Microfluidic Applications Research Articles

Towards Small Scale: Overview and Applications of Microfluidics in Biotechnology.

Thanks to recent and continuing technological innovations, modern microfluidic systems are increasingly offering researchers working across all fields of biotechnology exciting new possibilities (especially with respect to facilitating high throughput analysis, portability, and parallelization). The advantages offered by microfluidic devices-namely, the substantially lowered chemical and sample consumption they require, the increased energy and mass transfer they offer, and their comparatively small size-can potentially be leveraged in every sub-field of biotechnology. However, to date, most of the reported devices have been deployed in furtherance of healthcare, pharmaceutical, and/or industrial applications. In this review, we consider examples of microfluidic and miniaturized systems across biotechnology sub-fields. In this context, we point out the advantages of microfluidics for various applications and highlight the common features of devices and the potential for transferability to other application areas. This will provide incentives for increased collaboration between researchers from different disciplines in the field of biotechnology.

Design and analysis of a novel Bi-layer curved serpentine chaotic micromixer for efficient mixing

Mixing enhancement at the micro-scale is important in microfluidics applications, including biological and chemical analysis systems. Herein, two new designs of chaotic micromixers named Bi-layer Curved Serpentine (BCS1 and BCS2) micromixers were proposed. The performance analyses were performed by solving the steady equations of conservation of mass and momentum along with the convection-diffusion equation numerically at Reynolds numbers of 0.1–200. These micromixers consisted of curved serpentine channels stacked in two layers with different combinations of curved channel radii in each layer. They exhibited efficient homogenization with a comparatively lower pressure drop and a higher mixing cost. The main mixing processes were Dean vortices, extensional flow, and chaotic advection caused by asymmetrical vortices. The BCS1 micromixer, which has a constant but unequal radius of the serpentine channel in the top and bottom layers, showed the best mixing. BCS1 and BCS2 micromixers showed significantly higher mixing indices than the simple serpentine (SS) micromixer. Furthermore, the BCS1 micromixer provided a higher mixing cost by showing similar mixing at a ∼53% lesser pressure drop than a previously proposed serpentine micromixer. BCS1 and BCS2 micromixers showed mixing index values higher than 0.80 at Re ≥ 40 and Re ≥ 60, respectively.

Application of Microfluidics for Bacterial Identification.

Bacterial infections continue to pose serious public health challenges. Though anti-bacterial therapeutics are effective remedies for treating these infections, the emergence of antibiotic resistance has imposed new challenges to treatment. Often, there is a delay in prescribing antibiotics at initial symptom presentation as it can be challenging to clinically differentiate bacterial infections from other organisms (e.g., viruses) causing infection. Moreover, bacterial infections can arise from food, water, or other sources. These challenges have demonstrated the need for rapid identification of bacteria in liquids, food, clinical spaces, and other environments. Conventional methods of bacterial identification rely on culture-based approaches which require long processing times and higher pathogen concentration thresholds. In the past few years, microfluidic devices paired with various bacterial identification methods have garnered attention for addressing the limitations of conventional methods and demonstrating feasibility for rapid bacterial identification with lower biomass thresholds. However, such culture-free methods often require integration of multiple steps from sample preparation to measurement. Research interest in using microfluidic methods for bacterial identification is growing; therefore, this review article is a summary of current advancements in this field with a focus on comparing the efficacy of polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and emerging spectroscopic methods.

Design optimization and performance tuning of curved-DC-iDEP particle separation chips

Many microfluidics methods have been proposed for filtering, focusing, and separation, among which DC-iDEP is accounted as one of the most straightforward approaches from fabrication and implementation aspects. Former studies focused on improving the geometrical features of simple/straight iDEP channels. This paper concentrates on developing a versatile tool that helps reduce the design time and optimize the performance of curved iDEP channels for continuous separation. A numerical model for predicting the particle trajectories was validated by image processing of Polystyrene (PS) particles in a curved channel. To lower the applied voltage and/or footprint, the shape of hurdles integrated with the channel was investigated by proposing basic shapes and algorithmic design optimization approaches. From the basic geometries, rectangular hurdles were found to be the most effective shape for particle manipulation with an efficiency enhancement of 10% compared to circular and triangular hurdles. Automatic investigation suggests the optimization of the shape and widths of hurdles can even further increase the performance by 11%. Multi-objective separation optimization (MOSO) in curved channels exhibits that an increase in aspect ratio from 2 to 8 improves the separation quality at higher voltages. The proposed method can be utilized in various microfluidic applications via minor design modifications.

3D‐Printed Centrifugal Pump Driven by Magnetic Force in Applications for Microfluidics in Biological Analysis (Adv. Healthcare Mater. 24/2022)

Dynamic Cell Cultures Article 2200593 by Shoji Takeuchi and co-workers proposes a 3D-printed centrifugal pump driven by magnetic force. Precise control of the flow rate and a wide range and variety of flow profiles are achieved by controlling the rotational speed of the motor. Compact size enables simple setups within commercially available culture dishes and tubes. Moreover, demonstrations of laminar flow production and perfusion culture are presented for biological applications in microfluidic devices.

Improvement in therapeutic activity and stability of neuropeptide Y using PEGylated polyplexes in MCF-7 and MDA-MB-231 cells

The transport of peptides and nucleic acid using polyplexes as carrier system shows potential in the gene and DNA-based delivery systems to treat various conditions such as infection, inflammation, cancer, etc. The present study focused on the development of neuropeptide Y-loaded polyplexes from cationic polymer coated with PEG 2000 by application of microfluidics. The PEGylated polyplexes were statistically optimized by 3-Level factorial design with entrapment efficiency of 87.06±6.15% and in-vitro release of neuropeptide Y of 83.71±6.31% for 24 h. These polyplexes displayed 15.5% of α-helical content with no shift in the β-sheet content from Reed reference using circular dichroism spectroscopy. The FTIR and NMR studies confirmed the polymeric reaction with neuropeptide Y in PEGylated polyplexes by displaying the presence of PEG-NHS interaction with PEG-PEI grafting. The formulation PPN showed G0G1 cell arrest with an IC 50 value of 4.98±0.5 μg/mL and 54.46±6.33% apoptosis on the MCF-7 and IC 50 value of 6.23±2.11 μg/mL and 50.23±5.71% apoptosis on MDA-MD-231 cells by upregulating phosphor-p38 MAPK pathway. The PEGylated polyplexes were found to be stable for 6 months and displayed particle size 360.52 ± 8.35 nm at 5°C and 368.02 ± 7.36 nm at 25°C due to formation of steric shield by PEGylation on the structures of polyplexes. The animals study showed no toxicity on administration of formulation PPN via intravenous route and better t 1/2 (5.79 h) and AUC (84888.63 pg/mL*min) without mortality. Hence, PEGylated polyplexes emerge as a novel, effective and economical nanocarrier delivery system contributing towards long-term stability, less toxicity with significant apoptotic action on breast cancer cell lines.

Si3N4 ceramics with embedded microchannel structures fabricated by high-precision additive manufacturing based on computational fluid dynamics simulations

Ceramics with microchannel structures are primarily used in heat exchangers and microfluidic device applications in harsh environments, such as high-temperature and corrosive conditions. However, the high cost the difficulty of fabrication limits the development of microchannel ceramics, especially the embedded microstructures. Here, a strategy of fabricating the Si 3 N 4 ceramics with embedded microchannel structures by material extrusion is reported. We employ the finite element method to analyze the computational fluid dynamics (CFD) model of the material extrusion process with a pressure-actuated system, and the simulation results are validated by comparing with the experimental average flow velocity under different air pressures. Due to the accurate prediction of the flow rate and the excellent shape-retention of Si 3 N 4 inks, the shape and size of the filaments are controllable. Therefore, microchannel structures with a size of 0.09 – 0.94 mm were fabricated by different nozzles, and the flow direction and the channel density can be freely designed by the printing paths. Our results provide guidelines of setting parameters for accurately printing the structures as designed.

A passive and programmable 3D paper-based microfluidic pump for variable flow microfluidic applications.

Paper has attracted significant attention recently as a microfluidic component and platform, especially in passive pumping devices due to its porous and uniform absorbing nature. Many investigations on 1D and 2D fluid flows were carried out. However, no experimental work has been reported on the three-dimensional effect in porous geometry to improve pumping characteristics in microchannels. Therefore, in this study, the fluid flow in 3D paper-based passive pumps was investigated in microchannels using cylindrical pumps. The effect of pump diameter, porosity, and programmability was investigated to achieve desired flow variations. The results indicated that the flow rate of water increased with an increase in the diameter and porosity of paper pumps. Maximum flow rates achieved for 14 mm diameter pumps of 0.5 and 0.7 porosities were 5.29 mm3/s (317.4 μl/min) and 6.97 mm3/s (418.2 μl/min), respectively. The total volume of fluid imbibition ranged between 266 and 567 μl for 8 and 14 mm diameter pumps, respectively. Moreover, 3D passive pumps can transport larger volumes of liquid with an improved flow rate, programmability, and control, in addition to being inexpensive and simple to design and fabricate. Most importantly, a single 3D paper pump showed an increasing, decreasing, and constant flow rate all in a single microchannel. With these benefits, the passive pumps can further improve the pumping characteristics of microfluidic platforms enabling a cost effective and programmable point-of-care diagnostic device.

A Quality Factor Enhanced Microwave Sensor Based on Modified Split-Ring Resonator for Microfluidic Applications

A common-mode (CM) suppression-based passive microwave measurement system for microfluidic applications is proposed in this article. The proposed system contains three parts, including differential microwave microstrip sensor, phase shifter, and power divider. The differential structure of the proposed microstrip sensor is composed of two split-ring resonator (SRR)-based microstrip sensors and four 3-D metallic walls. Interdigital capacitances (IDCs) are inserted between two SRRs to enhance the density of electric field. Moreover, two 3-D metallic walls are erected on both sides of each IDC, which can increase the concentration of electric field further. Power divider, phase shifter, and differential structure constitute the measurement system. Assuming that a signal with frequency of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${f}_{{0}}$ </tex-math></inline-formula> is input into input port, and going through by power divider, the CM signals will be generated. Then, passing by phase shift, differential structure, and combiner to output port, theoretically, when the phase difference between two branches is 180° at <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${f}_{{0}}$ </tex-math></inline-formula> , the corresponding magnitude of output signal will be zero at <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${f}_{{0}}$ </tex-math></inline-formula> . Therefore, the transmission coefficient will be infinitesimal at <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${f}_{{0}}$ </tex-math></inline-formula> (CM signals are suppressed), and an ultrahigh <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${Q}$ </tex-math></inline-formula> will be obtained. An equivalent circuit model is presented to reveal the operating principle of the sensor. The variations of relative frequency shift and normalized <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${Q}$ </tex-math></inline-formula> are adopted to extract the complex permittivity of liquid sample. In the experiment, the sensitivity of detecting real permittivity is about 0.05%, and a high <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${Q}$ </tex-math></inline-formula> of about 1432 is realized. All in all, the proposed microwave sensor has a huge superiority over some previously reported ones.

Dynamic change in the shape of the droplet placed on superhydrophobic Cu-based surface through electrochemical reaction under negative bias potential

The interdependence between the redox reactions capable of changing surface composition and the wettability is central to a wide array of applications ranging from electrochemical energy production and storage technologies to wettability control for microfluidic applications. In this study, we have demonstrated that the shape of a potassium chloride-based electrolyte droplet placed on a superhydrophobic copper–copper oxide surface changes dynamically upon the application of negative bias potentials. The copper–copper oxide based superhydrophobic surface with micro-nano structured roughness features was prepared by the electrodeposition process. Studies were conducted at different bias potentials, ranging from −0.6 V to −0.9 V, and the change in the droplet shape based on the contact angle and baseline size is presented. The results show that an increase in the magnitude of the bias potential results in a higher amount of contact angle reduction and baseline size increase over the same duration. The electroreduction of the copper oxide present on the surface is attributed to the change in the droplet shape.

Cell-Mimic Directional Cargo Transportation in a Visible-Light-Activated Colloidal Motor/Lipid Tube System.

Active tether and transportation of cargoes on cytoskeletal highway enabled by molecular motors is key for accurate delivery of vesicles and organelles in the complex intracellular environment. Here, a hybrid system composed of colloidal motors and self-assembled lipid tubes is designed to mimic the subcellular traffic system in living cells. The colloidal motors, composed of gold-coated hematite, display light-activated self-propulsion tunable by the light intensity and the concentration of hydrogen peroxide fuel. Importantly, the motors show light-switchable binding with lipid cargoes and attachment to the lipid tubes, whereby the latter act as the motor highways. Upon assembly, the colloidal motor/lipid tube system demonstrates directional delivery of lipid vesicles, emulating intracellular transportation. The assembly and function of the hybrid system are rationalized by a cooperative action of light-triggered electrophoretic and hydrodynamic effects, supported by finite element analysis. A synthetic analog of the biological protein motor/cytoskeletal filament system is realized for the manipulation and delivery of different matter at the microscale, which is expected to be a promising platform for various applications in materials science, nanotechnology, microfluidics, and synthetic biology.

Plasmon-enhanced rotational dynamics of anisotropic core-shell polymeric-metallic microparticles

The development of efficient and cost-effective micromachines is a challenge for applied and fundamental science, given their wide fields of usage. Light is a suitable tool to move small objects in a noncontact way, given its capabilities in exerting forces and torques. However, when complex manipulation is required, micro-objects with proper architecture could play a specific role. Here we report on the rotational dynamics of core-shell particles, with a polymeric nematic core of ellipsoidal shape capped by Au nanoparticles. They undergo a peculiar synchronous spinning and orbital motion when irradiated by a simple Gaussian beam, which originates from the coupling of the metallic nanoparticles’ optical response and the core anisotropies. The rotation capabilities are strongly enhanced when the trapping wavelength lies in the plasmonic resonance region: indeed, the spin kinetic energy reaches values two orders of magnitude larger than the one of bare microparticles. The proposed strategy brings important insights into optimizing the design of light controlled micro-objects and might benefit applications in microfluidics, microrheology, and micromachining involving rotational dynamics.

Fast and Simple Fabrication of Multimaterial Hierarchical Surfaces Using Acoustic Assembly Photopolymerization (AAP)

AbstractMultimaterial surfaces with hierarchical features have many potential applications in self‐cleaning, droplet manipulation, microfluidics, and biomedicine, owing to their wide range of functionalities induced by structural and material contrasts. Here, a fast and sustainable manufacturing method, acoustic assembly photopolymerization (AAP), is presented for productions of such surfaces. In the novel AAP process, an external acoustic field is used to assemble microparticles to microsized patterns, while the photocuring is combined with the acoustic assembly to produce multilevel hierarchical features, such as cones and wrinkles ranging from nanometer to micrometer. The mechanism underlying the proposed multimaterial surface structuring technique is discussed, and the relationship between process parameters and surface structures is modeled. Effects of surface material composition patterns and surface topology on the hydrodynamic properties are studied. To demonstrate potential applications, three microreactors are designed and automated droplet manipulations are demonstrated. The application of the proposed surface manufacturing approach is further extended to fog harvesting. The AAP technology and the fabricated multimaterial hierarchically‐structured surfaces demonstrated in this study can be employed in many other advanced applications in microfluidics, tissue engineering, and also potentially many other fields such as mechanical systems and battery systems.

Design of OCSRR-Based Differential Microwave Sensor for Microfluidic Applications

In this article, a high-sensitivity differential microwave sensor based on open comprehensive split-ring resonator (OCSRR) is proposed to extract the complex dielectric constant of liquid samples. An OCSRR structure is etched on the metal plate attached to the upper layer of the substrate. In addition, the outer ring of OCSRR adopts a hexagonal structure to reduce the original capacitance of OCSRR, and the inner ring of OCSRR adopts a rectangular structure to facilitate optimization and obtain the highest electric field intensity. The polydimethylsiloxane (PDMS) microfluidic channel is placed on the side of the outer ring with high electric field intensity and injects different concentrations of water–ethanol mixture. During resonance, the electric field is concentrated along the slit where the microfluidic channel is located. When the liquid sample is injected, the corresponding reflection coefficient changes. The designed sensor is fabricated and tested, and the experimental results are in good agreement with the simulation results. Compared with the previous similar sensors, the sensor can suppress the influence of environmental factors and has an average high sensitivity of 0.88%.

In-line measurements of the physical and thermodynamic properties of single and multicomponent liquids.

Microfluidic devices are becoming increasingly important in various fields of pharmacy, flow chemistry and healthcare. In the embedded microchannel, the flow rates, the dynamic viscosity of the transported liquids and the fluid dynamic properties play an important role. Various functional auxiliary components of microfluidic devices such as flow restrictors, valves and flow meters need to be characterised with liquids used in several microfluidic applications. However, calibration with water does not always reflect the behaviour of the liquids used inthe different applications. Therefore, several National Metrology Institutes (NMI) have developed micro-pipe viscometers for traceable inline measurement of the dynamic viscosity of liquids used in flow applications aspart of the EMPIR 18HLT08 MeDDII project. These micro-pipe viscometers allow the calibration of any flow device at different flow rates and the calibration of the dynamic viscosity of the liquid or liquid mixture used under actual flow conditions. The validation of the micro-pipe viscometers has been performed either with traceable reference oils or with different liquids typically administered in hospitals, such as saline and/or glucose solutions or even glycerol-water mixtures for higher dynamic viscosities. Furthermore, measurement results ofa commercially available device and a technology demonstrator for the inline measurement of dynamic viscosity and density are presented in this paper.

An Improved Split-Ring Resonator-Based Sensor for Microfluidic Applications.

This study proposes an ultrahigh-sensitivity split-ring resonator-based microwave sensor for retrieving the complex permittivity of liquid samples. An interdigital capacitor structure was used to expand the sensing area and the sensitivity. A defected ground structure and A parallel dual split-ring resonator were introduced to improve the quality factor. A polydimethylsiloxane microfluidic channel substrate was placed above the interdigital capacitor structure. The channel route coincided with the interdigital gap to fully utilize the strong electric field. Ethanol-water solutions with varying ethanol fractions were injected into the channel as the testing liquid. It was demonstrated that the variation in resonant frequency can be used to retrieve the dielectric properties of liquid samples. The proposed sensor used a small liquid volume of ~0.68 μL and provided values in good agreement with the reference data.

Active spatial control of photothermal heating and thermo-actuated convective flow by engineering a plasmonic metasurface with heterodimer lattices

Thermo-plasmonics, using plasmonic structures as heat sources, has been widely used in biomedical and microfluidic applications. However, a metasurface with single-element unit cells, considered as the sole heat source in a unit cell, functions at a fixed wavelength and has limited control over the thermo-plasmonically induced hydrodynamic effects. Plasmonic metasurfaces with metal disk heterodimer lattices can be viewed to possess two heat sources within a unit cell and are therefore designed to photo-actively control thermal distributions and fluid dynamics at the nanoscale. The locations of heat sources can be switched, and the direction of the convective flow in the central region of the unit cell can be reversed by shifting the wavelength of the excitation source without any change in the excitation direction or physical actuation of the structural elements. The temperature and velocity of a fluid are spatiotemporally controlled by the wavelength selectivity and polarization sensitivity of the plasmonic metasurface. Additionally, we investigate the effects of geometric parameters on the surface lattice resonances and their impact on the temperature and fluid velocity of the optofluidic system. Our results demonstrate excellent optical control of these plasmonic metasurface heating and thermal convection performances to design flexible platforms for microfluidics.

Simultaneous measurement of microscale fluid viscosity, temperature, and velocity fields by tracking Janus particle on microparticle image velocimetry

Multifunctional sensing capability enables a comprehensive understanding of the unknown target to be measured. Given that fluid viscosity, temperature, and velocity fields are usually coupled parameters in a system, simultaneous measurement of the three environmental factors can prevent cross-talk and improve reliability. However, the task is apparently challenging because of the microscale targets. A technique combining microparticle image velocimetry and Janus particles was developed in this study to address such demand. With the rotational diffusivity and particle trajectories measured by the proposed technique and an empirical water-based viscosity-temperature relationship, the three unknown variables in a microfluidic environment were solved. The blinking frequency was derived using the Hilbert Huang Transform. Compared with those in a static and uniform temperature field, the measured data had good agreement with the predicted values. However, the agreement was impaired when the heating rate exceeded 0.34 °C/s. The optimal temperature range was found between 10 °C and 40 °C in the water-based solution. For a steady-state and nonuniform temperature field, two-dimensional (2D) numerical simulations of three linear temperature gradients were also studied. Results showed that the deviation increased as the temperature gradient increased or was near the low-temperature region. The same procedure was eventually applied to a real thermophoretic flow induced by an IR laser in a microchip. The 2D fluid viscosity, temperature, and velocity fields in the microchip were successfully obtained by tracking 10 particles. The potential of the approach provides insight into understanding some microfluidic applications with mild changes in temperature or creeping flow. This study combined µPIV with Janus particles to achieve simultaneous measurement of 2D microscale fluid viscosity, temperature, and velocity fields. By simply tracking the particles, particle trajectories and blinking signal were obtained. Both parameters provided sophisticated information of particle velocity and rotational diffusivity. With the information, the viscosity and temperature were hence derived from the empirical viscosity–temperature relationship and the Stokes-Einstein-Debye relation. The velocity was derived alone based on the conventional cross-correlation algorithm. • Using Janus particles as tracers to provide dynamic information of blinking signal and trajectories. • Simultaneous measurement of whole field fluid viscosity, temperature, and velocity at the microscale. • Extraction of the frequency spectrum out of blinking signal by Hilbert Huang Transform. • A measurable temperature range between 10 °C and 40 °C.

Analysis of Mass Concentration and Morphology of Fume Particles during ECDM of CFRP Composites

Electrochemical discharge machining (ECDM) is a hybrid method used to generate micro-features in hard and brittle materials (glass, ceramics, and composites) in aerospace, microelectromechanical systems (MEMS), and microfluidic applications. A significant improvement was observed in ECDM process but the effect of the process on the health of working operator are rarely investigated. Sustainability in manufacturing is a major concern for a better environment and safety of human operators. In this paper, analysis of fumes mass concentration (FMC), size and morphology of fume particles, and composition of fume particles along with their biological effects are studied during ECDM of CFRP composites. FMC was calculated by varying the concentration of electrolyte from 20 to 50% and duty cycle from 60 to 90% for a fixed sampling duration of 30 minutes. SEM images indicated the presence of spherical, irregular, and loosely packed fumes particles in the fumes generated during machining. EDS was also performed to study the chemical composition of fumes particles.

Droplet Tweezers Based on the Hydrophilic-Hydrophobic Interface Structure and Their Biological Application.

Droplet controllable operation has wide applications in microfluidics, biomedicine, microreactors, and other fields. Droplets can spontaneously transfer from a high-energy state to a low-energy state, but how to reverse transfer the droplets is a difficult task. In this article, we use a special hydrophilic-hydrophobic interphase structure (HHIS) to achieve this reverse transfer. We specifically study the critical conditions under which droplet transfer can be achieved. The length of the hydrophilic surface in this structure and the hydrophilic/hydrophobic properties of the surface must be in the appropriate range. Based on this, an optimized structure used to transfer droplets was designed. Finally, we carried out research on biological applications and successfully achieved the transfer of droplets from zebrafish eggs and zebrafish larvae. This unique method is low-cost, biofriendly, and highly applicable to various surfaces, illustrating the great potential in chemical and biological analysis.