Micro and nanofluidics

Micro magnetofluidics

Work in the Nam-Trung Nguyen lab (NTNLab) examines a digital microfluidic platform that manipulates droplets on an open surface. Magnetic digital microfluidics utilizes magnetic forces for actuation and offers unique advantages compared to other digital microfluidic platforms. First, the magnetic particles used in magnetic digital microfluidics have multiple functions. In addition to serving as actuators, they also provide a functional solid substrate for molecule binding, which enables a wide range of applications in molecular diagnostics and immunodiagnostics. Second, magnetic digital microfluidics can be manually operated in a “power-free” manner, this allows for operation in low-resource environments for point-of-care.1

Paper-based microfluidics and sensors are attracting research attention. While many paper-based devices have been developed, few studies investigate paper actuators. To fulfil the requirements for the integration of both sensors and actuators into paper, work from NTNLab examines a unique platform utilising ferromagnetic particles for actuation and graphite for motion monitoring. Using an integrated mechanical sensing element removes the reliance on image processing for motion detection and allows real-time measurements of the dynamic response in paper-based actuators.2

The challenge in designing micromixers is to achieve fast and efficient mixing within a short residence time or in a short microchannel. NTNLab work examines a simple and low-cost micromixer using magnetofluidic actuation. The device takes advantage of magnetoconvective secondary flow, a bulk flow induced by an external magnetic field, for mixing. A superparamagnetic stream of diluted ferrofluid and a non-magnetic stream are introduced to a straight microchannel. A permanent magnet placed next to the microchannel induced a non-uniform magnetic field. The magnetic field gradient and the mismatch in magnetic susceptibility between the two streams create a body force, leading to rapid and efficient mixing.3

Meanwhile, ferrofluids offer promising advantages for heat transfer augmentation. NTNLab work shows heat transfer manipulation and control in a magnetofluidic device. The device consists of a circular chamber with a heat source on top next to a permanent magnet that creates a non-uniform magnetic field. Convective heat transfer has been evaluated and compared for: DI-water, ferrofluid, and ferrofluid under the magnetic field. Results indicate enhancement of convective heat transfer with the use of diluted ferrofluid as the working fluid.4 Further work examines the use of diluted ferrofluid and two arrays of permanent magnets for the size-selective concentration of non-magnetic particles. The micro magnetofluidic device consists of straight channels sandwiched between two arrays of permanent magnets. The permanent magnets create multiple capture zones with minimum magnetic field strength along the channel. The results could be used as a guide for the design of size sensitive separation devices for particle and cell based on negative magnetophoresis.5

NTNLab is undertaking modelling of a uniaxial single-sided magnetically actuated cell-stretching device. The numerical simulation of the actuation system consisting of a permanent magnet and an electromagnet. The magnetic flux density and magnetic force were verified experimentally over the range of superimposed magnetic flux density from 186 mT to 204 mT. 6 Research is also being undertaken on an electromagnetic cell-stretching device for mechanotransduction studies of olfactory ensheathing cells. Work in the Lab has seen the development of an electromagnetic cell stretching device based on a single sided uniaxial stretching approach to apply tensile strain to OECs in culture.7

Liquid marble-based digital microfluidics

A key research topic in the micro- and nanofluidics program is the examination of liquid-based mircofluidics, for example liquid marbles. A liquid marble is a liquid droplet coated with hydrophobic powder, enabling the marble to be manipulated like a soft solid. Such marbles have seen applications such as microbioreactors for three-dimensional cell cultures and have potential as a new platform for digital microfluidics. Research from the group seeks to investigate the functionality and application of liquid marble-based digital microfluidics.1 One of our earlier projects describes the protocols for the three-dimensional culturing of olfactory ensheathing cells (OECs). Transplantation of OECs is being trialled for repair of the paralysed spinal cord, with promising but variable results and thus the therapy needs improving. 2 We have also examined the use of a liquid marble containing ethanol to generate the solutocapillary effect. In this research, we derived the scaling laws relating the dynamic parameters of the motion to the physical properties of the system including the effective surface tension of the marble, the viscosity and the density of the supporting liquid, the coefficient of diffusion of the ethanol vapour, the geometrical parameters of the marble, the speed, the trajectory and the lifetime of the autonomous motion.3 In another project we investigated the magnetic actuation of floating liquid marbles filled with magnetic particles. The magnetic force and frictional force acting on the floating liquid marble determined the horizontal movement of the marble. By varying the magnetic flux density, flux density gradient, concentration of magnetic particles and speed of the marble, we could elucidate the relationship between the acting forces. We subsequently determined the suitable operating conditions for the actuation and derived the scaling laws for the actuation parameters.4, 5 In our most recent work in liquid marbles we mimic the hostile 3D environment to analyse the functional behaviour of the cells and to form the basis for cell-based therapy. We could show that OECs interact with debris and enhanced cellular aggregation to form a larger 3D spheroidal tissue.6

Microscale transport phenomena

Research from the NTNLab examines particle transport in microchannels that has been modelled using a fixed-grid method. The focus is on situations in which the particles are of comparable size to the microchannels. The particle affects the fluid flow field and vice versa. The method is undertaken utilising (1) flow around stationary cylinders, (2) flow around forced rotating cylinders, (3) flow around freely rotating circular cylinders, and (4) a circular cylinder settling under gravity. The method can be used to model particle transport in microchannels and particle separation process.1

Advancements in ultra-precision technologies and micromachining processes have resulted in the fabrication of well-defined nanochannels, which have applications in biomedical analysis, fuel cell, and water technologies. Understanding the characteristics of fluid transport at the nanoscale is critical as there are phenomena that have not yet been described by a complete theory. Experimental investigations provide interesting results that are unique at the nanoscale and require extensive studies to be fully understood. Work in the NTNLab seeks to understand transport in nanochannels from the different aspects of theory, experiment, fabrication and simulation.2

Concentration gradient generation in microfluidics is typically constrained by two conflicting mass transport requirements: short characteristic times (τ) allow for the precise temporal control of concentration gradients but at the expense of high flow rates and hence, high flow shear stresses (σ). To decouple the limitations of these parameters, the NTNLab is examining the use of stagnation flows to confine concentration gradients within large velocity gradients that surround the stagnation point. A modified cross-slot (MCS) device capable of feeding binary and combinational concentration sources in stagnation flows has been developed, showing that across the velocity well, source-sink pairs can form permanent concentration gradients.3

The NTNLab has demonstrated that a non-uniform magnetic field and diluted ferrofluid can improve mass transport of non-magnetic solutes in a microfluidic device. The platform could be used as a microfluidics-based gradient generator or micromixer.4

Droplet based microfluidics

Convective heat transfer in droplet-based microchannel heat sinks can be enhanced by the recirculating vortices due to the presence of interfaces. In rectangular microchannels, the three dimensional structures of the vortices and the ‘gutters’ (ie the space between the curved droplet interface and the corner of the microchannel) can significantly affect the heat transfer process. Numerical simulations of the heat transfer process are performed to study the three dimensional features in droplet-based microchannel heat sinks, with results showing that the ‘gutters’ can hinder the heat transfer process because of its parallel flow. On contrast, the recirculating flow in droplets and in slug regions between successive droplets can enhance the heat transfer by advecting hot fluid towards the center of the droplets/slugs and advecting fresh fluid towards the wall of the channel.1 Research from the NTNLab proposes to continuously generate droplets with programmable concentration using the ion concentration polarization (ICP) phenomenon. Via this method, our fabrication method has the advantages of simplicity, reliability, repeatability and low-cost. Sample droplets with up to 100-fold concentration were generated continuously with our device.2

Bioaffinity mass spectrometry screening is a novel approach using non-denaturing electrospray ionization (ESI) mass spectrometry (MS) in identifying drug leads. This technique can detect and preserve noncovalent protein-active drug ligand complexes under different physiological conditions. The screening challenge being the reduction of sample volume needed. The NTNLab demonstrates that analysis of samples can be performed using droplet-based microfluidics, with results showing that a MS instrument with a conventional ESI source can detect the samples and distinguish it with the separating oil phase.3

The NTNLab is committed to developing new micron-sized droplets. Delicate control of the droplet generation process is needed to address complex applications. At the liquid/liquid interface, an energy imbalance leads to instability and droplet breakup. Controlling the droplet generation process is a central topic of microfluidics.4 Work in the NTNLab presents state-of-the-art technologies to efficiently sort droplets. We classify the concepts according to the type of energy implemented into the system. Combining digital microfluidic devices allows for functional, flexible and powerful systems, covering specific technological areas and applications where electronics alone cannot compete or cannot offer an integrated chemical or biochemical functionality. Most powerful is the compatibility with digital electronics that allows for programmability and storage of droplets and droplet trains.5

Our work introduces an effective method to actively induce droplet generation using negative pressure. Droplets can be generated on demand using a series of periodic negative pressure pulses. Fluidic network models were developed using the analogy to electric networks to relate the pressure conditions for different flow regimes. Experimental results show that the droplet volume is correlated to the pressure ratio with a power law of 1.3.6

Automated droplet measurement (ADM) software has been developed based on OpenCV image processing library that has much higher throughput than currently available software. The process speed was found to be higher than the transfer speed even when visual feedback is enabled. Added to this, to shorten the total time taken on droplet measurement further, our Lab integrated newly developed ADM software and camera software development kit together in a new process flow. This was done by performing video transfer/streaming simultaneously with video processing. The total time for the droplet measurement using the integrated software was found significantly shorter than using the old process flow with DMV software.7

Micro optofluidics

For decades, microelectromechanical (MEMS) systems sensors have been intensively developed using various physical concepts, including piezoresistive, piezoelectric, and thermoresistive effects. The thermoresistive effect, which refers to the electrical resistance change with temperature variation, has many advantages in terms of simplicity in design and implementation. Based on this effect, various micro-sized thermal sensors, which can monitor temperature, flow and acceleration, have been successfully fabricated, thanks to the advancement in MEMS technologies.1

Research from the Nam-Trung Nguyen lab (NTNLab) examines the design and demonstration of an optofluidic in-plane bi-concave lens to perform both light focusing and diverging. With the concave lens hydrodynamically formed in a rectangular chamber with a liquid core cladding (L2) configuration. Our research has found that the focusing mode of the opto- fluidic bi-concave lens can be simply switched to diverging mode by stopping the pumping the liquid from core inlet. The previous cladding liquid (cinnamaldehyde) would join together in the chamber and become the core stream for the diverging mode. The auxiliary cladding liquid would change its function from avoiding light-scattering to becoming the cladding stream for the diverging mode. Combining the performance of focusing and diverging, the tunability of the focal length of the optofluidic lens and the width of the light beam can be greatly enhanced. This improvement of tunability will make this optofluidic bi-concave lens more adaptive to the lab-on-chip applications.2

NTNLab is also examining modelling and experimental results of a liquid-core liquid-cladding optofluidic lens under the combined effect of hydrodynamics and electro-osmosis. To allow the lens to be tuned by a voltage, the cladding fluids are electrically conducting, while the core fluid is non-conducting. Our results show that the interfaces between the cladding fluids and the core fluid have optically smooth arc shape. Under fixed cladding flow rates, the same voltage forms symmetric biconvex lens only. Different voltages can form biconvex lens, planoconvex lens, and meniscus lens.3

Integrating a flow cytometer into microfluidic networks helps to miniaturize the system and make it portable for field use with applications in environmental monitoring, industrial testing and biochemical studies. Integration of optical components, such as lenses, further improves the compactness. However, many current designs suffer from severe light scattering due to roughness of the solid-based lens interface. Our research examines a flow cytometer using an optofluidic lens to focus the light beam. Benefiting from the smooth liquid–liquid lens interface and the refractive-index matching liquid as cladding streams, a light beam can be well focused without scattering. The variations of the signal peak values are reduced, owing to the small beam width at the beam waist.4 We are also undertaking work on an optofluidic aperture stop formed by the liquid-core/liquid-cladding flow;5 and numerically and experimentally investigating and the design of an optofluidic in-plane bi-concave lens to perform both light focusing and diverging using the combined effect of pressure driven flow and electro-osmosis.6

Further work by the NTNLab illustrates the concept of liquid crystal based tunable optofluidic polarizer. Our research to date demonstrates the working principle, fabrication and characterization of a novel optofluidic tunable polarizer suitable for lab-on-a-chip applications. The concept and developed probe can find potential optics and lab-on-a chip applications.7

Lab-on-a-chip and point-of-care diagnostics

Rare cells are low-abundance cells in a much larger population of background cells. It is difficult to isolate and analyse rare cells because of their generally low selectivity and significant sample loss. Microfluidics provides robust solutions including apparent performance enhancements resulting in higher efficiencies and sensitivity levels. It also provides simpler handling of small sample volumes and multiplexing capabilities for high-throughput processing. The NTNLab continue to examine the design considerations of representative microfluidic devices for rare cell isolation and analysis.1

A system of multiple organs integrated on a single chip or human on a chip (HUC) has potential in drug discovery, and could overcome the limitations of animal models including cost and incompatibility with human physiology. The matching length scale of biological structures and micromachined components makes a microfluidic chip the ideal platform to investigate physiological events. The NTNLab continues to study the development of HUC, including the integration of cell culture on a chip to create an ethical human model and to provide insights into the sensitivity of different cell constructs on drugs.2

Understanding the process of fusion of olfactory ensheathing cell (OEC) spheroids will lead to improvement of cell transplantation therapies to repair spinal cord injuries. OECs are neuroglia cells that provide support and protection for olfactory sensory neurons in the peripheral nervous system (PNS). The NTNLab has developed a microfluidic device that enables injection and capture of spheroids of OECs.3

Piezoelectric thin films including zinc oxide and aluminium nitride are used in lab-on-chip applications such as biosensing, particle/cell concentrating, sorting/patterning, pumping, mixing, nebulisation and jetting. Integrated acoustic wave sensing/microfluidic devices have been fabricated by depositing these piezoelectric films onto substrates for making flexible devices, which have the potential to integrate disposable, or bendable/flexible lab-on-a-chip devices into various sensing and actuating applications. The NTNLab continues to engineer high performance piezoelectric thin films, with our research examining critical issues such as film deposition, MEMS processing techniques, control of deposition/processing parametres, film texture, doping, dispersion effects, film stress, multilayer design, electrode materials/designs and substrate selections.4

Current in vitro gut models lack physiological relevance, and various approaches have been taken to improve current cell culture models. For example, mimicking the 3D tissue structure or fluidic environment has shown improved physiological function of gut cells. The NTNLab’s research has incorporated a collagen scaffold that mimics the human intestinal villi into a microfluidic device, providing cells with both 3D tissue structure and fluidic shear. Our research suggests the combination of fluidic stimulus and 3D structure induces improvement in gut functions.5

Significant progress has been made in the fabrication and characterisation of MEMS thermal sensors that use the thermoresistive effect in metals such as platinum and semiconductors including silicon and polysilicon. Drawbacks include cost and the low capability to work in high temperature environments. Research in alternative thermal sensing materials with high thermoresistive sensitivity is being investigated by the NTNLab, as is proper packaging for thermal sensors as thermal expansion at high temperatures can cause cracking in devices. An alternative trend is low-cost materials for thermal sensors, which can be processed using cleanroom-free facilities and user-friendly techniques. For example, the thermoresistive effect in pencil graphite has been intensively investigated, and a proof of concept of thermal flow sensors has been successfully demonstrated.6