Modular Microfluidic Device Research Articles

A modular microfluidic device that uses magnetically actuatable microposts for enhanced magnetic bead-based workflows.

Magnetic beads have been widely and successfully used for target enrichment in life science assays. There exists a large variety of commercially available magnetic beads functionalized for specific target capture, as well as options that enable simple surface modifications for custom applications. While magnetic beads are ideal for use in the macrofluidic context of typical laboratory workflows, their performance drops in microfluidic contexts, such as consumables for point-of-care diagnostics. A primary cause is the diffusion-limited analyte transport in these low Reynolds number environments. A new method, BeadPak, uses magnetically actuatable microposts to enhance analyte transport, improving yield of the desired targets. Critical parameters were defined for the operation of this technology and its performance characterized in canonical life-science assays. BeadPak achieved up to 1000× faster capture than a microfluidic chamber relying on diffusion alone, enabled a significant specimen concentration via volume reduction, and demonstrated compatibility with a range of biological specimens. The results shown in this work can be extended to other systems that utilize magnetic beads for target capture, concentration, and/or purification.

Microfluidic Chromatography for Enhanced Amino Acid Detection at Ocean Worlds.

Increasing interest in the detection of biogenic signatures, such as amino acids, on icy moons and bodies within our solar system has led to the development of compact in situ instruments. Given the expected dilute biosignatures and high salinities of these extreme environments, purification of icy samples before analysis enables increased detection sensitivity. Herein, we outline a novel compact cation exchange method to desalinate proteinogenic amino acids in solution, independent of the type and concentration of salts in the sample. Using a modular microfluidic device, initial experiments explored operational limits of binding capacity with phenylalanine and three model cations, Na+, Mg2+, and Ca2+. Phenylalanine recovery (94–17%) with reduced conductivity (30–200 times) was seen at high salt-to-amino-acid ratios between 25:1 and 500:1. Later experiments tested competition between mixtures of 17 amino acids and other chemistries present in a terrestrial ocean sample. Recoveries ranged from 11% to 85% depending on side chain chemistry and cation competition, with concentration shown for select high affinity amino acids. This work outlines a nondestructive amino acid purification device capable of coupling to multiple downstream analytical techniques for improved characterization of icy samples at remote ocean worlds.

Flow Chemistry: A Sustainable Voyage Through the Chemical Universe en Route to Smart Manufacturing.

Microfluidic devices and systems have entered many areas of chemical engineering, and the rate of their adoption is only increasing. As we approach and adapt to the critical global challenges we face in the near future, it is important to consider the capabilities of flow chemistry and its applications in next-generation technologies for sustainability, energy production, and tailor-made specialty chemicals. We present the introduction of microfluidics into the fundamental unit operations of chemical engineering. We discuss the traits and advantages of microfluidic approaches to different reactive systems, both well-established and emerging, with a focus on the integration of modular microfluidic devices into high-efficiency experimental platforms for accelerated process optimization and intensified continuous manufacturing. Finally, we discuss the current state and new horizons in self-driven experimentation in flow chemistry for both intelligent exploration through the chemical universe and distributed manufacturing.

Self‐sealing thermoplastic fluoroelastomer enables rapid fabrication of modular microreactors

AbstractA novel fluorinated soft thermoplastic elastomer (sTPE) for microfluidics is presented. It allows the rapid fabrication of microfluidic devices through a 30‐second hot embossing cycle at 220°C followed by self‐sealing through simple conformal contact at room temperature, or with baking. The material shows high chemical resistance, particularly in comparison to polydimethylsiloxane (PDMS), to many common organic solvents and can be rapidly micropatterned with high fidelity using a variety of microfluidic master molds thanks to its low mechanical stiffness. Self‐sealing of the material is reversible and withstands pressures of up to 2.8 bar with room temperature sealing and four bar with baking at 185°C for 2 hours. The elastomeric, transparent sTPE exhibits material characteristics that make it suited for use as a microreactor, such as low absorption, surface roughness and oxygen permeability, while also allowing a facile and scalable fabrication process. Modular microfluidic devices, leveraging the fast and reversible room temperature self‐sealing, are demonstrated for the generation of water droplets in a toluene continuous phase using T‐junctions of variable size. The sTPE offers an alternative to common microfluidic materials, overcoming some of their key drawbacks, and giving scope for low‐cost and high‐throughput devices for flow chemistry applications.

Modular microfluidics enables kinetic insight from time-resolved cryo-EM

Mechanistic understanding of biochemical reactions requires structural and kinetic characterization of the underlying chemical processes. However, no single experimental technique can provide this information in a broadly applicable manner and thus structural studies of static macromolecules are often complemented by biophysical analysis. Moreover, the common strategy of utilizing mutants or crosslinking probes to stabilize intermediates is prone to trapping off-pathway artefacts and precludes determining the order of molecular events. Here we report a time-resolved sample preparation method for cryo-electron microscopy (trEM) using a modular microfluidic device, featuring a 3D-mixing unit and variable delay lines that enables automated, fast, and blot-free sample vitrification. This approach not only preserves high-resolution structural detail but also substantially improves sample integrity and protein distribution across the vitreous ice. We validate the method by visualising reaction intermediates of early RecA filament growth across three orders of magnitude on sub-second timescales. The trEM method reported here is versatile, reproducible, and readily adaptable to a broad spectrum of fundamental questions in biology.

3D-Printed Modular Microfluidic Device Enabling Preconcentrating Bacteria and Purifying Bacterial DNA in Blood for Improving the Sensitivity of Molecular Diagnostics.

Molecular diagnostics for sepsis is still a challenge due to the presence of compounds that interfere with gene amplification and bacteria at concentrations lower than the limit of detection (LOD). Here, we report on the development of a 3D printed modular microfluidic device (3DpmμFD) that preconcentrates bacteria of interest in whole blood and purifies their genomic DNA (gDNA). It is composed of a W-shaped microchannel and a conical microchamber. Bacteria of interest are magnetically captured from blood in the device with antibody conjugated magnetic nanoparticles (Ab-MNPs) at 5 mL/min in the W-shaped microchannel, while purified gDNA of the preconcentrated bacteria is obtained with magnetic silica beads (MSBs) at 2 mL/min in the conical microchamber. The conical microchamber was designed to be connected to the microchannel after the capturing process using a 3D-printed rotary valve to minimize the exposure of the MSBs to interfering compounds in blood. The pretreatment process of spiked blood (2.5 mL) can be effectively completed within about 50 min. With the 3DpmμFD, the LOD for the target microorganism Escherichia coli O157:H7 measured by both polymerase chain reaction (PCR) with electrophoresis and quantitative PCR was 10 colony forming unit (CFU) per mL of whole blood. The results suggest that our method lowers the LOD of molecular diagnostics for pathogens in blood by providing bacterial gDNA at high purity and concentration.

Reusable Standardized Universal Interface Module (RSUIM) for Generic Organ-on-a-Chip Applications.

The modular-based multi-organ-on-a-chip enables more stable and flexible configuration to better mimic the complex biological phenomena for versatile biomedical applications. However, the existing magnetic-based interconnection modes are mainly realized by directly embedding and/or fixing magnets into the modular microfluidic devices for single use only, which will inevitably increase the complexity and cost during the manufacturing process. Here, we present a novel design of a reusable standardized universal interface module (RSUIM), which is highly suitable for generic organ-on-chip applications and their integration into multi-organ systems. Both pasting-based and clamping-based interconnection modes are developed in a plug-and-play manner without fluidic leakage. Furthermore, due to the flexibility of the modular design, it is simple to integrate multiple assembled modular devices through parallel configuration into a high throughput platform. To test its effectiveness, experiments on the construction of both the microvascular network and vascularized tumor model are performed by using the integration of the generic vascularized organ-on-a-chip module and pasting-based RSUIM, and their quantitative analysis results on the reproducibility and anti-cancer drug screening validation are further performed. We believe that this RSUIM design will become a standard and critical accessory for a broad range of organ-on-a-chip applications and is easy for commercialization with low cost.

Microfluidic Modules with Integrated Solid-State Sensors for Reconfigurable Miniaturized Analysis Systems

The fast and simple fabrication of modular microfluidic devices comprising different fluidic components and configurations that can rapidly be assembled and reconfigured depending on the requirements of a particular application is very attractive. The application of these modular systems as complete analysis systems requires the incorporation of flow-cell modules capable of selectively detecting chemical species. Here, a new magnetic clamping approach is presented that allows both interconnection of microfluidic modules and reversible integration of solid-state sensors. Planar and optically transparent materials are used to easily assess device fluidic performance. Double-sided polyacrylic adhesive layers, sandwiched between two transparent polycarbonate films, are mechanized to produce fluidic structures containing the required inlets and outlets. The latter also include chemically bonded poly(dimethylsiloxane) gaskets for easy leak-free interconnection of the different modules and the incorporation of c...

A hybrid modular microfluidic device for emulsion generation

We report a novel modular plug-and-play microfluidic device for versatile emulsion generation, which consists of three parts: a top module for the dispersed phase supply, a glass capillary for emulsion creation and a bottom module for the continuous phase supply. By combining different modules and tapered glass capillaries, single emulsions, Janus emulsions and double emulsions have been successfully produced. The hybrid strategy allows us to produce smaller droplets through the tapered glass nozzles compared to current fully 3D-printed devices. On the other hand, it provides a simple and plug-and-play assembly manner compared to conventional microfluidic devices. Screw-thread plus gasket strategy has been proved to successfully seal the device and separate different liquid phases. Finally, magnetically responsive microparticles are synthesized based on the droplet templates produced in our device, which can be potentially applied in sensor and actuator fields.

A Modular Microfluidic Device via Multimaterial 3D Printing for Emulsion Generation

3D-printing (3DP) technology has been developing rapidly. However, limited studies on the contribution of 3DP technology, especially multimaterial 3DP technology, to droplet-microfluidics have been reported. In this paper, multimaterial 3D-printed devices for the pneumatic control of emulsion generation have been reported. A 3D coaxial flexible channel with other rigid structures has been designed and printed monolithically. Numerical and experimental studies have demonstrated that this flexible channel can be excited by the air pressure and then deform in a controllable way, which can provide the active control of droplet generation. Furthermore, a novel modular microfluidic device for double emulsion generation has been designed and fabricated, which consists of three modules: function module, T-junction module, and co-flow module. The function module can be replaced by (1) Single-inlet module, (2) Pneumatic Control Unit (PCU) module and (3) Dual-inlet module. Different modules can be easily assembled for different double emulsion production. By using the PCU module, double emulsions with different number of inner droplets have been successfully produced without complicated operation of flow rates of different phases. By using single and dual inlet module, various double emulsions with different number of encapsulated droplets or encapsulated droplets with different compositions have been successfully produced, respectively.

3D printed Lego®-like modular microfluidic devices based on capillary driving

The field of how to rapidly assemble microfluidics with modular components continuously attracts researchers’ attention, however, extra efforts must be devoted to solving the problems of leaking and aligning between individual modules. This paper presents a novel type of modular microfluidic device, driven by capillary force. There is no necessity for a strict seal or special alignment, and its open structures make it easy to integrate various stents and reactants. The key rationale for this method is to print different functional modules with a low-cost three-dimensional (3D) printer, then fill the channels with capillary materials and assemble them with plugs like Lego® bricks. This rapidly reconstructed modular microfluidic device consists of a variety of common functional modules and other personalized modules, each module having a unified standard interface for easy assembly. As it can be printed by a desktop 3D printer, the manufacturing process is simple and efficient, with controllable regulation of the flow channel scale. Through diverse combinations of different modules, a variety of different functions can be achieved, without duplicating the manufacturing process. A single module can also be taken out for testing and analysis. What’s more, combined with basic circuit components, it can serve as a low-cost Lego®-like modular microfluidic circuits. As a proof of concept, the modular microfluidic device has been successfully demonstrated and used for stent degradation and cell cultures, revealing the potential use of this method in both chemical and biological research.

Characterization of an encapsulated insulin secreting human pancreatic beta cell line in a modular microfluidic device

Type I diabetes mellitus is characterised by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments. We have developed and characterised different alginate-poly-l-lysine-alginate (APA) microcapsules loaded with the insulin producing 1.1B4 cell line. Static in vitro studies confirmed a constant insulin secretion and a boost of the secretion when the medium was enriched with glucose. Nevertheless, these results were not completely reproduced in a dynamic system by APA liquefied microcapsules containing 1.1B4 cells. The dynamic culture setting created by a microfluidic device, allowed the determination of the glucose response in APA liquefied microcapsules, showing that dynamic conditions can mimic better physiological in vivo environments.

Microfluidic Diffusion Viscometer for Rapid Analysis of Complex Solutions.

The viscosity of complex solutions is a physical property of central relevance for a large number of applications in material, biological, and biotechnological sciences. Here we demonstrate a microfluidic technology to measure the viscosity of solutions by following the advection and diffusion of tracer particles under steady-state flow. We validate our method with standard water-glycerol mixtures, and then we apply this microfluidic diffusion viscometer to measure the viscosity of protein solutions at high concentrations as well as of a crude cell lysate. Our approach exhibits a series of attractive features, including analysis time on the order of seconds and the consumption of a few μL of sample, as well as the possibility to readily integrate the microfluidic viscometer in other instrument platforms or modular microfluidic devices. These characteristics make microfluidic diffusion viscometry an attractive approach in automated processes in biotechnology and health-care sciences where fast measurements with limited amount of sample consumption are required.

Polydimethylsiloxane Connection for Quartz Microchips in a High-Pressure System

An interconnecting technique, the "PDMS connection method", for quartz microchips in a high-pressure system is presented. The connection between quartz microchips is an essential technology for modular microfluidic devices, such as microchip-HPLC. PDMS was applied to the seal material, being spread on the seal side of the chips, and set into the metal housing. The characteristics of the PDMS connection method concerning pressure resistance and the extension of the peak were examined. The experimental results showed a good seal at 5 MPa, which seem to be sufficient for realizing microchip-HPLC utilizing a monolithic silica capillary column as a separation medium. The influence of the extra column effect on chromatographic separation was almost the same as in the case using a commercial union fitting. In addition, the PDMS connection enabled the detachability of chip-based modules with user-friendliness. Our experimental findings suggest that the novel PDMS connection method can possibly be applied as a generic technology in high-pressure microTAS.