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  • Open access
  • 111 Reads
Lipid-based nanoparticle production in Micromixers

Lipid-based nanoparticles have demonstrated to be a versatile vehicle for drugs, genetic material, and labels. These particles are often made of biocompatible and biodegradable materials, enabling a safe interaction with biological systems. The importance of this type of delivery vehicle has been shown recently, as the two leading vaccines are based on lipid-nanoparticles encapsulating mRNA.

Passive micromixers produce lipid nanoparticles in a reproducible and controllable way. However, micromixers suffered at the beginning of low production rate, and complicated designs which were difficult to produce and prone to clogging. In recent years, the exploration of different mixing strategies based on the use of curvilinear paths to induce centripetal forces and vortex formation at high speeds as well as the increase of the microchannel cross-sectional area while keeping laminar flow regimes has led to designs capable of producing lipid-based nanoparticles on an industrial-scale.

However, there are still challenges in the field which include the removal or substitution of the organic solvents that still need to be addressed.

In this presentation, we introduce a general overview of lipid nanoparticle or liposome production in micromixers, the principles of mixing using curvilinear paths, the key variables controlling lipid-based nanoparticle physicochemical characteristics and approaches that help to substitute toxic solvent residues.

  • Open access
  • 207 Reads
Antibody Immobilization in ZnO-Thin film transistors for low-cost biosensors applications

The antibody immobilization with low-cost materials and label-free methods are a challenge for the fabrication of biosensor devices. In this work, it was developed a strategy for antibody immobilization on ZnO TFTs over polyethylene terephthalate (PET) as a recyclable plastic substrate. In a first approach we performed a detection of 1x108 enteropathogenic E. coli UFC/mL used as our testing model. Antibodies were biofunctionalized using a label-free strategy for bacterial detection. This strategy was able to couple the physics of transistors, the film deposition at low temperature and the binding of the biological recognition element (antibody) without affecting the functionality of the device. Fourier Infrared spectroscopy (FTIR) is a non-destructive technique used for monitoring the complete process, showing the characteristic signals (amide I, II and S-S) related to the antibody immobilization on ZnO-TFTs. Moreover, the transfer characteristics allowed us to observe the device before and after the immobilization and the changes in the shift of the threshold voltage Vt. The use of a recyclable plastic substrate PET enables the compatibility with flexible electronics that could contribute for a low-cost biosensor useful in rural communities that do not have the necessary infrastructure and trained personnel for pathogenic bacterial detection in food or water. The development of this technology has the versatility to be extrapolated to different testing models, allowing the early detection of emerging diseases (bacterial or viral), and also it provides the opportunity to end-users for self-testing.

  • Open access
  • 173 Reads
Droplet formation in a cross-junction microfluidic channel with non-Newtonian dispersed phase

Microfluidics enables generating series of isolated droplets for high-throughput screening. As many biological/chemical solutions are of shear thinning non-Newtonian nature [1,2], 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 interFoam solver and volume of fluid (VOF) method [3].

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 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 [4] : (a) breakup of the dispersed phase thread occurred at 0.0365, 0.0430, 0.0440, 0.0450 s; (b) the dimensionless width of the thread at the main channel entrance increased from 0 to 0.066, 0.096, 0.16; and (c) the dimensionless droplet diameter decreased from 0.76 to 0.72, 0.68, 0.67, respectively. Our next plan is to study effect of shear-thinning behaviour on droplet generation in different Ca and flow-rate ratios.


  1. Eun, Y.; Utada, A.S.; Copeland, M.F.; Takeuchi, S.; Weibel, D.B. Encapsulating Bacteria in Agarose Microparticles Using Microfluidics for High-Throughput Cell Analysis and Isolation. ACS Chem. Biol. 2011, 6, 260–266, doi:10.1021/cb100336p.
  2. Khater, A.; Khater, A.; Abdelrehim, O.; Mohammadi, M.; Mohammadi, M.; Mohammadi, M.; Azarmanesh, M.; Azarmanesh, M.; Janmaleki, M.; Salahandish, R.; et al. Picoliter agar droplet breakup in microfluidics meets microbiology application: Numerical and experimental approaches. Lab Chip 2020, 20, 2175–2187, doi:10.1039/d0lc00300j.
  3. Chen, Q.; Li, J.; Song, Y.; Christopher, D.M.; Li, X. Modeling of Newtonian droplet formation in power-law non-Newtonian fluids in a flow-focusing device. Heat Mass Transf. 2020, 56, 2711–2723, doi:10.1007/s00231-020-02899-6.
  4. Taassob, A.; Manshadi, M.K.D.; Bordbar, A.; Kamali, R. Monodisperse non-Newtonian micro-droplet generation in a co-flow device. J. Brazilian Soc. Mech. Sci. Eng. 2017, 39, 2013–2021, doi:10.1007/s40430-016-0699-z.
  • Open access
  • 81 Reads
Experimental studies of the sedimentation, stability and thermal conductivity of two different nanofluids

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 Al2O3nanoparticles (NPs) with 50 nm of diameter and the second is a novel NF formed by poly (acrylic acid)-coated iron oxide NPs (Fe3O4@PAA) with ~10 nm of 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.

  • Open access
  • 90 Reads
Elasto-Magnetic Pumps Integrated within Microfluidic Devices

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 utilised 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 which 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 3-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 resultant flow direction can be reversed by adjusting the frequency of the driving field. The device is 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 more portable applications.

  • Open access
  • 127 Reads
Optimization of Manufacturing Parameters of 3D Printed Solid Microneedles for Transdermal Drug Delivery

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 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°C, 50°C, and 70°C) and curing time (5 min, 20 min, 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.

  • Open access
  • 138 Reads
Purification of biodiesel produced by lipase catalysed transesterification by two-phase systems based on deep eutectic solvents in a microextractor: Selection of solvents and process optimization

The most important and the most used process of biodiesel synthesis is transesterification. The main byproduct formed in the biodiesel synthesis by transesterification is glycerol. Biodiesel produced by transesterification is not suitable for application in engines since it contains soap (if biodiesel is produced by chemical catalysis), traces of the catalyst, methanol, metals, water, oil, and glycerides. All those impurities have to be removed in order to reach the standards (ASTM D6751 and EN 14214). The most dominant industrial method for biodiesel purification is wet washing, which generates up to 10 L of wastewater per 1 L of purified biodiesel. Therefore, cheaper and more efficient solutions for biodiesel purification should be found. Deep eutectic solvents (DESs) have been already demonstrated as a viable options in biodiesel purification. DESs, a mixture of two or more components with a lower melting point than each individual component, are considered less toxic to the environment, non-volatile, biodegradable, more stable, in other words, they are economically and environmentally friendly in comparison with organic solvents.

In this study, purification of biodiesel produced by lipase catalysed transesterification by DESs was performed by two-phase liquid extraction in a microextractor. A total of 13 different DESs were synthesized and used for biodiesel purification in order to find the one that provides the best glycerol extraction efficiency. After initial screening, three DESs were selected and used for the optimization of process conditions for extraction performed in a microsystem. A three-level-four-factor Box-Behnken experimental design was employed to define the optimal process conditions (biodiesel-DES mass ratio, temperature, residence time). At optimal process conditions, the glycerol content in biodiesel was reduced below 0.02% (w/w) which is the value specified by standards (ASTM D6751 and EN 14214).

  • Open access
  • 93 Reads
Manipulation of Microrobots using Chladni Plates and Multimode Membrane Resonators

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.

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.

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: (1) macroscale manipulation with a Chladni plate in air and (2) 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.

  • Open access
  • 63 Reads
Dynamic characterization of biosensing MEMS cantilevers with different position of the driving electrode - vacuum response versus ambient conditions

The influence of the driving electrode positions on the dynamic response of polysilicon MEMS resonators used in biosensing applications is studied as a function of the operating conditions (vacuum versus free-air operating mode). The scope of this research work is orientated to identify the effect of driving electrode position on the dynamic response of sensing MEMS used in bio-mass detection. The mass-deposition detection is based on the change in the resonant frequency of vibrating elements considering a biological detection film deposited on the oscillating structure. The operating conditions, such as medium pressure, change the behavior of the dynamic response including the resonant frequency, the amplitude, and the velocity of oscillations as well as the quality factor and the loss of energy. The change in the dynamic response of the investigated MEMS cantilevers as function of the lower electrode position and operating conditions is evaluated using a Polytec Laser Vibrometer. The decrease in the amplitude and velocity of the oscillations if the lower electrode is moved from the beam free-end toward the beam anchor is experimentally monitored. The changes in the response of samples in vacuum are slightly influenced by the electrode position compared with the response of the same sample in ambient conditions. Moreover, the effect of oscillating modes (1st, 2nd and 3rd modes) is taken into consideration to improve the dynamical detection of the investigated samples. The obtained results indicate that, different responses of MEMS resonators can be achieved if the position of the driving electrode is moved from the cantilever free-end toward the anchor. Indeed, the resonator stiffness, velocity and amplitude of oscillations are significantly modified for samples oscillating in ambient conditions for biological detection compared with their response in vacuum.

  • Open access
  • 71 Reads
Fiber optic sensor for detecting neoplastic lesions in biological tissues - a preliminary study

Tissues affected by neoplastic lesions differ from healthy tissues in terms of functionality and anatomy. These changes affect light propagation in tissue, therefore modifying the refractive index, as well as scattering and absorption coefficients. The primary purpose of the research was to create a system to detect local changes in the refractive index using a fiber optic sensor. A prototype of a micromachine for biomedical applications has been developed. The measurements were performed using the low-coherence interferometry method, i.e. a measurement technique based on the phenomenon of interference of light waves from a broadband light source. The constructed optical system uses a light source with a central wavelength of 1550 nm, a spectrum analyser, a fiber optic sensor operating on the basis of a Fabry-Perot interferometer and a silver mirror acting as a reflective layer. Measurements of the interference spectrum of reference oils, used for calibration due to the high stability of their parameters, were performed. It has been shown that the developed fiber optic sensor is able to detect changes in the refractive index based on the shift in the position of the central peak in the interference spectrum. It is also sensitive to changes of the absorption coefficient.

1. Szczerska, M. Response of a New Low-Coherence Fabry-Perot Sensor to Hematocrit Levels in Human Blood. Sensors, 14(4), 6965-6976, (2014).
2. Giannios, P., Toutouzas, K., Matiatou, M. et al. Visible to near-infrared refractive properties of freshly-excised human-liver tissues: marking hepatic malignancies. Sci Rep 6, 27910 (2016), doi: 10.1038/srep27910.