. For implementation of complex experimental protocols, the controller contains a vacuum pump, relay outputs, analog inputs, and digital inputs/outputs to connect external equipment. It can be operated using five displays and an encoder or from a personal computer in a manual or automatic regime through the custom open-source software. In this study, we applied this pressure controller for the generation of water-in-oil droplets in microfluidic flow-focusing droplet generators. Droplets&#x2019; diameters linearly depended on the dispersed and continuous phases&#x2019; ratio in the range 5&#x2013;<inline-formula> <tex-math notation="LaTeX">$65 \mu \text{m}$ </tex-math></inline-formula>. In all the cases, the generation regimes were stable for at least 4 h. Direct comparison of the droplet generation obtained with the developed pressure controller and precise syringe pumps showed that it will suit the needs of the microfluidic community for different flow-based lab-on-a-chip applications, as a more affordable and flexible solution for introducing liquids and controlling flow sensors, heaters, valves, light sources, and so on during experiments.

Fabrication of PDMS microfluidic devices using nanoclay-reinforced Pluronic F-127 as a sacrificial ink

Additive manufacturing or three-dimensional (3D) printing technology is increasingly being employed in biochemical as well as clinical applications and more importantly in fabrication of microfluidic devices. However, the microfluidic community mainly relies on photolithography for fabrication of a defined mask, which is both tedious and expensive requiring clean room settings as well as limited to the generation of two-dimensional features. In this work, we 3D printed nanoclay-reinforced Pluronic ink as a sacrificial material, which exhibited shear thinning behavior and superior printability allowing the fabrication of unsupported or overhanging templates of channels with uniform diameter and circular cross-sections. To highlight the potential and effectiveness of the presented approach, we fabricated a human blood vessel-on-a-chip model with curved as well as straight channels. These channels were then lined up with human umbilical vein endothelial cells (HUVECs) and subjected to a dynamic culture for 10 d to explore the effect of shear stress on HUVEC morphology based on the location of HUVECs in the devices. Overall, we presented a highly affordable, practical and useful approach in manufacturing of polydimethylsiloxane-based devices with closed microfluidic channels, which holds great potential for a numerous applications, such as but not limited to organ-on-a-chip, microfluidics, point-of-care devices and drug screening platforms.

Automated calibration of 3D-printed microfluidic devices based on computer vision.

With the development of 3D printing techniques, the application of it in microfluidic/Lab-on-a-Chip (LoC) fabrication is becoming more and more attractive. However, to achieve a satisfying printing quality of the target devices, researchers usually require quite an amount of work in calibration trials even for high-end 3D printers. To increase the calibration efficiency of the average priced printers and promote the application of 3D printing technology in the microfluidic community, this work has presented a computer vision (CV)-based method for rapid and precise 3D printing calibration with examples on cylindrical hole/post diameters of 0.2-2.4 mm and rectangular hole/post widths of 0.2-1.0 mm by a stereolithography-based 3D printer. Our method is fully automated, which contains five steps and only needs a camera at hand to provide photos for convolutional neural network recognition. The experimental results showed that our CV-based method could provide calibrated dimensions with just one print of the specific calibration ruler to meet user desire. The higher resolution of the photo provides a higher precision in calibration. Subsequently, only one more print for the target device is needed after the calibration process. Overall, this work has provided a quick and precise calibration tool for researchers to apply 3D printing in the fabrication of their microfluidic/LoC devices with average price printers. Besides, with our open source calibration software and calibration ruler design file, researchers can modify the specific setting based on customized needs and conduct calibration on any type of 3D printer.

3D Printing: An Alternative Microfabrication Approach with Unprecedented Opportunities in Design.

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.

3D Printing of Inertial Microfluidic Devices

Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.

In Situ Fine‐Tuning of Microfluidic Chips by Swelling and Its Application to Droplet Microfluidics

AbstractOver the last two decades, polydimethylsiloxane (PDMS) has been widely used as the material of choice for fast‐throughput prototyping of microfluidic devices due to the ease of fabrication of PDMS devices by soft‐lithography replica molding methods. Nevertheless, PDMS is known to swell significantly in a variety of organic solvents which has sometimes limited its use in synthetic chemistry and has led the microfluidic community to consider PDMS as being “incompatible” with such solvents. Nevertheless, as shown here, when analyzed deeper and controlled properly, the solvent‐induced swelling of PDMS actually constitutes a potentially useful phenomenon that can become a simple tool to control and adjust finely and dynamically the geometry of microfluidic chips in situ. In this paper, this method is applied to the control of the behavior of a variety of droplet generators. The simplicity and efficiency of this approach make it a great asset for droplet microfluidics synthesis, for which microreactor sizes are a critical parameter that is often overlooked due to its complex implementation. In a more general sense, it is expected that integrating swelling into design should allow to adjust the function of many different types of chips exhibiting geometry‐driven functions.

On hybrid electroosmotic kinetics for field-effect-reconfigurable nanoparticle trapping in a four-terminal spiral microelectrode array.

Induced-charge electroosmosis (ICEO) has attracted tremendous popularity for driving fluid motion from the microfluidic community since the last decade, while less attention has been paid to ICEO-based nanoparticle manipulation. We propose herein a unique concept of hybrid electroosmotic kinetics (HEK) in terms of bi-phase ICEO (BICEO) actuated in a four-terminal spiral electrode array, for effective electrokinetic enrichment of fluorescent polystyrene nanoparticles on ideally polarizable metal strips. First, by alternating the applied AC voltage waves between consecutive discrete terminals, the flow stagnation lines where the sample nanoparticles aggregate can be switched in time between two different distribution modes. Second, we innovatively introduce the idea of AC field-effect flow control on BICEO; by altering the combination of gating voltage sequence, not only the number of circulative particle trapping lines is doubled, but the collecting locations can be flexibly reconfigured as well. Third, hydrodynamic streaming of DC-biased BICEO is tested in our device design, wherein the global linear electroosmosis dominates BICEO contributed from both AC and DC components, resulting in a reduction of particle enrichment area, while with a sharp increase in sample transport speed inside the bulk phase. The flow field associated with HEK is predicted using a linear asymptotic analysis under Debye-Huckel limit, with the simulation results in qualitative agreement with in-lab observations of nanoparticle trapping by exploiting a series of improved ICEO techniques. This work provides an affordable and field-deployable platform for real-time nanoparticle trapping in the context of dilute electrolyte.

On traveling-wave field-effect flow control for simultaneous induced-charge electroosmotic pumping and mixing in microfluidics: physical perspectives and theoretical analysis

Since its first proposition at the end of the last century (Schasfoort et al 1999 Science 286 942–5), field-effect flow control at micrometer dimensions has attracted tremendous attention from the microfluidic community. Most previous research on this subject has mainly focused on enhancing the electroosmotic pump flow rate by introducing an additional in-phase counterionic charge across the diffusing screening cloud with external gate electrodes of static DC voltages. However, there is a flaw, namely that AC fields, which suppress undesirable electrochemical reactions, result in zero time-averaged flow. Starting from this point, we present herein a brand new approach to traveling-wave field-effect electroosmosis control from a theoretical point of view, in the context of a smart manipulation tool for the stratified liquid content of miniaturization systems. In the configuration of a traveling-wave flow field-effect transistor (TW-FFET), the field-induced out-of-phase Debye screening charge within the thin double layer originates from the forward propagation of a traveling potential wave along a discrete arrangement of external gating electrode arrays, which interacts actively with the horizontal standing-wave electric field imposed across the source–drain terminal. Since the voltage waves and induced free charge are all sinusoidal functions of the observation time, the net ICEO flow component can survive in a broad frequency range. Due to the action of the background AC electric field on the inhomogeneous counterionic charge induced at the solution/sidewall interface, asymmetric ICEO vortex patterns appear above the traveling-wave gate arrays, giving rise to simultaneous induced-charge electroosmotic pumping and mixing of fluidic samples. A mathematical model is then developed to numerically investigate the feasibility of TW-FFETs in electrokinetic microflow manipulation. A prototyping paradigm of fully electrokinetics-driven microfabricated fluidic networks in a cross shape is theoretically erected, with four sets of gating traveling-fields in perpendicular orientations, from which the resulting liquid mixture is obtainable at any one of the three outlet ports. Supported by mathematical analysis, our physical demonstration of the TW-FFET shows it has great potential to advance fully automated electroconvective sample treatment in modern micro total analytical systems.

On AC-Field-Induced Nonlinear Electroosmosis next to the Sharp Corner-Field-Singularity of Leaky Dielectric Blocks and Its Application in on-Chip Micro-Mixing.

Induced-charge electroosmosis has attracted lots of attention from the microfluidic community over the past decade. Most previous researches on this subject focused on induced-charge electroosmosis (ICEO) vortex streaming actuated on ideally polarizable surfaces immersed in electrolyte solutions. Starting from this point, we conduct herein a linear asymptotic analysis on nonlinear electroosmotic flow next to leaky dielectric blocks of arbitrary electrical conductivity and dielectric permittivity in harmonic AC electric fields, and theoretically demonstrate that observable ICEO fluid motion can be generated at high field frequencies in the vicinity of nearly insulating semiconductors, a very low electrical conductivity, of which can evidently increase the double-layer relaxation frequency (inversely proportional to the solid permittivity) to be much higher than the typical reciprocal RC time constant for induced double-layer charging on ideally polarizable surfaces. A computational model is developed to study the feasibility of this high-frequency vortex flow field of ICEO for sample mixing in microfluidics, in which the usage of AC voltage signal at high field frequencies may be beneficial to suppress electrochemical reactions to some extent. The influence of various parameters for developing an efficient mixer is investigated, and an integrated arrangement of semiconductor block array is suggested for achieving a reliable mixing performance at relatively high sample fluxes. Our physical demonstration with high-frequency ICEO next to leaky dielectric blocks using a simple channel structure offers valuable insights into the design of high-throughput micromixers for a variety of lab-on-a-chip applications.

Application of polydopamine in biomedical microfluidic devices

Polydopamine (PDA) is a bioinspired material with tremendous potential for applications involving surface modifications. By simply immersing the substrate in the dopamine monomer solution, we are able to apply a hydrophilic and biofunctional PDA coating that adheres strongly to any surface, including (super)hydrophobic surface, with unprecedented ease. Using PDA, almost any materials can be immobilized on the surface in a single step by mixing them with the dopamine monomer solution. This review provides a comprehensive coverage of the applications of PDA in the device fabrication, surface modification, and biofunctionalization of biomedical microfluidic devices. While discussing the advantages and limitations of PDA, we pay special attention to its unique properties that specifically benefit biomedical microfluidic devices. We also discuss other potential applications of PDA beyond the current development. Through this review, we hope to promote PDA and encourage a broader adoption of PDA by the microfluidic community.

Simulation Analysis of Improving Microfluidic Heterogeneous Immunoassay Using Induced Charge Electroosmosis on a Floating Gate.

On-chip immuno-sensors are a hot topic in the microfluidic community, which is usually limited by slow diffusion-dominated transport of analytes in confined microchannels. Specifically, the antigen-antibody binding reaction at a functionalized area cannot be provided with enough antigen source near the reaction surface, since a small diffusion flux cannot match with the quick rate of surface reaction, which influences the response time and sensitivity of on-chip heterogeneous immunoassay. In this work, we propose a method to enhance the transportation of biomolecules to the surface of an antibody-immobilized electrode with induce charge electroosmotic (ICEO) convection in a low concentration suspension, so as to improve the binding efficiency of microfluidic heterogeneous immunoassays. The circular stirring fluid motion of ICEO on the surface of a floating gate electrode at the channel bottom accelerates the transport of freely suspended antigen towards the wall-immobilized antibodies. We investigate the dependence of binding efficiency on voltage magnitude and field frequency of the applied alternate current (AC) electrical field. The binding rate yields a factor of 5.4 higher binding for an applied voltage of 4 V at 10 Hz when the Damkohler number is 1000. The proposed microfluidic immuno-sensor technology of a simple electrode structure using ICEO convective fluid flow around floating conductors could offer exciting opportunities for diffusion-limited on-chip bio-microfluidic sensors.

Rapid Fabrication of Electrophoretic Microfluidic Devices from Polyester, Adhesives and Gold Leaf

In the last decade, the microfluidic community has witnessed an evolution in fabrication methodologies that deviate from using conventional glass and polymer-based materials. A leading example within this group is the print, cut and laminate (PCL) approach, which entails the laser cutting of microfluidic architecture into ink toner-laden polyester sheets, followed by the lamination of these layers for device assembly. Recent success when applying this method to human genetic fingerprinting has highlighted that it is now ripe for the refinements necessary to render it amenable to mass-manufacture. In this communication, we detail those modifications by identifying and implementing a suitable heat-sensitive adhesive (HSA) material to equip the devices with the durability and resilience required for commercialization and fieldwork. Importantly, this augmentation is achieved without sacrificing any of the characteristics which make the PCL approach attractive for prototyping. Exemplary HSA-devices performed DNA extraction, amplification and separation which, when combined, constitute the complete sequence necessary for human profiling and other DNA-based analyses.

Particle Migration due to Viscoelasticity of the Suspending Liquid and Its Relevance in Microfluidic Devices

The fast growth of microfluidic applications based on complex fluids is a result of the unique fluid dynamics of these systems, enabling the creation of devices for health care or biological and chemical analysis. Microchannels designed to focus, concentrate, or separate particles suspended in viscoelastic liquids are becoming common. The key fluid dynamical issue on which such devices work is viscoelasticity-induced lateral migration. This phenomenon was discovered in the 1960s in macroscopic channels and has received great attention within the microfluidic community in the past decade. This review presents the current understanding, both from experiments and theoretical analysis, of viscoelasticity-driven cross-flow migration. Examples of promising microfluidic applications show the unprecedented capabilities offered by such technology based on geometrically simple microchannels and rheologically complex liquids.

Novel prototyping method for microfluidic devices based on thermoplastic polyurethane microcapillary film

Thermoplastic polyurethane microcapillary film (TPU-MCF), as a novel extruded product, inherently contains an array of circular micron-sized capillaries embedded inside the polymer matrix. With the aid of simple laser cutting and conventional sealing technologies, a rapid prototyping method for microfluidic devices is proposed based on the ready-made microstructure of MCFs. Two functionalized microfluidic devices: serpentine micromixer and multi-droplet generator, are rapidly fabricated to demonstrate the advantages and potential of employing this new method. The whole proof-of-concept fabrication process can be completed in 8–10 min in a simple way; each procedure is repeatable with stable performance control of microfluidic devices; and the material cost can be as low as $0.01 for each device. The TPU-MCF and this novel method are expected to provide a new perspective and alternative in microfluidic community with particular requirements.

Fully-Programmable, Low-Cost, “Do-It-Yourself” Pressure Source for General Purpose Use in the Microfluidic Laboratory

Microfluidics is still a fast growing field and an interesting market, which increasingly demands sophisticated equipment and specific engineering solutions. Aside from the widely discussed chip technology, the external equipment and machinery to operate such a microfluidic chip system comes into focus. A number of companies offer solutions to pursue the various requests made by the microfluidic community. Commercially available systems for pumping fluids are versatile but also highly expensive. Here, we present a fully-programmable pressure source, which is low-cost and can be utilized for pressure-controlled fluid driving, destructive bonding tests, and other pressure-relevant experiments. We evaluated our setup and compared the performance to a commercially available system. Furthermore, we demonstrated the use of the system in the field of droplet microfluidics as a possible application. Our development aims to lower the entrance threshold for microfluidic technology and make it more accessible to a broader audience.

Role of standard documents in advancing the standardization of microfluidics connectors

An emerging trend within the microfluidic community is to standardize common parts in order to facilitate design and production activities. The goal is clear: to enhance interoperability and promote plug-and-play. A recent launch of a pan-European project, Microfluidic (MF) Manufacturing, has identified an item that is in immediate need of standardization: having in place geometrical specifications for MF connectors. In order to accelerate the adoption of such standards, there is a need to consider the pivotal role of standard documents. The purpose of this paper is to provide background information on document standards development. In addition, the future implications related to the MF manufacturing project will be discussed. A strengths, weaknesses, opportunities, and threats analysis has been carried out to identify points of action. The findings show that although there is a need to publish under International Organization for Standardization (ISO), the actual realization of a full ISO standard document is not feasible. The recommendation is to initially publish via an ISO Workshop Agreement. Parallel to such activity, there is a need to encourage stakeholders help kick start a currently dormant working group that supports microfluidics under ISO to help pave the way for future standardization activities in the microfluidics community.

Characterizing the Deformation of the Polydimethylsiloxane (PDMS) Membrane for Microfluidic System through Image Processing.

Polydimethylsiloxane (PDMS) membranes have been widely used in the microfluidic community to achieve various functions such as control, sensing, filter, etc. In this paper, an experimental process was proposed to directly characterize the deformation of the on-chip PDMS membrane at large deformation based on the image processing method. High precision pressures were applied on the surface of the PDMS membrane with fixed edges and a series deformation of the PDMS membrane were captured by the imaging system. The Chan and Vese (CV) level set method was applied to segment the images of the deformed membrane. The volumes wrapped by the deformed membranes were obtained, and pressure-volumes relationships of the PDMS membranes with different geometry parameters were also calculated. Then the membrane capacitance can be derived by differentiating the curve of pressure-volumes. In addition, the theoretical estimation of the capacitance of the PDMS membrane at large deformation was also obtained through finite element simulation (FEM), which was in good agreement with the experimental results. These results are expected to be significant for designing and on-chip measuring of such PDMS membrane based microfluidic components in our future work.

3D printing: an emerging tool for novel microfluidics and lab-on-a-chip applications

In the past few years, 3D printing technology has witnessed an explosive growth, penetrating various aspects of our lives. Current best-in-class 3D printers can fabricate micrometer scale objects, which has made fabrication of microfluidic devices possible. The highest achievable resolution is already at nanometer scale, which is continuing to drop. Since geometric complexity is not a concern for 3D printing, novel 3D microfluidics and lab-on-a-chip systems that are otherwise impossible to produce with traditional 2D microfabrication technology have started to emerge in recent years. In this review, we first introduce the basics of 3D printing technology for the microfluidic community and then summarize its emerging applications in creating novel microfluidic devices. We foresee widespread utilization of 3D printing for future developments in microfluidic engineering and lab-on-a-chip technology.

Induced-charge electrokinetics in a conducting nanochannel with broken geometric symmetry: Towards a flexible control of ionic transport

In the literature, conventional electrokinetics is widely used as a principle of operating nanofluidic devices. Different from the conventional electrokinetics involving nonpolarizable solid surfaces with fixed surface charge, induced-charge electrokinetic (ICEK) phenomena deal with polarizable surfaces with the ability of surface charge modulation through electric polarization under external electric fields. Because of several advantages, ICEK phenomena have drawn a great deal of attention in microfluidic community. Herein, we propose the first effort of extending the ICEK phenomena from microfluidics to nanofluidics. In particular, we report a numerical model for the ICEK phenomena in a tapered nanochannel with conducting (ideally polarizable) walls. It is shown that due to the broken geometric symmetry of the nanochannel, induced-charge electroosmotic flow inside the nanochannel exhibits a flow rectification such that electrolyte solution always flows from the narrow end of the nanochannel to the wide end for either a forward electric bias (electric field from the narrow to wide ends) or a reverse electric bias (electric field from the wide to narrow ends). In addition, we demonstrate that the ion selectivity of such tapered conducting nanochannel can be actively tuned to be cation-selective with a forward bias and anion-selective with a reverse bias. Promisingly, conducting nanochannels with broken geometric symmetry could be potentially used for constructing nanofluidic pumps with the unidirectional pumping capacity and ion selectors with the tuneable ionic selection.

Editorial: Moving on in biomicrofluidics.

Editorial: Moving on in biomicrofluidics.