Microfluidics enables generating series of isolated droplets for high-throughput screening. As many biological/chemical solutions are of shear thinning non-Newtonian nature, we studied non-Newtonian droplet generation to improve the reliability of simulation results in real-life assays. We considered non-Newtonian power-law behaviour for Xanthan gum aqueous solution as the dispersed phase, and Newtonian canola oil as the continuous phase. Simulations were performed in OpenFOAM, using the inter foam solver and volume of fluid (VOF) method. A cross-junction geometry with each inlet and outlet channel height (H) and width (W) equal to 50 micrometers with slight contractions in the conjunctions was used to gain a better monodispersity. Following validation of the numerical setup, we conducted a series of tests to provide novel insight into this configuration. With a capillary number, of 0.01, dispersed phase to continuous phase flow-rate ratio of 0.05, and contact angle of 160°, simulations revealed that, by increasing the Xanthan gum concentration (0, 800, 1500, 2500 ppm) or, in other words, decreasing the n-flow behaviour index from 1 to 0.491, 0.389, and 0.302 in power-law model, (a) breakup of the dispersed phase thread occurred at 0.0365, 0.0430, 0.0440, and 0.0450 s; (b) the dimensionless width of the thread at the main channel entrance increased from 0 to 0.066, 0.096, and 0.16; and (c) the dimensionless droplet diameter decreased from 0.76 to 0.72, 0.68, and 0.67, respectively. Our next plan is to study effect of shear-thinning behaviour on droplet generation in different Ca and flow-rate ratios.
: The use of microalgae as a biomass source for biofuel production has drawn the attention of many scientists due to several associated environmental advantages over conventional terrestrial crops, including microalgae growing using wastewaters and a higher CO 2 fixation rate, contributing to the reduction of atmospheric concentration. Consequently, a reliable cytoplasmic lipid screening process in microalgae is a valuable asset for harvesting optimization in mass production processes. In this study, the heterogeneous cytoplasmic lipid content of Neochloris oleoabundans was dielec-trophoretically assorted in a microfluidic device using castellated carbon microelectrodes. The ex-periments carried out over a wide frequency window (100 kHz to 30 MHz) at a fixed amplitude of 7 VPP showed a significant contrast between the dielectrophoretic behavior of high lipid content and low lipid content cells at the low frequency range (100–800 kHz). A weak response for the mid and high frequency ranges (1–30 MHz) was also identified for high and low lipid content samples, allowing one to establish an electrokinetic footprint of the studied strain. These results suggest that the development of a reliable screening process for harvesting optimization is possible through a fast and straightforward mechanism, such as dielectrophoresis, which is a low-cost and easy-to-machine material that employs glassy carbon. The experimental setup in this study involved in vitro culturing of nitrogen-replete (N+) and nitrogen-deplete (N-) cell suspensions to promote low and high lipid production in cells, respectively. Cell populations were monitored using spectrophotom-etry, and the resulting lipid development among cells was quantified by Nile red fluorescence.
Wearable electronics are changing healthcare and increasing possibilities for human-machine interfaces. Soft electronics, directly mounted on the skin, can monitor long-term heart rate trends or direct smart prosthetics' motion. However, these capabilities are only as good as the signal quality obtained. These wearable devices are worn in the real world, often suffering from motion artifacts not previously found when measured in a stationary setting such as a clinic or laboratory. Motion artifacts can mimic many biosignals by having a similar amplitude and frequency range, making them hard to filter out. A significant source of motion artifacts is from relative motion between the sensor and the signal source. Given human tissue's elastic nature, most body-mounted sensors undergo more relative motion than on a comparable rigid machine. Here, this work introduces a comprehensive study of materials, methods, and optimized designs that can significantly reduce motion artifacts via strain isolation, increased adhesion, and enhanced breathability for long-term recordings. Skin strain is another source of motion artifacts that can disturb electrodes' contact impedance and temporarily change the biopotential within the skin. We present a prototype electrocardiogram (ECG) device that uses a strain isolating layer to reduce skin strain at the electrode. This strategic integration of soft and hard materials reduces motion artifacts by stabilizing the electrode, while allowing freedom of movement elsewhere to maintain gentle contact with the skin. These solutions are demonstrated for long-term ECG collection but have application for any skin-mounted wearable device.
Magnetic microrobots with versatile mechanical motion will enable many ex- and in vivo applications. Unfortunately, monolithic integration of multiple functions in a streamlined microrobotic body is still challenging due to the compromise between fabrication throughput, device footprints, and material choices. In this talk, I will present a unified framework architecture for microrobotic functionalization to enable magnetically steered locomotion, chemical sensing and in vivo tracking. This has been achieved through stratifying stimuli-responsive nanoparticles in a hydrogelmicro-disk. We uncovered the key mechanism of leveraging spatially alternating magnetic energy potential to control a Euler’s disk-like microrobot to locomote swiftly on its sidewall. The results suggest great potential for microrobots to locomote while cooperating a wide range of functions, tailorable for universal application scenarios.
Over the last two decades, we have gained more and more insight into how to convert patterned polymer precursors into predicable 3D carbon shapes using pyrolysis/carbonization (carbon origami are a more recent example). Over the last four years, we have started gaining control over the internal carbon microstructure and its functionality. The key to the latter is a precise control of the polymer precursor chains and the exact polymer atomic composition of the polymer before and during pyrolysis. Contradicting Rosalind Franklin, we have found that it is possible to graphitize even non-graphitizing carbons, simply by applying mechanical stresses to align the polymer precursor chains and stabilizing them in position before pyrolysis. Perhaps the most surprising outcome of this work is the demonstration of the conversion of PAN fibers through pyrolysis into turbostratic graphene-suspended wires with diameters as small as 2 nanometers. The suspended graphene bridges have a conductivity similar to that of multiwall carbon nanotubes (MWCNTs), a Young’s modulus of >400 GPa, and electrochemically the material behaves similarly to graphene doped with nitrogen. The latter material represents a very electroactive electrode ideally suited for energy and sensing applications. The current fabrication process for graphene doped with nitrogen is lengthy and complicated; ours is a one-step, simple process that is easily scalable.
(1) The advent of micro/nanorobotics promises to transform the physical, chemical, and biological domains by harnessing opportunities otherwise limited by size. Most notable is the biomedical field, in which the ability to manipulate micro/nanoparticles has numerous applications in biophysics, drug delivery, tissue engineering, and microsurgery. (2) Acoustics, the physics of vibrational waves through matter, offers a precise, accurate, and minimally invasive technique to manipulate microrobots or microparticles (stand-ins for microrobots). One example is through the use of flexural vibrations induced in resonant structures such as Chladni plates. (3) In this research, we developed a platform for precise two-dimensional microparticle manipulation via acoustic forces arising from Chladni figures and resonating microscale membranes. The project included two distinct phases: (i) macroscale manipulation with a Chladni plate in air; and (ii) microscale manipulation using microscale membranes in liquid. In the first phase (macroscale in air), we reproduced previous studies in order to gain a better understanding of the underlying physics and to develop control algorithms based on statistical modeling techniques. In the second phase (microscale in liquid), we developed and tested a new setup using custom microfabricated structures. The macroscale statistical modeling techniques were integrated with microscale autonomous control systems. It is shown that control methods developed on the macroscale can be implemented and used on the microscale with good precision and accuracy.
Silicon Carbide (SiC) is a highly versatile semiconductor material that has long been used in harsh applications such as space, corrosive and high-temperature environments and, more recently, the human body. The impressive and highly advantageous materials properties of SiC have shown that this material is ideally suited for medical applications due to its proven bio- and hemocompatibility. Indeed, SiC appears to be quite unique for use in the human brain whereby implants made using SiC coatings have demonstrated vastly improved performance with virtually no human body immune response which plagues Silicon technology. After over two decades of focused research and development SiC is now ready for use in the healthcare sector and this paper provides an up to date assessment of SiC devices for long-term human use. First the plethora of applications that SiC is uniquely positioned for in human healthcare is reviewed so that healthcare professionals will be fully aware of the significant opportunities now possible with the rapid development of this technology. Next progress in two areas will be presented: Neural implants and deep-tissue cancer therapy using SiC nanotechnology.
Phytopathological adversities are often attributable to human activities (as a consequence of the globalization of trade or tourism mass, changes in common agricultural practices and climate change), resulting in food losses due to pathogens such as fungi, bacteria, viruses, etc. For this reason, we are developing lab-on-chip devices as diagnostic tools to identify and manage phytopathological problems caused by infectious agents capable of spreading in agro-ecosystems, such as the Xylella fastidiosa epidemic in Puglia [1] or other bacteriosis and virosis such as Grapevine leafroll-associated virus 3 (GLRaV-3). [...]
The rapid detection of hazardous bacteria is important for healthcare situations, where such identification can lead to substantial gains for patient treatment and recovery and a reduced usage of broad-spectrum antibiotics. Potential biosensors must be able to provide a fast, sensitive and selective response with as little sample preparation as possible. Indeed, some of these pathogens, such as Staphylococcus aureus, can be yet harmful at very low concentrations in the blood stream, e.g., below 10 colony forming units per mL (CFU/mL). These stringent requirements limit the number of candidates, especially for point-of-care applications. Amongst several biosensing techniques, optical sensing using porous silicon (PSi) substrate has been widely suggested in recent years thanks to unique features such as a large surface area, tunable optical characteristics, and above all relatively easy and affordable fabrication techniques. In most configurations, PSi optical biosensors are close-ended porous layers; this limits their sensitivity and responsiveness due to diffusion-limited infiltration of the analytes in the porous layer. Also, PSi is a reactive material, its oxidation in buffer solutions results in time-varying shifts. Despite its attractive properties, several challenges must still be overcome in order to reach practical applications. Our work addresses three main improvement points. The first one is the stability over time in saline solutions helped by atomic layer deposition of metal oxides inside the pores. Besides a better stability, our solution is helping with an increase of the optical signal to noise ratio, thus reducing the limit of detection. The second one is to perform the lysis of the bacteria prior to its exposure to the sensor, such that the selective detection is based upon the percolation of bacterial residues inside the pores rather than the bacteria themselves. The third one is to remove the bulk silicon below a PSi layer to create a membrane, that allows for flow-through of the analytes, thus enhancing the interactions between the lysate and the sensor’s surface. This approach allows us to avoid the step of surface functionalization used in classical biosensors. We tested thanks to these improvements the selective detection of Bacillus cereus lysate with concentrations between 103 and 105 CFU/mL. Future works are dedicated to further improvements, including optical signal enhancement techniques and dielectrophoretic assisted percolation in the porous silicon membrane.
Glaucoma is the second leading cause of preventable blindness worldwide, following cataract formation. A rise in the intraocular pressure (IOP) is a major risk factor for this disease, and results from an elevated resistance to aqueous humor outflow from the anterior chamber of the eye. Glaucoma drainage devices provide an alternative pathway through which the aqueous humor can effectively exit the eye, thereby lowering the IOP. However, post-operative IOP is unpredictable and current implants are deficient in maintaining IOP at optimal levels. To address this deficiency, we are developing an innovative, non-invasive magnetically actuated glaucoma implant with a hydrodynamic resistance that can be adjusted following surgery. This adjustment is achieved by integrating a magnetically actuated microvalve into the implant, which can open or close fluidic channels using an external magnetic stimulus. This microvalve was fabricated from poly(styrene–block–isobutylene–block–styrene), or ‘SIBS’, containing homogeneously dispersed magnetic microparticles. “Micro-pencil” valves of this material were fabricated using a combination of femtosecond laser machining with hot embossing. The glaucoma implant is comprised of a drainage tube and a housing element fabricated from two thermally bonded SIBS layers with the microvalve positioned in between. Microfluidic experiments involving actuating the magnetic micro-pencil with a moving external magnet confirmed the valving function. A pressure difference of around 6 mmHg was achieved, which is sufficient to overcome hypotony (i.e., too low IOP)—one of the most common post-operative complications following glaucoma surgery.
Poly(3-hydroxybutyrate) (PHB) is a natural and biodegradable storage polyester, produced by numerous bacteria, which is considered a potential substituent for conventional plastics in the packaging industry. The improvement of the PHB material lifetime often involves mechanical and tribological characterization, which can be accurately performed on thin films. In this study, we aimed at the evaluation of the tribological properties, such as adhesion force, friction coefficient and wear resistance, of different polyester films, fabricated via the solvent casting method. Three polyester films were designed in this study, each containing 1% w/v constituents as follows: a PHBh film prepared out of the PHB, extracted from the extremely halotolerant bacteria, Halomonas elongata DSM2581T, a PHBc film fabricated using a commercially available PHB, and a PHBVc film generated using the commercial poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The spectroscopy-in-point of AFM was used for adhesion force measurement based on multiple tests performed in a matrix, and the AFM lateral operating mode was applied for friction analysis under a controlled normal load. The fabricated PHBh film presented a thickness between 5 and 7 µm, a lower adhesion force (14 nN) as well as a smaller friction coefficient (0.15) compared to the PHBc and PHBVc. The tribological investigations of PHBh film revealed a biodegradable material with low roughness, as well as small adhesion and friction forces. Further optimization can be performed for the improvement of the PHBh film by copolymerization with other polymers, polyesters, and reinforcers, thus generating a feasible material with advanced tribo-mechanical features.
Currently, lipases are one of the most widely used enzymes, especially in catalysis, mostly due to their high activity in mild conditions and wide specificity. Therefore, obtaining the highest possible catalytic activity, which can be achieved through purification, is becoming more and more important. Since most of the purification techniques are time consuming, aqueous two-phase protein extraction is often investigated as a promising alternative. Additionally, this kind of extraction can be carried out in microextractors, which provides not only a continuous processing of raw materials, but also significantly higher efficiencies due to a high surface-to-volume ratio of microchannels. Extraction with deep eutectic solvents (DESs) fulfills all green chemistry principles, because DESs are biodegradable, non-toxic, and recyclable. In this research, the aqueous two-phase system based on natural DES for continuous protein extraction in a microextractor was investigated. The impact of salt concentration on extraction efficiency was investigated in batch experiments with six different previously characterized DESs. After determination of the optimal two-phase system features, the process was transferred to a microextractor. In addition, the selected DES was tested for recyclability while the developed extraction method was verified using raw lipase produced by Thermomyces lanuginosus solid-state cultivation on hull-less pumpkin oil pomace. The highest protein extraction efficiency achieved in a batch reactor was 94.70% for 30 min, while in a microextractor, the highest extraction efficiency obtained was 98.50% for 30 s. Obviously, the extraction process was significantly intensified by continuous microextraction. Additionally, the DES used in the microextraction experiments was efficiently reused in several extraction cycles.
Several micro devices, such as micro-mirrors, are subjected to working conditions featuring alternating loadings that can possibly induce fatigue in the thin metal layers, which represent critical structural parts. The quantification of the degradation of the material properties under fatigue loading is a time-consuming task, and the effects of environmental conditions (e.g., humidity) and load characteristics (e.g., frequency, stress ratio) must be properly accounted for. In this work, we propose and assess the efficiency of an on-chip test device based on piezoelectric actuators, able to generate a time-varying (sinusoidal) strain in the mentioned thin metal layers and lead to fatigue. The aim of the research activity is the characterization of the stress/strain-induced degradation process of a thin layer located on the top of a lead zirconate titanate (PZT) actuation system. The characterization has been carried out through measurements of resistivity and roughness, carried out via an ohmmeter and a confocal microscope, respectively. The proposed testing device has shown capability to qualitatively highlight the degradation of the metal layers. A re-design of the on-chip device is also discussed in order to also carry out quantitative evaluations.
Fluids containing nanometer-sized particles (nanofluids, NFs) are potential candidates to improve the performance and efficiency of several thermal devices at micro- and macro-scale levels. However, the problem of sedimentation and instability of these colloidal dispersions has been the biggest obstacle for industrial-scale applications. In this work, two different NFs were tested using distilled water (DI-Water) as the base fluid. The first is a traditional NF formed by Al2O3 nanoparticles (NPs) with 50 nm diameter, and the second is a novel NF formed by poly (acrylic acid)-coated iron oxide NPs (Fe3O4@PAA) with ~10 nm diameter, obtained through a hydrothermal synthesis process. The main objective of this study was to evaluate the colloidal stability of these NFs over time using different volume fractions and compare it with DI-Water. Results involving sedimentation studies and zeta potential measurements showed that the proposed Fe3O4@PAA NF presents a higher colloidal stability compared to that of the Al2O3 NF. Additionally, thermal conductivity measurements were performed in both Fe3O4@PAA and Al2O3 NFs at different NP concentrations, using the transient plane source technique. Results showed higher thermal conductivity values for the Fe3O4@PAA NFs compared to those of Al2O3 NFs. However, a linear enhancement of thermal conductivity with increasing NPs concentration was observed for the Al2O3 NF over the whole range of NP concentrations tested, whereas two different regimes were observed for the Fe3O4@PAA NF.
Many lab-on-a-chip devices require a connection to an external pumping system in order to perform their function. While this is not problematic in typical laboratory environments, it is not always practical when applied to point-of-care testing, which is best utilized outside of the laboratory. Therefore, there has been a large amount of ongoing research into producing integrated microfluidic components capable of generating effective fluid flow from on-board the device. This research aims to introduce a system that can produce practical flow rates, and be easily fabricated and actuated using readily available techniques and materials. We show how an asymmetric elasto-magnetic system, inspired by Purcell’s three-link swimmer, can provide this solution through the generation of non-reciprocal motion in an enclosed environment. The device is fabricated monolithically within a microfluidic channel at the time of manufacture, and is actuated using a weak, oscillating magnetic field. The flow rate can be altered dynamically, and the direction of the resultant flow can be controlled by adjusting the frequency of the driving field. The device has been proven, experimentally and numerically, to operate effectively when applied to fluids with a range of viscosities. Such a device may be able to replace external pumping systems in portable applications.
Microneedles (MNs) have been manufactured using a variety of methods from a range of materials, but most of them are expensive and time-consuming for screening new designs and making any modifications. Therefore, stereolithography (SLA) has emerged as a promising approach for MN fabrication due to its numerous advantages, including simplicity, low cost, and the ability to manufacture complex geometrical products at any time, including modifications to the original designs. This work aimed to print MNs using SLA technology and investigate the effects of post-printing curing conditions on the mechanical properties of 3D-printed MNs. Solid MNs were designed using CAD software and printed with grey resin (Formlabs, UK) using a Form 3 printer (Formlabs, UK). MNs dimensions were 1.2 × 0.4 × 0.05 mm, arranged in 6 rows and 6 columns on a 10 × 10 mm baseplate. MNs were then immersed in an isopropyl alcohol bath to remove unpolymerized resin residues and cured in a UV-A heated chamber (Formlabs, UK). In total, nine samples were taken for each combination of curing temperature (35, 50, and 70 °C) and curing time (5, 20, and 60 min). Fracture tests were conducted using a hardness apparatus TB24 (Erweka, Germany). MNs were placed on the moving probe of the machine and compressed until fracture. The optimization of the SLA process parameters for improving the strength of MNs was performed using the Taguchi method. The design of experiments was carried out based on the Taguchi L9 orthogonal array. Experimental results showed that the curing temperature has a significant influence on MN strength improvements. Improvement of the MN strength can be achieved by increasing the curing temperature and curing time.
Collective cell migration is thought to be a dynamic and interactive behavior of cell cohorts that is essential for diverse physiological developments in living organisms. Recent studies revealed that the topographical properties of the environment regulate the migration modes of cell cohorts, such as diffusion versus contraction relaxation transport and the appearance of vortices in larger available space. However, conventional in vitro assays fail to observe changes in cell behavior in response to the structural changes. In this study, we developed a method to fabricate the flexible three-dimensional structures of capillary microtunnels to examine the behavior of vascular endothelial cells (ECs). Microtunnels with altering diameters were formed inside gelatin gel through spot heating a portion of gelatin by irradiating the µm-sized absorption at the tip of the microneedle with a focused permeable 1064 nm infrared laser. The ECs moved and spread two-dimensionally on the inner surface of the capillary microtunnels as a monolayer instead of filling the capillary. In contrast to the 3D straight topographical constraint, which exhibited width-dependent migration velocity, the leading ECs altered its migration velocity according to the change in the supply of cells behind the leading ECs, caused by their progression through the diameter-altering structure. Our findings provide insights into the collective migration modes inside 3D confinement structures, including their fluid-like behavior and the conservation of cell numbers.
The diagnosis of several diseases can be performed by analyzing the blood plasma of a patient. Despite extensive research work, there is still a need to improve current low-cost fabrication techniques and devices for the separation of plasma from blood cells. Microfluidic biomedical devices have great potential for that process. Hence, a microfluidic device made by micromilling and sealed with an oxygen plasma technique was tested by means of two different blood analogue fluids. The device has four microchannels with similar geometries but different channel depths. A high-speed video microscopy system was used for the visualization and acquisition of the flow of the analogue fluids throughout the microchannels of the device. Then, the separation of particles and plasma was evaluated with the ImageJ software by measuring and comparing the grey values at the entrance and the exit of the channel. The device showed a significant reduction of the amount of cells between the entrance and the exit of the microchannels. The depth of the channels and the size of the particles were not found to exert any major influence on the separation process. However, it was found that the flow rate affected the separation results, as the best results were obtained for a flow rate of 100 μL/min. Though these results are promising, further analyses and optimizations of microfluidic devices, as well as comparisons between devices sealed using different methods such as the solvent bonding technique, will be conducted in future works.
Janus micromotors are a unique class of materials whose surfaces have two or more distinct physical properties, allowing thus for two types of chemistry to occur simultaneously. Judicious design of the micromotor structure allows to incorporate different functionalities in a single unit to adapt the propulsion behaviour along with the incorporation of specific receptors for a myriad of applications. Herein we report the preparation of graphene oxide (GO)/PtNPs/Fe2O3 Janus micromotors for highly selective capture/inactivation of gram-positive bacteria units and biofilms. The strategy is based on the combination of a lanbiotic (Nisin) with Janus micromotors. Lanbiotics are peptides composed of methyllanthionine residues with a highly selective antimicrobial activity towards multidrug resistant bacteria. Nisin is a natural compound normally used for food preservation, which display specific antimicrobial activity towards gram-positive bacteria. Such peptide can bind to lipid II unit of the bacteria membranes, damaging its morphology and releasing its contents. The coating of micromotors with GO impart them with a Janus structure for the subsequent asymmetric assembly of catalytic (PtNPs) and magnetic (Fe2O3) engines and results in an active rough layer for a higher loading of Nisin via covalent interactions. The micromotors possess adaptative propulsion mechanisms, including catalytic mode (PtNPs) in peroxide solutions or magnetic actuation (fuel free) by the action of an external magnetic field. The enhanced movement and localized delivery of the micromotors (both in catalytic and magnetic actuated mode) results in a 2-fold increase of the capture/killing ability towards Staphylococcus Aureus bacteria in raw media (juice, serum and tap water samples), as compared with free Nisin and static counterparts. The micromotor strategy display also high selectivity towards such bacteria, as illustrated by the dramatically lower capture/killing ability towards gram-negative Escherichia Coli. Unlike previous micromotors based strategies, this approach displays higher selectivity towards a type of bacteria along with enhanced stability, prolonged use and adaptative propulsion modes, holding considerable promise to treat methicillin resistant antibiotic infections, for environmental remediation or food safety, among others applications.
Two-photon laser scanning microscope (TPLSM) provides outstanding optical three dimension section properties and it has been widely used in fundamental science and biomedical application. However, Current 3D two-photon fluorescence (TPF) imaging techniques usually overlook the spatiotemporal evolution of TPF ellipsoid along the axial direction, which might contain fine dynamical information of imaged targets. Here, we develop a spatiotemporal scanning technique and realize the measurement of spatiotemporal scanning of TPF ellipsoid with a semiconducting CsPbBr3 nanosheet. Results have shown that axial size of TPF ellipsoid present linear growth as a function of excitation fluence by using spatial scanning. Furthermore, we have observed that axial size of TPF ellipsoid exhibits inhomogeneous linear growth with time delay by introducing spatiotemporal scanning technique. We attribute this phenomenon to the fact that surface and bulk region of CsPbBr3 nanosheet have inhomogeneous timescale on TPF decay lifetime. Our results not only provide new insights for spatiotemporal resolving of TPF ellipsoid, but also helpful to promote the development of fluorescence lifetime microscopy technology.
