Microfluidic Fluid Research Articles

Printed and Laser Induced Graphene Electrochemical Biosensors for Rapid Environmental and Biomedical Monitoring

This presentation will demonstrate how low-cost printed and flexible graphene circuits can overcome the challenges associated with conventional electrical circuits to open the door to a highly sensitive monitoring of biochemical threats and toxins including nerve agents/pesticides. The use of inkjet and aerosol printing; spin coating; and laser writing (i.e., laser induced graphene) can be used to create such circuits with high resolution (line widths as low as 20 µm). Moreover, the use of rapid-pulse laser annealing of the printed graphene and/or salt porogens added into graphene inks before printing can be used to further improve the electrical conductivity (< 10 ohms/sq.) and electroactive surface area (nano/micro structuring) of the graphene circuits as well as be used to tune the surface of the printed graphene from one that is hydrophilic (water contact angle (WCA) = 48°) to one that is superhydrophobic (WCA = 158°). More recently we demonstrate how graphene synthesis, patterning and surface wettability can all be controlled through a laser induced graphene (LIG) process that creates a high surface area graphene surface directly from polyimide. Such LIG circumvents the need to create solution-phase graphene inks for printing. These printing and laser fabrication techniques are also amenable for use on flexible and chemically/thermally sensitive surfaces including polymers and paper.Moreover, the laser etched printed graphene and LIG exhibits an inherent 3D morphology that significantly increases the electrode electroactive surface over traditional 2D planar graphene electrodes. This large increase in surface area significantly improves the loading of enzyme onto the electrode surface and subsequently increases the heterogenous charge transport during catalytic pesticide sensing. Such ion sensors displayed near-Nernstian sensitivities, wide sensing ranges over four orders of magnitude extending from the 10–2 M down to detection limits in the 10–6 M range or for fertilizer ions (nitrate, ammonium, potassium, calcium, and magnesium) reaching down to detection limits less than 1 ppm in some cases in soil and water samples. The pesticide sensing capability of the sensor is able to reach an extremely low picomolar detect limit for organophosphates (paraoxon) and to the nanomolar regime for neonicotinoids in surface waters. We also demonstrate how this flexible LIG electrodes can be coupled with polymeric microfluidics and adhered to the body for continuous monitoring of lactate, glucose, and sodium in the sweat. Finally, we demonstrate how such surface wettability patterning of the printed graphene and LIG itself through laser etching can be used to make hydrophilic LIG tracks surrounded by near superhydrophic sidewalls for open microfluidic fluid transport without the need for polymeric microfluidics. Such open microfluidic tracks enable the splitting and transport of fluid samples to distinct electrochemical sensors for multiplexed biosensing of both fertilizer ion and pesticide monitoring from water samples and assist in harvesting sprayed pesticides in the field. Figure 1

Influence of Non-Newtonian Viscosity on Flow Structures and Wall Deformation in Compliant Serpentine Microchannels: A Numerical Study.

The viscosity of fluid plays a major role in the flow dynamics of microchannels. Viscous drag and shear forces are the primary tractions for microfluidic fluid flow. Capillary blood vessels with a few microns diameter are impacted by the rheology of blood flowing through their conduits. Hence, regenerated capillaries should be able to withstand such impacts. Consequently, there is a need to understand the flow physics of culture media through the lumen of the substrate as it is one of the vital promoting factors for vasculogenesis under optimal shear conditions at the endothelial lining of the regenerated vessel. Simultaneously, considering the diffusive role of capillaries for ion exchange with the surrounding tissue, capillaries have been found to reorient themselves in serpentine form for modulating the flow conditions while developing sustainable shear stress. In the current study, S-shaped (S1) and delta-shaped (S2) serpentine models of capillaries were considered to evaluate the shear stress distribution and the oscillatory shear index (OSI) and relative residual time (RRT) of the derivatives throughout the channel (due to the phenomena of near-wall stress fluctuation), along with the influence of culture media rheology on wall stress parameters. The non-Newtonian power-law formulation was implemented for defining rheological viscosity of the culture media. The flow actuation of the media was considered to be sinusoidal and physiological, realizing the pulsatile blood flow behavior in the circulatory network. A distinct difference in shear stress distributions was observed in both the serpentine models. The S1 model showed higher change in shear stress in comparison to the S2 model. Furthermore, the non-Newtonian viscosity formulation was found to produce more sustainable shear stress near the serpentine walls compared to the Newtonian formulation fluid, emphasizing the influence of rheology on stress generation. Further, cell viability improved in the bending regions of serpentine channels compared to the long run section of the same channel.

Effect of wall slip on the viscoelastic particle ordering in a microfluidic channel.

The formation of a line of equally spaced particles at the centerline of a microchannel, referred as "particle ordering," is desired in several microfluidic applications. Recent experiments and simulations highlighted the capability of viscoelastic fluids to form a row of particles characterized by a preferential spacing. When dealing with non-Newtonian fluids in microfluidics, the adherence condition of the liquid at the channel wall may be violated and the liquid can slip over the surface, possibly affecting the orderingefficiency. In this work, we investigate the effect of wall slip on the ordering of particles suspended in a viscoelastic liquid by numerical simulations. The dynamics of a triplet of particles in an infinite cylindrical channel is first addressed by solving the fluid and particle governing equations. The relative velocities computed for the three-particle system are used to predict the dynamics of a train of particles flowing in a long microchannel. The distributions of the interparticle spacing evaluated at different slip coefficients, linear particle concentrations, and distances from the channel inlet show that wall slip slows down the self-assembly mechanism. For strong slipping surfaces, no significant change of the initial microstructure is observed at low particle concentrations, whereas strings of particles in contact form at higher concentrations. The detrimental effect of wall slip on viscoelastic ordering suggests care when designing microdevices, especially in case of hydrophobic surfaces that may enhance the slippingphenomenon.

Microfluidic T Cell Selection by Cellular Avidity.

No T cell receptor (TCR) T cell therapies have obtained clinical approval. The lack of strategies capable of selecting and recovering potent T cell candidates may be a contributor to this. Existing protocols for selecting TCR T cell clones for cell therapies such as peptide multimer methods have provided effective measurements on TCR affinities. However, these methods lack the ability to measure the collective strength of intercellular interactions (i.e., cellular avidity) and markers of T cell activation such as immunological synapse formation. This study describes a novel microfluidic fluid shear stress-based approach to identify and recover highly potent T cell clones based on the cellular avidity between living T cells and tumor cells. This approach is capable of probing approximately up to 10000 T cell-tumor cell interactions per run and can recover potent T cells with up to 100% purity from mixed populations of T cells within 30 min. Markers of cytotoxicity, activation, and avidity persist when recovered high cellular avidity T cells are subsequently exposed to fresh tumor cells. These results demonstrate how microfluidic probing of cellular avidity may fast track the therapeutic T cell selection process and move the authors closer to precision cancer immunotherapy.

Past, Present, and Future of Microfluidic Fluid Analysis in the Energy Industry

Past, Present, and Future of Microfluidic Fluid Analysis in the Energy Industry

A simple acoustofluidic device for on-chip fabrication of PLGA nanoparticles.

Miniaturization of systems and processes provides numerous benefits in terms of cost, reproducibility, precision, minimized consumption of chemical reagents, and prevention of contamination. The field of microfluidics successfully finds a place in a plethora of applications, including on-chip nanoparticle synthesis. Compared with the bulk approaches, on-chip methods that are enabled by microfluidic devices offer better control of size and uniformity of fabricated nanoparticles. However, these microfluidic devices generally require complex and expensive fabrication facilities that are not readily available in low-resourced laboratories. Here, a low-cost and simple acoustic device is demonstrated by generating acoustic streaming flows inside glass capillaries through exciting different flexural modes. At distinct frequencies, the flexural modes of the capillary result in different oscillation profiles that can insert harmonic forcing into the fluid. We explored these flexural modes and identified the modes that can generate strong acoustic streaming vortices along the glass capillary. Then, we applied these modes for fluid mixing using an easy-to-fabricate acoustofluidic device architecture. This device is applied in the fabrication of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles. The acoustic device consists of a thin glass capillary and two polydimethylsiloxane adaptors that are formed using three-dimensional printed molds. By controlling the flow rates of the polymer and water solutions, PLGA nanoparticles with diameters between 65 and 96 nm are achieved with polydispersity index values ranging between 0.08 and 0.18. Owing to its simple design and minimal fabrication requirements, the proposed acoustofluidic mixer can be applied for microfluidic fluid mixing applications in limited resource settings.

Performance optimization of a novel passive T-shaped micromixer with deformable baffles

Micromixers are critical components within microfluidic fluid handling and analysis systems. When it comes to micromixing of biological samples, the hydrodynamical forces acting on biological specimens are of great importance besides mixing quality. Although adding rigid obstacles to the microchannels has shown to improve the mixing performance, they create a considerable pressure drop and impose a significant shear force on biological specimens. To address these problems, deformable baffles have been introduced here as a novel tuning tool for controlling the mixing characteristics. To optimize the device performance (maximizing the mixing performance and minimizing the pressure loss), two optimization algorithms have been employed to find out the suitable baffle geometry and material property. The Taguchi method was proposed as a fast and cost-effective approach for single-objective optimization of the mixing index or the pressure drop, and the Pareto optimality concept was introduced for parallel optimization of the mixing efficiency and the pressure loss. The results show that replacing the rigid with deformable baffles significantly reduces the pressure drop (by approximately 50%), causing a significant reduction in the shear stress on biological samples while a small reduction on the mixing efficiency (10 to 15%) was observed.

Advances in Nanoliposomes Production for Ferrous Sulfate Delivery.

In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization.

Adhesive wafer bonding for CMOS based lab-on-a-chip devices

Adhesive wafer bonding using laminated photosensitive dry-resist offers many advantages and can be used to realize advanced, CMOS integrated, lab-on-a-chip devices. The low bond-temperatures involved allow the hybrid integration of a range of substrates, e.g. CMOS wafers with structured MEMS glass wafers. The dry-film polymer functions as an adhesive interlayer and can be lithographically patterned to form sealed microfluidic fluid channels and chambers. This approach is well suited for low-cost R&D prototyping, and efforts reported in the past were often limited to proof-of-concept devices. However, all of the involved process steps do have the potential to be scaled up for an industrial volume production. We report on our activities to implement a baseline 8″ process flow, using the ORDYL SY300 series of permanent dry-film resist, to enable the commercial manufacturing of microfluidic devices based on this technology at a MEMS foundry. Advantages and disadvantages of the presented approach are discussed.

Shaping and transporting diamagnetic sessile drops.

Electromagnetic fields are commonly used to control small quantities of fluids in microfluidics and digital microfluidics. Magnetic control techniques are less well studied than their electric counterparts, with only a few investigations into liquid diamagnetism. The ratio of magnetic to surface energy (magnetic Bond number ) is an order of magnitude smaller for diamagnetic drops ( at 1.2 T applied field) than for paramagnetic drops ( at 1.2 T applied field). This weaker interaction between the magnetic field and the diamagnetic drop has led to the phenomenon being overlooked in digital microfluidics. Here, we investigate shaping and transport of diamagnetic drops using magnetostatic fields. Our findings highlight how diamagnetic fluids can be used as a novel tool in the toolbox of microfluidics and digital microfluidics.

Cassie-Baxter Surfaces for Reversible, Barrier-Free Integration of Microfluidics and 3D Cell Culture.

3D cell culture and microfluidics both represent powerful tools for replicating critical components of the cell microenvironment; however, challenges involved in the integration of the two and compatibility with standard tissue culture protocols still represent a steep barrier to widespread adoption. Here we demonstrate the use of engineered surface roughness in the form of microfluidic channels to integrate 3D cell-laden hydrogels and microfluidic fluid delivery. When a liquid hydrogel precursor solution is pipetted onto a surface containing open microfluidic channels, the solid/liquid/air interface becomes pinned at sharp edges such that the hydrogel forms the "fourth wall" of the channels upon solidification. We designed Cassie-Baxter microfluidic surfaces that leverage this phenomenon, making it possible to have barrier-free diffusion between the channels and the hydrogel; in addition, sealing is robust enough to prevent leakage between the two components during fluid flow, but the sealing can also be reversed to facilitate recovery of the cell/hydrogel material after culture. This method was used to culture MDA-MB-231 cells in collagen, which remained viable and proliferated while receiving media exclusively through the microfluidic channels over the course of several days.

An integrated and automated electronic system for point-of-care protein testing.

Protein testing in blood is important for clinical analysis. Traditional blood tests are performed in centralized laboratories and are slow to provide results. In contrast, point-of-care devices deliver rapid results in non-laboratory settings, allowing timely analysis and in turn reducing healthcare costs. Successful point-of-care platforms require seamless integration of chemical assays, fluid management and signal readout. In this regard, we present an integrated, compact and automated electronic system for point-of-care protein sensing. The system comprises of a microfluidics-based electrochemical biosensor, amperometry circuitry and automated microfluidic fluid handling circuitry. This platform utilizes magnetic microbeads to expedite an electronic enzyme-linked immunosorbent assay, and microfluidics to manage small volumes and automate assay operations. A commercial single-chip potentiostat is utilized for amperometry measurements and microfluidics control. Using this all-electrical system, we demonstrate an integrated and automated assay for human interleukin-6.

Flowing and pressurizing a solid-liquid two phase monodispersed fluid with high solid content in a transparent microfluidic high-pressure chip

Handling highly concentrated solid-liquid two-phase fluids in microfluidics is challenging. In this paper, we present the first studies of flowing solder paste with a high solid content in a transparent high-pressure tolerant glass chip, thereby increasing the understanding of how multiphase liquids with high density difference between the phases behave in small channels (840 µm in diameter). The system, including a custom made high-pressure, low resistance, interface, was continuously operated at pressures up to of 6 MPa and devices where shown to have pressure tolerance up to 17 MPa. During flow through the chip, the packing density of the solder balls displayed inhomogeneity over the channel where chains of solder balls in contact with each other were formed together with voids. These in-homogeneities persisted along the channel during flow. The flow rate of the paste through the chip oscillated between 63 to 350 µm/s when pumping at constant volume rate of 30 µl/min. When a pressure of 2 MPa was applied, the volume of the solder paste particle segment decreased 1.6%, and 0.1% was elastically recovered when the pressure was released. It is concluded that this transparent microfluidic high-pressure glass chip with the special developed interface is suitable for flow studies of solder paste with a high solid content.

Численное моделирование процессов тепломассопереноса в микрофлюидном тепловом датчике потока

Численное моделирование процессов тепломассопереноса в микрофлюидном тепловом датчике потока

Microfluidic Mixing and Analog On-Chip Concentration Control Using Fluidic Dielectrophoresis.

Microfluidic platforms capable of complex on-chip processing and liquid handling enable a wide variety of sensing, cellular, and material-related applications across a spectrum of disciplines in engineering and biology. However, there is a general lack of available active microscale mixing methods capable of dynamically controlling on-chip solute concentrations in real-time. Hence, multiple microfluidic fluid handling steps are often needed for applications that require buffers at varying on-chip concentrations. Here, we present a novel electrokinetic method for actively mixing laminar fluids and controlling on-chip concentrations in microfluidic channels using fluidic dielectrophoresis. Using a microfluidic channel junction, we co-flow three electrolyte streams side-by-side so that two outer conductive streams enclose a low conductive central stream. The tri-laminar flow is driven through an array of electrodes where the outer streams are electrokinetically deflected and forced to mix with the central flow field. This newly mixed central flow is then sent continuously downstream to serve as a concentration boundary condition for a microfluidic gradient chamber. We demonstrate that by actively mixing the upstream fluids, a variable concentration gradient can be formed dynamically downstream with single a fixed inlet concentration. This novel mixing approach offers a useful method for producing variable on-chip concentrations from a single inlet source.

Flexible optofluidic waveguide platform with multi-dimensional reconfigurability.

Dynamic reconfiguration of photonic function is one of the hallmarks of optofluidics. A number of approaches have been taken to implement optical tunability in microfluidic devices. However, a device architecture that allows for simultaneous high-performance microfluidic fluid handling as well as dynamic optical tuning has not been demonstrated. Here, we introduce such a platform based on a combination of solid- and liquid-core polydimethylsiloxane (PDMS) waveguides that also provides fully functioning microvalve-based sample handling. A combination of these waveguides forms a liquid-core multimode interference waveguide that allows for multi-modal tuning of waveguide properties through core liquids and pressure/deformation. We also introduce a novel lifting-gate lightvalve that simultaneously acts as a fluidic microvalve and optical waveguide, enabling mechanically reconfigurable light and fluid paths and seamless incorporation of controlled particle analysis. These new functionalities are demonstrated by an optical switch with >45 dB extinction ratio and an actuatable particle trap for analysis of biological micro- and nanoparticles.

Research highlights: translating chips.

Microfluidic and microfabricated systems are providing key functionalities in diagnostic and therapeutic scenarios, translating beyond the research laboratory to pre-clinical animal studies and clinical studies with patients. Here, we highlight a recent study making use of miniaturization and automation in the development of a smartphone-integrated point-of-care diagnostic to detect antibodies to infectious diseases in a global health setting. We also review an intraocular implanted diagnostic system for glaucoma that relies on imaging the location of a fluid meniscus in a microchannel to readout pressure within the eye. Developments in low-cost and highly functional consumer electronic systems (e.g. smartphones in both highlighted works) has led to a continuing trend to incorporate such technologies with microfluidic fluid handling capabilities to achieve complete diagnostic solutions. We conclude with another implanted microdevice that delivers drug locally to tumors through electroosmotic flow and electromigration of charged drug species, which allows high drug concentrations near a tumor or resected tumor site while preventing high systemic levels associated with significant side-effects. The maturity of microsystem components are now allowing integration into fully functional systems that are poised to reach the clinic in a variety of forms - diagnostic to therapeutic.

Nanorheology of liquid crystal thin films confined between interfaces with anisotropic molecular orientations

The hydrodynamic properties of confined liquids play a significant role in the transportation of fluids in microfluidics, nanofluidics, and flows in porous media so on. In this paper, the effective viscosities of 4-Cyano-4′-pentyl biphenyl (5CB) liquid crystals (LCs) confined in a slab geometry with interfaces of anisotropically oriented molecules were investigated by a quartz crystal microbalance (QCM). A novel nanocell was fabricated onto the QCM substrate chip resulting in a 520-nm-thick slab geometry for viscosity measurement. Rubbed polyimide layer was spinning coated onto the nanocell interfaces to obtain different combinations of interfacial molecular orientations of the added 5CB LCs. The resulted effective viscosity of 5CB LCs increased by ~14 % on the interface with LC molecules oriented vertically to the shearing direction. However, it decreased on the substrate interface with LC molecules parallel along the shearing direction and decreased up to ~58 % when the LCs was confined in the nanocell with both parallel oriented interfaces. A varying magnitude of ~300 % in LC effective viscosity could be obtained by tailoring the interfacial molecular orientations. We also demonstrated that the shear resistance applied on the interface is predominated by the liquid microstructure within nanometers distance from the wall, but weakly influenced by that far from the local interface. The results were analyzed in terms of LC intermolecular friction and the predominance of the interfacial molecules at nanoscale, which are of the utmost importance for fluid transportation in microfluidics, in porous media, or in boundary lubrications.

Component design and testing for a miniaturised autonomous sensor based on a nanowire materials platform

We present the design considerations of an autonomous wireless sensor and discuss the fabrication and testing of the various components including the energy harvester, the active sensing devices and the power management and sensor interface circuits. A common materials platform, namely, nanowires, enables us to fabricate state-of-the-art components at reduced volume and show chemical sensing within the available energy budget. We demonstrate a photovoltaic mini-module made of silicon nanowire solar cells, each of 0.5 mm2 area, which delivers a power of 260 μW and an open circuit voltage of 2 V at one sun illumination. Using nanowire platforms two sensing applications are presented. Combining functionalised suspended Si nanowires with a novel microfluidic fluid delivery system, fully integrated microfluidic---sensor devices are examined as sensors for streptavidin and pH, whereas, using a microchip modified with Pd nanowires provides a power efficient and fast early hydrogen gas detection method. Finally, an ultra-low power, efficient solar energy harvesting and sensing microsystem augmented with a 6 mAh rechargeable battery allows for less than 20 μW power consumption and 425 h sensor operation even without energy harvesting.

Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion–solvent diffusion

Monodisperse polylactide (PLA) microspheres were continuously fabricated by microfluidic emulsification and subsequent dilution in water. The diameter was precisely tuned from 6 to 50 μm by changing the flow rate of the fluids in microfluidics or the PLA concentration in the dispersed phase. The use of amphiphilic oil-soluble poly(ethylene glycol)-b-polylactide (o-PEG–PLA) as a matrix resulted in a highly porous microsphere morphology, and the porosity was controlled by blending PLA. Therefore, monodisperse PLA microspheres with the predetermined surface porosity were continuously produced by just enough reagents and energy.