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. 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. 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. 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. 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.

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. 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.