Microfluidic Parts Research Articles

BIO27: Automated PDMS Engraving and Assembly of a Prototype Microfluidic Artificial Lung

Purpose: The ability to cost-effectively produce high-surface area microfluidic devices would bring many small-scale technologies from the realm of research to clinical and commercial applications. In particular microfluidic artificial lungs (µALs) promise improved gas exchange efficiency through micron-scale feature sizes. However, most µALs have only a single layer which limits their rated flows. Efforts to scale up these devices, such as by stacking multiple flat µALs have been labor intensive and resulted in bulky devices. Here, we present an automated roll-to-roll (R2R) manufacturing system and a cylindrical multi-layer µAL. Methods: The R2R system (Fig 1A) begins with a roll of biocompatible silicone rubber (Silpuran 2030). A heavily-modified CO2 laser engraver (Omtech K40 with custom vacuum engraving bed, N2 purge, and custom motherboard) creates patterns in the silicone sheet (Fig 1B). The sheet is then plasma-activated using two CeraPlas F-series cold-plasma wands to bond the PDMS to itself in an irreversible bond. Finally, it is rerolled into a processed device around a 30 mm PDMS core. This entire process from unrolling to rerolling is performed simultaneously and synchronously, allowing the creation of very large area microfluidic devices. Further, it is automated (Arduino Mega 1680), eliminating human error over this repetitive process. Results: Using our automated manufacturing system, we fabricated a 27-layer cylindrical prototype µAL, consisting of 1) an 8-layer base, 2) 11 layers of alternating blood and gas channels, and 3) an 8-layer protective cover. Laser-engraved fluidic channels were triangular, 60 µm deep and 180 µm wide (Fig 1B). If unrolled, the microfluidic part of this system would stretch 1.1 m, and the total length would stretch 2.7 m. This was placed into a custom 3D printed housing which routes blood and gas to their respective microfluidic channels (Fig 2A,B; filled with dyed water for visualization). Empirical pressure drop data were gathered for flows from 1 mL/min to 10 mL/min, which were similar to theoretical values (Fig 3). While the R2R manufacturing system successfully created the prototype 27-layer µAL, the device exhibited some internal fluid pooling and layer-to-layer leaks during fluidic testing. Both issues are believed to be caused by inadequate localized layer-to-layer adhesion. We plan to remedy these issues in the coming months. Conclusion: This roll-to-roll manufacturing system is designed to manufacture the first large surface-area microfluidic devices that are impractical to manufacture by conventional means. This can be employed for large-scale membrane gas exchange such as human-scale µALs.Figure 1. (A) An automated roll to roll manufacturing system for silicone. The path of the silicone is shown in green. The silicone comes on a protective PET backing, which is removed and highlighted in cyan. (B) Confocal scan of engraved Silpuran 2030. Channels were 60 µm deep, and 180 µm wide.Figure 2. (A) Finished device, with custom housing (B) Device with colored water being routed through. Red arrows depict blood connections, and blue arrows depict gas connections. Two of the blood outlets filled with blue dye, and there is a dark blue region indicating imperfect layer-to-layer bonding resulting in leaking.Figure 3. Experimental vs theoretical pressure drop across the μAL (water)

The Integration of Field Effect Transistors to Microfluidic Devices

Devices that integrate field effect transistors into microfluidic channels are becoming increasingly promising in the medical, environmental, and food realms, among other applications. The uniqueness of this type of sensor lies in its ability to reduce the background signals existing in the measurements, which interfere in obtaining good limits of detection for the target analyte. This and other advantages intensify the development of selective new sensors and biosensors with coupling configuration. This review work focused on the main advances in the fabrication and application of field effect transistors integrated into microfluidic devices as a way of identifying the potentialities that exist in these systems when used in chemical and biochemical analyses. The emergence of research on integrated sensors is not a recent study, although more recently the progress of these devices is more accentuated. Among the studies that used integrated sensors with electrical and microfluidic parts, those that investigated protein binding interactions seem to be the ones that expanded the most due, among other things, to the possibility of obtaining several physicochemical parameters involved in protein–protein interactions. Studies in this area have a great possibility of advancing innovations in sensors with electrical and microfluidic interfaces in new designs and applications.

Microfluidic Electrochemical Glucose Biosensor with In Situ Enzyme Immobilization

The development and characterization of a microfluidic electrochemical glucose biosensor are presented herein. The transducer part is based on thin-film metal electrodes on a glass substrate. The biological recognition element of the biosensor is the pyrroloquinoline quinone-glucose dehydrogenase (PQQ-GdhB) enzyme, selectively in situ immobilized via microcontact printing of a mixed self-assembling monolayer (SAM) on a gold working electrode, while the microfluidic part of the device comprises microchannel and microfluidic connections formed in a polydimethylsiloxane (PDMS) elastomer. The electrode properties throughout all steps of biosensor construction and the biosensor response to glucose concentration and analyte flow rate were characterized by cyclic voltammetry and chronoamperometry. A measurement range of up to 10 mM in glucose concentration with a linear range up to 200 μM was determined. A detection limit of 30 µM in glucose concentration was obtained. Respective biosensor sensitivities of 0.79 nA/µM/mm2 and 0.61 nA/µM/mm2 were estimated with and without a flow at 20 µL/min. The developed approach of in situ enzyme immobilization can find a wide number of applications in the development of microfluidic biosensors, offering a path towards continuous and time-independent detection.

Current and emerging trends in polymeric 3D printed microfluidic devices

During the last two decades, 3D printing technology has emerged as a valid alternative for producing microfluidic devices. 3D printing introduces new strategies to obtain high precision microfluidic parts without complex tooling and equipment, making the production of microfluidic devices cheaper, faster, and easier than conventional fabrication methods such as soft lithography. Among the main 3D techniques used for this purpose, fused filament manufacturing (FFF), inkjet 3D printing (i3Dp) and vat polymerization (VP) are of the greatest interest since they are well-established techniques in the field and are cost-affordable both in equipment and material. However, there are still some barriers in terms of technology and materials to overtake for definitively establishing 3D printing as a truly microfluidic production method. For example, the level of resolution and precision of 3D printed microfluidic parts still does not reach the level of conventional fabrication techniques, and, from a materialistic point of view, few materials present the desired characteristics (e.g., biocompatibility, optical transparency, and mechanical properties) for target areas such as medicine, analytical chemistry, and pharmaceuticals. This review intends to evaluate and analyze the current state of polymeric 3D printing techniques and materials to manufacture microfluidic chips. The article will show and discuss the latest innovations, materials, and applications of such 3D printed microstructures. The focus of this review is to provide an overview of recent and future developments in 3D printing and materials in the branch of microfluidics fabrications, showing that the selection of the right materials together with the design freedom afforded by 3D printing will be the cornerstone for microfluidic development.

Dynamic phase control with printing and fluidic materials' interaction by inkjet printing an RF sensor directly on a stereolithographic 3D printed microfluidic structure.

Stereolithographic (SL) three-dimensional (3D) printing of microfluidic channels and inkjet printing of radio frequency (RF) electronics are promising lab-on-a-chip technologies. However, the effective integration of the two techniques has been challenging since the fabricated parts need to be combined via an additional bonding process, such as plasma bonding. This study proposes combining RF electronics with SL printed microfluidic structures by directly inkjet printing onto a 3D printed mould. This allows the inkjet printing of RF electronics with high conductivity (8 × 106 S m-1) and high resolution (50 μm) as a surface modification of the 3D printed mould. This process combines the three-dimensional printing of microfluidic parts and the inkjet printing of RF sensors into a single process. The proposed approach increases the interaction between a printed RF part and a fluid material by adjusting the distance between them, and it can be applied to various resins and 3D printing methods. Furthermore, the proposed fabrication process was applied to a dynamic phase advanced and delayed transmission line (TL) operating at 3.8 GHz as a fluidic sensor. Consequently, using the same pattern, a higher phase shift range per microliter of 10° was obtained than the 1° for conventional phase shift TLs.

Особенности неразъемного клеевого соединения деталей микрофлюидных устройств из полиметилметакрилата

Особенности неразъемного клеевого соединения деталей микрофлюидных устройств из полиметилметакрилата

Tunable and Reversible Gelatin‐Based Bonding for Microfluidic Cell Culture

The development of novel bonding techniques could enable new applications and uses of plastics in microfluidic cell culture, complementing the omnipresent polydimethylsiloxane (PDMS). In this respect, the present paper describes a reversible gelatin‐based method (named GEL‐D) for bonding microfluidic chip parts, constituted of different materials. The herein introduced method enables the bonding of the most of the commonly used materials in microfluidics such as PMMA, PDMS, glass and NOA. Notably, the fabricated chips resist to pressure up to 0.7 MPa, to organic solvent exposure and temperature up to 70 °C. To show the versatility of the described method, microchips with different sizes, materials, and geometries were bonded, including microchannel down to 200 µm (width x depth) and round microstructures. The bonded chips are suitable to microfluidic cell culture procedures, including formation of microtissues, cells viability analysis and confocal microscopy. Therefore, the room‐temperature bonding method appear to be highly efficient for cell culture on plastic chips, where in situ analysis of the seeded cells is required after microchip de‐bonding.

Solvent-based bonding of PMMA–PMMA for microfluidic applications

Solvent bonding is a simple, inexpensive and quick technique used for joining microfluidic parts made of thermoplastic polymers that results in high bonding strength and good optical clarity. However, selecting the right solvent as well as the curing conditions is an important step in providing a successful bond that ensures an appropriate bonding without squeeze-out and clogging of microchannels. In this study, different solvent mixtures and solvent phases (i.e., liquid vs. vapor), as well as a range of curing times and temperatures, were tested to bond poly(methyl methacrylate) samples. Additionally, effect of corona surface modification was also examined on bonding quality. Results were compared in terms of bonding strength and optical clarity. A solvent mixture of 20% dichloromethane and 80% isopropanol showed the greatest bonding strength (4.2 MPa, based on tensile test), while vaporized dichloromethane had the best optical clarity (only 2.22% reduction in power transmittance). Coronal surface modification also showed a 25% increase in bonding strength and 2% improvement on optical clarity, for 20% dichloromethane and 80% isopropanol solution at room temperature and curing time of 15 min.

Design optimization of active microfluidic mixer incorporating micropillar on flexible membrane

In this paper, the optimization of a new design of active microfluidic mixer incorporating micropillar for accelerating the mixing of fluids was performed. The studied microfluidic mixer consists of the microfluidic, mechanical, and electromagnetic parts. The finite element analysis is used to study the effect of input channel angle, micropillar’s radius and spacing, and shape of membrane on the performance of mixer. In particular, the mixing flow rate, membrane deflection and micropillar swivel or bending were evaluated. The results show that the flow rate in the range of 3.78–3.88 µl/s which is almost two times of the input flow rate was obtained. The results also show that the deflection height ranging from 40 to 170 µm, micropillar swivel from 7° to 20° were obtained. Furthermore, from the comparison among the membrane shapes, it revealed that the membrane in circular shape generates higher deflection and swivel than the other membranes in square and rectangle shapes due to the uniform tensile stress distribution.

Batch fabrication of polymer microfluidic cartridges for QCM sensor packaging by direct bonding

Quartz crystal microbalance (QCM) sensing is an established technique commonly used in laboratory based life-science applications. However, the relatively complex, multi-part design and multi-step fabrication and assembly of state-of-the-art QCM cartridges make them unsuited for disposable applications such as point-of-care (PoC) diagnostics. In this work, we present the uncomplicated manufacturing of QCMs in polymer microfluidic cartridges. Our novel approach comprises two key innovations: the batch reaction injection molding of microfluidic parts; and the integration of the cartridge components by direct, unassisted bonding. We demonstrate molding of batches of 12 off-stoichiometry thiol-ene epoxy polymer (OSTE+) polymer parts in a single molding cycle using an adapted reaction injection molding process; and the direct bonding of the OSTE+ parts to other OSTE+ substrates, to printed circuit boards, and to QCMs. The microfluidic QCM OSTE+ cartridges were successfully evaluated in terms of liquid sealing as well as electrical properties, and the sensor performance characteristics are on par with those of a commercially available QCM biosensor cartridge. The simplified manufacturing of QCM sensors with maintained performance potentializes novel application areas, e.g. as disposable devices in a point of care setting. Moreover, our results can be extended to simplifying the fabrication of other microfluidic devices with multiple heterogeneously integrated components.

Tilted pillar array fabrication by the combination of proton beam writing and soft lithography for microfluidic cell capture Part 2: Image sequence analysis based evaluation and biological application.

As a continuation of our previously published work, this paper presents a detailed evaluation of a microfabricated cell capture device utilizing a doubly tilted micropillar array. The device was fabricated using a novel hybrid technology based on the combination of proton beam writing and conventional lithography techniques. Tilted pillars offer unique flow characteristics and support enhanced fluidic interaction for improved immunoaffinity based cell capture. The performance of the microdevice was evaluated by an image sequence analysis based in-house developed single-cell tracking system. Individual cell tracking allowed in-depth analysis of the cell-chip surface interaction mechanism from hydrodynamic point of view. Simulation results were validated by using the hybrid device and the optimized surface functionalization procedure. Finally, the cell capture capability of this new generation microdevice was demonstrated by efficiently arresting cells from a HT29 cell-line suspension.

Hybrid polymer composite membrane for an electromagnetic (EM) valveless micropump

In this paper, we report on a hybrid membrane used as an actuator in an electromagnetically driven valveless micropump developed using MEMS processes. The membrane structure consists of the combination of a magnetic polymer composite membrane and an attached bulk permanent magnet which is expected to have a compact structure and a strong magnetic force with maintained membrane flexibility. A soft polymeric material made of polydimethylsiloxane (PDMS) is initially mixed with neodymium magnetic particles (NdFeB) to form a magnetic polymer composite membrane. The membrane is then bonded with the PDMS based microfluidic part, developed using soft lithography process. The developed micropump was tested in terms of the actuator membrane deflection capability and the fluidic flow of the injected fluid sample through the microfluidic channel. The experimental results show that the magnetic composite actuator membrane with an attached bulk permanent magnet is capable of producing a maximum membrane deflection of up to 106 µm. The functionality test of the electromagnetic (EM) actuator for fluid pumping purposes was done by supplying an AC voltage with various amplitudes, signal waves and frequencies. A wide range of sample injection rates from a few µl min−1 to tens of nl min−1 was achieved with a maximum flow rate of 6.6 µl min−1. The injection flow rate of the EM micropump can be controlled by adjusting the voltage amplitude and frequency supplied to the EM coil, to control the membrane deflection in the pump chamber. The designed valveless EM micropump has a very high potential to enhance the drug delivery system capability in biomedical applications.

Low temperature co‐fired ceramics based modular fluidic system for efficient optical measurements

AbstractIn this paper some issues on development and functionality of the modular low temperature co‐fired ceramics (LTCC)‐based microfluidic system are discussed. Design, fabrication, and performance of an exemplary LTCC microfluidic system with separated electronic and microfluidic parts are presented. This microsystem utilizes absorbance and fluorescence measurement for determination of various chemical compounds in liquid test samples. According to performed measurements the analytical signal of the presented LTCC microfluidic system is characterized by good signal‐to‐noise ratio and repeatability.

Characteristic studies of a novel piezoelectric impedance micropump

This study reports the design, fabrication and test of an innovative valveless piezoelectric impedance micropump. The impedance micropump includes two nickel electroforming components, a stainless steel vibration plate, two glass tubes, a piezoelectric actuator and a glass substrate. A prototype of the micropump, with the dimensions of 16 mm × 9 mm × 1.0 mm, is made by precise manufacturing. The two plate nickel components were fabricated by multilevel electroforming technology on a stainless steel substrate. The top structure plate was electroformed by three-level structures, while the channel plate had a one-level structure. The vibration plate was manufactured by stainless steel through the lithography and etching process from MEMS fabrication technology. Holding a planar structure, the impedance micropump can be readily integrated with other microfluidic parts to form a lab-on-a-chip microdevice. The experimental results have demonstrated the liquid flow rate of 0.24 ml/min and the back pressure of 2.35 kPa, when the micropump was driven by the alternating sine-wave voltage of 200 Vpp at 18.4 kHz.

Tailored Chemical Surface Modifications of Different Types of Thermoplastic Materials for Microfluidic Applications

The high temperature of the melt during thermoplastic processing is utilized for the surface modification of thermoplastic parts. The approach is demonstrated for polycarbonate as a reactive polymer and polystyrene as a non‐reactive polymer. In case of polycarbonate, a polyamine is coupled to the polymer surface by chemical reaction. Functionalized latex beads are used for polystyrene, which are attached to the polymer surface by interdiffusion. Both surfaces adsorb selectively anionic or cationic dyes, respectively. The dyes are used as model compounds to demonstrate the potential of the surface modification approach for the fabrication of microfluidic parts. Those parts may be used for purification, accumulation, and reaction processes.

Direct assembly of cyclic olefin copolymer microfluidic devices helped by dry photoresist

A generic method for rapid, reproducible, and robust selective bonding of microfluidic chips made of Cyclic Olefin Copolymer (COC) has been developed and optimized. In this work we propose an adhesive bonding technique using ORDYL negative dry film photo-resist as glue to perform the packaging of COC micro-patterned structures. The ORDYL resist is qualified in terms of resolution, biocompatibility and fluidic sealing. The adhesive bonding is achieved by laminating a thin layer of ORDYL SY300 (<17μm) on top of the microfluidic part and then bonded to the other COC part. In this research, an oxygen plasma treatment for adhesion improvement was performed on COC surfaces at various plasma times. The bonding method is described in detail and the bonding quality of the chips was evaluated by a shear strength testing procedure and a leak test by pressurizing a microfluidic channel with an aqueous solution using an external peristaltic pump. Results are reported emphasizing the efficiency of the proposed approach and the developed process features high yields (>70%).

Automating microfluidic part verification

Microfluidic devices promise to significantly advance the field of medicine by providing diagnostic tools that may be administered at the point-of-care (POC). Currently, a major barrier to entry for POC microfluidic diagnostic technologies is part qualification where specific features of a microfluidic technology must be qualified during the manufacturing process to ensure the device performs properly, e.g., Tantra and van Heeren (Lab Chip 13:2199, 2013). Additionally, microfluidic device research is moving toward therapeutic applications where quality control requirements may be more stringent. In this paper, we use soft embossing—a replication technology—to manufacture high aspect ratio thermoplastic deterministic lateral displacement (DLD) parts, where DLD is a size-based microfluidic particle separation technology based on shift post arrays. Morphological data are collected using optical profilometry, and key metrics are automatically extracted using a novel image analysis algorithm. This algorithm allows us to rapidly quantify the average post height, post shape, array pitch and surface roughness in order to compare a lot of 12 devices to the original design and the deep reactive ion etched silicon master mold. During the run of 12 devices, the post height was 63.0 ± 5.1 μm (mean ± 6σ), the pitch was 35.6 ± 0.31 μm, the post eccentricity was 0.503 ± 0.197, the post circularity was 1.195 ± 0.084 and the root-mean-square surface roughness was 4.19 ± 3.39 μm. Importantly, this automated part qualification technique reduced data analysis time by 75- to 100-fold while allowing for additional qualification metrics and significantly reducing the need for manual measurement. Overall, this paper indicates that it is possible to improve the quality and efficiency of microfluidic part qualification using optical profilometry coupled with a novel image analysis algorithm.

Electromagnetic Valve Made in Low‐Temperature Co‐Fired Ceramics

This article describes the technology of the electromagnetic valve made in the LTCC (low temperature co‐fired ceramics). The actuation is supplied by mutual reaction between a 3D coil and a neodymium magnet bonded to flexible membrane. Such solution has many advantages like small power consumption and relatively great attractive forces. The valve is built in a hybrid polymer‐ceramic technology. The microfluidic and coil parts are fabricated in the LTCC technology. The flexible section is manufactured using a PDMS (poly(dimethylsiloxane)) membrane bonded to the ceramic part by plasma oxidation. The magnet is fixed on the membrane surface. The LTCC material was chosen for the sake of chemical durability and possibility of 3D structuration. The PDMS membrane provides simultaneously very good stability and high flexibility.

Integration of multiple components in polystyrene-based microfluidic devices part II: cellular analysis

In Part II of this series describing the use of polystyrene (PS) devices for microfluidic-based cellular assays: various cellular types and detection strategies are employed to determine three fundamental assays often associated with cells. Specifically, using either integrated electrochemical sensing or optical measurements with a standard multi-well plate reader, cellular uptake, production, or release of important cellular analytes are determined on a PS-based device. One experiment involved the fluorescence measurement of nitric oxide (NO) produced within an endothelial cell line following stimulation with ATP. The result was a four-fold increase in NO production (as compared to a control), with this receptor-based mechanism of NO production verifying the maintenance of cell receptors following immobilization onto the PS substrate. The ability to monitor cellular uptake was also demonstrated by optical determination of Ca(2+) into endothelial cells following stimulation with the Ca(2+) ionophore A20317. The result was a significant increase (42%) in the calcium uptake in the presence of the ionophore, as compared to a control (17%) (p < 0.05). Finally, the release of catecholamines from a dopaminergic cell line (PC 12 cells) was electrochemically monitored, with the electrodes being embedded into the PS-based device. The PC 12 cells had better adherence on the PS devices, as compared to use of PDMS. Potassium-stimulation resulted in the release of 114 ± 11 μM catecholamines, a significant increase (p < 0.05) over the release from cells that had been exposed to an inhibitor (reserpine, 20 ± 2 μM of catecholamines). The ability to successfully measure multiple analytes, generated in different means from various cells under investigation, suggests that PS may be a useful material for microfluidic device fabrication, especially considering the enhanced cell adhesion to PS, its enhanced rigidity/amenability to automation, and its ability to enable a wider range of analytes to be investigated, even analytes with a high degree of hydrophobicity.

Feedback/feedforward modeling and control of electroosmotic flow in a T-shape microchannel

Electroosmotic effect is usually utilized to generate the flow field in microfluidic systems. In many of these microdevices, an accurate control over the output flow rate of the microfluidic part is necessary for the successful operation of the whole system. In this study, a combined feedback/feedforward strategy is proposed to control the output flow rate in a micro-T-junction. First, finite element model of the electroosmotic flow in the T-junction is generated; second, using the adaptive neural fuzzy inference system, the finite element model forms a basis for generating training data for building an inverse model of the flow in the micro-T-junction. This inverse model serves as a controller in the feedforward part of the system. Then, in order to make the controller robust against disturbances and uncertainties such as dimensional tolerances, a Mamdani-type fuzzy logic controller is incorporated in the feedback part of the controller. Finally, simulation results are presented in order to proof the performance of the designed controller.