Microfluidically fabricated pH-responsive anionic amphiphilic microgels for drug release

© 2016 The Royal Society of Chemistry. Amphiphilic microgels of different composition based on the hydrophilic, pH-responsive acrylic acid (AA) and the hydrophobic, non-ionic n-butyl acrylate (BuA) were synthesised using a lab-on-a-chip device. Hydrophobic droplets were generated via a microfluidic platform that contained a protected form of AA, BuA, the hydrophobic crosslinker, ethylene glycol dimethacrylate (EGDMA), and a free radical initiator in an organic solvent. These hydrophobic droplets were photopolymerised within the microfluidic channels and subsequently hydrolysed, enabling an integrated platform for the rapid, automated, and in situ production of anionic amphiphilic microgels. The amphiphilic microgels did not feature the conventional core-shell structure but were instead based on random amphiphilic copolymers of AA and BuA and hydrophobic crosslinks. Due to their amphiphilic nature they were able to encapsulate and deliver both hydrophobic and hydrophilic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the surrounding aqueous solution and the hydrophobic content of the microgels

Tailoring pH-responsive acrylic acid microgels with hydrophobic crosslinks for drug release

Amphiphilic microgels based on the hydrophilic acrylic acid (AA) and hydrophobic crosslinks of different compositions were synthesised using a lab-on-a-chip device. The microgels were formed by polymerising hydrophobic droplets. The droplets were generated via a microfluidic platform and contained a protected form of AA, a hydrophobic crosslinker (ethylene glycol dimethacrylate, EGDMA) and a free radical initiator in an organic solvent. Following photopolymerisation and subsequent hydrolysis, AA based microgels of amphiphilic nature were produced and it was demonstrated that they can successfully deliver both hydrophilic as well as hydrophobic moieties. The model drug delivery and the swelling ability of the microgels were influenced by the pH of the aqueous solution as well as the crosslinking density and hydrophobic content of the microgels

Magnetic particle plug-based assays for biomarker analysis

Conventional immunoassays offer selective and quantitative detection of a number of biomarkers, but are laborious and time-consuming. Magnetic particle-based assays allow easy and rapid selection of analytes, but still suffer from the requirement of tedious multiple reaction and washing steps. Here, we demonstrate the trapping of functionalised magnetic particles within a microchannel for performing rapid immunoassays by flushing consecutive reagent and washing solutions over the trapped particle plug. Three main studies were performed to investigate the potential of the platform for quantitative analysis of biomarkers: (i) a streptavidin-biotin binding assay; (ii) a sandwich assay of the inflammation biomarker, C-reactive protein (CRP); and (iii) detection of the steroid hormone, progesterone (P4), towards a competitive assay. Quantitative analysis with low limits of detection was demonstrated with streptavidin-biotin, while the CRP and P4 assays exhibited the ability to detect clinically relevant analytes, and all assays were completed in only 15 min. These preliminary results show the great potential of the platform for performing rapid, low volume magnetic particle plug-based assays of a range of clinical biomarkers via an exceedingly simple technique

On-chip determination of C-reactive protein using magnetic particles in continuous flow

We demonstrate the application of a multilaminar flow platform, in which functionalized magnetic particles are deflected through alternating laminar flow streams of reagents and washing solutions via an external magnet, for the rapid detection of the inflammatory biomarker, C-reactive protein (CRP). The two-step sandwich immunoassay was accomplished in less than 60 s, a vast improvement on the 80−300 min time frame required for enzyme-linked immunosorbent assays (ELISA) and the 50 min necessary for off-chip magnetic particle-based assays. The combination of continuous flow and a stationary magnet enables a degree of autonomy in the system, while a detection limit of 0.87 μg mL−1 makes it suitable for the determination of CRP concentrations in clinical diagnostics. Its applicability was further proven by assaying real human serum samples and comparing those results to values obtained using standard ELISA tests

Generation and manipulation of magnetic droplets

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.The continuous flow generation and downstream manipulation of magnetic droplets inside a microfluidic device was investigated. Magnetic droplets were generated from aqueous ferrofluids in organic oil phase using T-junction and flow-focusing geometries in glass microfluidic devices. Due to the hydrophilic nature of glass surfaces, it was necessary to apply a hydrophobic coating in the form fluorocarbons. The size of the magnetic droplets and distance between them were controlled by adjusting the relative flow velocities of ferrofluid and oil carrier liquid. Two modes of droplet manipulation were investigated by placing small permanent magnets in the vicinity of the microfluidic channels: (i) droplet deflection across a flow chamber which could be used for sorting of droplets based on the magnetic field applied and (ii) droplet splitting at a branching junction resulting in two daughter droplets of high and low magnetite content.This study is funded by The University of Kuwait

The generation of multi-laminar reagent streams for rapid, sequential (bio)chemical reactions on magnetic particles in a continuous flow microreactor

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.We demonstrate a versatile microfluidic system for performing rapid, consecutive (bio)chemical reactions in continuous flow. Surface-functionalised magnetic microparticles are introduced into a chamber and pulled, via a magnet, across a series of laminar flow streams containing different reagents, thus performing multiple sequential reactions on the particles’ surface. Such a continuous flow method eliminates many of the inefficiencies associated with batch techniques, such as the time-consuming, laborious sequential reaction and washing steps, to yield a system that can perform analyses far more rapidly and with less reagent volume than conventional methods. This innovative device has been applied to a two-reaction step mouse IgG sandwich immunoassay and one- and two-reaction step DNA hybridisation assays, all of which were completed within one minute. These results pave the way for a multi-purpose microreactor that can perform a variety of analytical and synthetic processes.This study is funded by the Engineering and Physical Sciences Research Council (EPSRC)

Artificial leaf device for hydrogen generation from immobilised C. reinhardtii microalgae

We developed a fully biomimetic leaf-like device for hydrogen production which allows incorporated fabric-immobilised microalgae culture to be simultaneously hydrated with media and harvested from the produced hydrogen in a continuous flow regime without the need to replace the algal culture. Our leaf device produces hydrogen by direct photolysis of water resulting from redirecting the photosynthetic pathways in immobilised microalgae due to the lack of oxygen. In contrast to the many other reports in the literature on batch photobioreactors producing hydrogen from suspension culture of microalgae, we present the first report where this is done in a continuous manner from a fabric-immobilised microalgae culture. The reported artificial leaf device maximises the sunlight energy utilisation per gram of algae and can be upscaled cheaply and easily to cover large areas. We compared the production of hydrogen from both immobilised and suspended cultures of C. reinhardtii microalgae under sulphur, phosphorus and oxygen deprived conditions. The viability and potential of this approach is clearly demonstrated. Even though this is a first prototype, the hydrogen yield of our artificial leaf device is twenty times higher per gram of algae than in previously the reported batch reactors. Such leaf-like devices could potentially be made from flexible plastic sheets and installed on roofs and other sun-exposed surfaces that are inaccessible by photovoltaic cells. The ability to continuously produce inexpensive hydrogen by positioning inexpensive sheets onto any surface could have an enormous importance in the field of biofuels. The proposed new concept can provide a cleaner and very inexpensive way of bio-hydrogen generation by flexible sheet-like devices

Diamagnetic repulsion of particles for multilaminar flow assays

© The Royal Society of Chemistry. We demonstrate diamagnetic repulsion forces for performing continuous multilaminar flow assays on particles based on their intrinsic properties and with a simple setup. The platform could be applied to sandwich assays on polystyrene particles, and to cell-based assays via their suspension in biologically benign magnetic media

Temperature-based tuning of magnetic particle separation by on-chip free-flow magnetophoresis

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Free-flow magnetophoresis provides a fast and efficient means of continuous flow magnetic separation for the detection of biological analytes, due to the wide variety of magnetic particle surface properties available for binding specific targets. Here, we investigate the effect of temperature changes on the deflection behaviour of magnetic particles in a microfluidic magnetophoresis separation chamber. It was found that the extent of deflection was greatly increased at higher temperatures due to decreased solution viscosity and thus reduced resistance against particle motion. This concept was used to improve the resolution of the separation of 2.8 μm and 1 μm diameter magnetic particles. Hence, controlling the temperature of the separation system provides a simple but highly effective means of enhancing magnetic separation efficiency. This concept could also be applied to the temperature-based tuning of microparticle trajectories in many others types of continuous flow processes, such as those using optical, electrical or acoustic forces.This study is funded by the Engineering and Physical Sciences Research Council (EPSRC)

Novel Microgels Fabricated On Microfluidic Devices

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Microgels are micrometer sized particles consisting of a polymer network that show potential for the delivery of both hydrophilic and hydrophobic drugs. Microfluidic devices provide an excellent format for the generation of monodispersed droplets due to the precise manipulation of fluids and flow rates within the microchannels. Microfluidic droplet generation chips were therefore designed using T-junction and flow focusing geometries in glass. For microgel synthesis, monomers, crosslinker and initiator were added to the dispersed phase and water was used as the continuous phase. Controlled formation of monodisperse droplets was achieved with both geometries and droplets were collected off-chip for photopolymerisation. Three types of microgel were formed using this setup: poly(ethylene glycol) diacrylate, poly(propylene glycol) diacrylate, and tetrahydropyran acrylate - ethylene glycol dimethacrylate (THPA-EGDMA) microgels. THPA is a novel material for microgels that can be turned from hydrophobic to amphiphilic by hydrolysation. THPA-EGDMA microgels in particular demonstrated a strong response to pH changes due to the build-up of electrostatic force under high pH, showing potential for the encapsulation and release of drugs