I am currently a researcher at the University of Leeds, working on microfluidic platforms for ice nucleation studies. I obtained a MChem degree (2007) and a PhD (2011) in analytical chemistry from the University of Hull (UK). I also worked as a post doc at KIST Europe (Germany) from 2011-2012 on the development of detection systems for capillary electrophoresis. I was a postdoc on a project involving miniaturised quality control testing in PET radiotracer production from 2012-2016 (Hull). Phone: +44 (0) 113 3435605 Address: School of Earth and Environment University of Leeds Woodhouse Lane Leeds LS2 9JT UK
Journal of Polymer Science, Part A: Polymer Chemistry, 2018
Cationic, amphiphilic microgels of differing compositions based on hydrophilic, pH, and thermores... more Cationic, amphiphilic microgels of differing compositions based on hydrophilic, pH, and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and hydropho-bic, nonionic n-butyl acrylate (BuA) are synthesized using a lab-on-a-chip device. Hydrophobic oil-in-water (o/w) droplets are generated via a microfluidic platform, with the dispersed (droplet) phase containing the DMAEMA and BuA, alongside the hydrophobic cross-linker, ethylene glycol dimethacrylate, and a free radical initiator in an organic solvent. Finally, the hydrophobic droplets are photopolymerized via a UV light source as they traverse the microfluidic channel to produce the cationic amphiphilic microgels. This platform enables the rapid, automated, and in situ production of amphiphilic micro-gels, which do not match the core-shell structure of conventionally prepared microgels but are instead based on random amphiphilic copolymers of DMAEMA and BuA between the hydrophobic cross-links. The microgels are characterized in terms of their swelling and encapsulation abilities, which are found to be influenced by both the pH response and the hydro-phobic content of the microgels.
Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer ... more Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer (LbL) deposition of PE layers of alternating charge on sacrificial template microparticles, which usually requires multiple incubation and washing steps that render the process repetitive and time-consuming. Here, ferrofluid droplets were explored for this purpose as an elegant alternative of templates that can be easily manipulated via an external magnetic field, and require only a simple microfluidic chip design and setup. Glass microfluidic devices featuring T-junctions or flow focusing junctions for the generation of oil-based ferrofluid droplets in an aqueous continuous phase were investigated. Droplet size was controlled by the microfluidic channel dimensions as well as the flow rates of the ferrofluid and aqueous phases. The generated droplets were stabilised by a surface active polymer, polyvinylpyrrolidone (PVP), and then guided into a chamber featuring alternating, co-laminar PE solutions and wash streams, and deflected across them by means of an external permanent magnet. The extent of droplet deflection was tailored by the flow rates, the concentration of magnetic nanoparticles in the droplets, and the magnetic field strength. PVP-coated ferrofluid droplets were deflected through solutions of polyelectrolyte and washing streams using several iterations of multilaminar flow designs. This culminated in an innovative “Snakes-and-Ladders” inspired microfluidic chip design that overcame various issues of the previous iterations for the deposition of layers of anionic poly(sodium-4-styrene sulfonate) (PSS) and cationic poly(fluorescein isothiocyanate allylamine hydrochloride) (PAH-FITC) onto the droplets. The presented method demonstrates a simple and rapid process for PE layer deposition in <30 seconds, and opens the way towards rapid layer-by-layer assembly of PE microcapsules for drug delivery applications.
A new approach for high voltage capillary electrophoresis (CE) is proposed, which replaces the st... more A new approach for high voltage capillary electrophoresis (CE) is proposed, which replaces the standard high voltage power supply with a Van de Graaff generator, a low current power source. Because the Van de Graaff generator is a current-limited source (10 μA), potentials exceeding 100 kV can be generated for CE when the electrical resistance of the capillary is maximized. This was achieved by decreasing the capillary diameter and reducing the buffer ionic strength. Using 2 mM borate buffer and a 5 μm i.d. capillary, fluorescently labeled amino acids were separated with efficiencies up to 3.5 million plates; a 5.7 fold improvement in separation efficiency compared to a normal power supply (NPS) typically used in CE. This separation efficiency was realized using a simple set-up without significant Joule heating, making the Van de Graaff generator a promising alternative for applying the high potentials required for enhancing resolution in the separation and analysis of highly complex samples, for example mixtures of glycans.
Despite recent advances in microfluidic-based integrated diagnostic systems, the sample introduct... more Despite recent advances in microfluidic-based integrated diagnostic systems, the sample introduction interface, especially with regards to large volume samples, has often been neglected. We present a sample introduction interface that allows direct on-chip processing of crude stool samples for the detection of Helicobacter pylori (H. pylori). The principle of IFAST (immiscible filtration assisted by surface tension) was adapted to include a large volume sample chamber with a septum-based interface for stool sample introduction. Solid chaotropic salt and dry superparamagnetic particles (PMPs) could be stored on-chip and reconstituted upon sample addition, simplifying the process of release of DNA from H. pylori cells and its binding to the PMPs. Finally, the PMPs were pulled via a magnet through a washing chamber containing an immiscible oil solution and into an elution chamber where the DNA was released into aqueous media for subsequent analysis. The entire process required only 7 min while enabling a 40-fold reduction in working volume from crude biological samples. The combination of a real-world interface and rapid DNA extraction offers the potential for the methodology to be used in point-of-care (POC) devices.
Conventional immunoassays offer selective and quantitative detection of a number of biomarkers, b... more 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.
Amphiphilic microgels of different composition based on the hydrophilic, pH-responsive acrylic ac... more 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.
We present a simple microfluidic system for rapid screening of Escherichia coli (E. coli) O157:H7... more We present a simple microfluidic system for rapid screening of Escherichia coli (E. coli) O157:H7 employing the specificity of immunomagnetic separation (IMS) via immiscible filtration assisted by surface tension (IFAST), and the sensitivity of the subsequent adenosine triphosphate (ATP) assay by the bioluminescence luciferin/ luciferase reaction. The developed device was capable of detecting E. coli O157:H7 from just 6 colony forming units (CFU) in 1 mL spiked buffer within 20 min. When tested with wastewater discharged effluent samples, without pre-concentration, the device demonstrated the ability to detect 10 4 CFU per mL seeded; suggesting great potential for point-of-need microbiological water quality monitoring .
The ability to detect radiation in microfluidic devices is important for the on-chip analysis of ... more The ability to detect radiation in microfluidic devices is important for the on-chip analysis of radiopharmaceuticals, but previously reported systems have largely suffered from various limitations including cost, complexity of fabrication, and insufficient sensitivity and/or speed. Here, we present the use of sensitive, low cost, small-sized, commercially available silicon photomultipliers (SiPMs) for the detection of radioactivity inside microfluidic channels fabricated from a range of conventional microfluidic chip substrates. We demonstrate the effects of chip material and thickness on the detection of the positron-emitting isotope, [(18)F]fluoride, and find that, while the SiPMs are light sensors, they are able to detect radiation even through opaque chip materials via direct positron and gamma (γ) ray interaction. Finally, we employed the SiPM platform for analysis of the PET (positron emission tomography) radiotracers 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [(68)Ga]gallium-citrate, and highlight the ability to detect the γ ray emitting SPECT (single photon emission computed tomography) radiotracer, [99mTc]pertechnetate.
We demonstrate the use of the miniaturised Medipix positron sensor for detection of the clinical ... more We demonstrate the use of the miniaturised Medipix positron sensor for detection of the clinical PET radiotracer, [68Ga]gallium-citrate, on a silica-based monolith, towards microfluidic quality control. The system achieved a far superior signal-to-noise ratio compared to conventional sodium iodide-based radio-HPLC detection and allowed real-time visualisation of positrons in the monolith.
The ability to engage and inspire younger generations in novel areas of science is important for ... more The ability to engage and inspire younger generations in novel areas of science is important for bringing new researchers into a burgeoning field, such as lab-on-a-chip. We recently held a lab-on-a-chip workshop for secondary school students, for which we developed a number of hands-on activities that explained various aspects of microfluidic technology, including fabrication (milling and moulding of microfluidic devices, and wax printing of microfluidic paper-based analytical devices, so-called μPADs), flow regimes (gradient formation via diffusive mixing), and applications (tissue analysis and μPADs). Questionnaires completed by the students indicated that they found the workshop both interesting and informative, with all activities proving successful, while providing feedback that could be incorporated into later iterations of the event.
We demonstrate diamagnetic repulsion forces for performing continuous multilaminar flow assays on... more 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.
Supplementary Information for "On-chip determination of C-reactive protein using magnetic particl... more Supplementary Information for "On-chip determination of C-reactive protein using magnetic particles in continuous flow"
Amphiphilic microgels based on the hydrophilic acrylic acid (AA) and hydrophobic crosslinks of di... more 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.
We demonstrate the application of a multilaminar flow platform, in which functionalized magnetic ... more 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.
Electronic supplementary information for "Radiochemistry on chip: towards dose-on-demand synthesi... more Electronic supplementary information for "Radiochemistry on chip: towards dose-on-demand synthesis of PET radiopharmaceuticals"
We demonstrate the application of magnetic forces for the simultaneous trapping of two types of p... more We demonstrate the application of magnetic forces for the simultaneous trapping of two types of particles, magnetic and diamagnetic, via a single set of magnets. Furthermore, we show how this simple setup can be employed for performing assays with a negative control, or for achieving multiple simultaneous analyses.
Science and Technology of Advanced Materials, 2009
We explore the potential of a microfluidic continuous flow particle separation system based on th... more We explore the potential of a microfluidic continuous flow particle separation system based on the repulsion of diamagnetic materials from a high magnetic field. Diamagnetic polystyrene particles in paramagnetic manganese (II) chloride solution were pumped into a microfluidic chamber and their deflection behaviour in a high magnetic field applied by a superconducting magnet was investigated. Two particle sizes (5 and 10 μm) were examined in two concentrations of MnCl2 (6 and 10%). The larger particles were repelled to a greater extent than the smaller ones, and the effect was greatly enhanced when the particles were suspended in a higher concentration of MnCl2. These findings indicate that the system could be viable for the separation of materials of differing size and/or diamagnetic susceptibility, and as such could be suitable for the separation and sorting of small biological species for subsequent studies.
Superconducting magnets enable the study of high magnetic fields on materials and objects, for ex... more Superconducting magnets enable the study of high magnetic fields on materials and objects, for example in material synthesis, self-assembly or levitation experiments. The setups employed often lack in precise spatial control of the object of interest within the bore of the magnet. Microfluidic technology enables accurate manipulation of fluidic surroundings and we have investigated the integration of microfluidic devices into superconducting magnets to enable controlled studies of objects in high magnetic fields. Polymeric microparticles similar in size to biological cells were manipulated via diamagnetic repulsion. The particles were suspended in an aqueous paramagnetic medium of manganese (II) chloride and pumped into a microfluidic chip, where they were repelled in continuous flow by the high magnetic field. The extent of deflection was studied as a function of increasing (1) particle size, (2) paramagnetic salt concentration, and (3) magnetic field strength. Optimizing these parameters allowed for the spatial separation of two particle populations via on-chip free-flow diamagnetophoresis. Finally, preliminary findings on the repulsion of air bubbles are shown.
We demonstrate a rapid method of coating a layer of polymer onto magnetically modified yeast cell... more We demonstrate a rapid method of coating a layer of polymer onto magnetically modified yeast cells, so-called “cyborg cells”, in continuous flow within a microfluidic chamber. Laminar flow streams of polyelectrolyte and washing buffers were generated across the chamber, and the magnetic cells were deflected sequentially through the co-flowing streams via an external magnet, allowing polyelectrolyte deposition onto the cells immediately followed by the washing step, all in less than 90 s. This simple deposition technique shows promise for the functionalization of such cyborg cells for applications including bioelectronics, bioanalysis, and toxicity screening, while the addition of more reagent streams would enable the fabrication of multilayered capsules.
The continuous flow focussing and manipulation of particles and cells are important factors in mi... more The continuous flow focussing and manipulation of particles and cells are important factors in microfluidic applications for performing accurate and reproducible procedures downstream. Many particle focussing methods require complex setups or channel designs that can limit the process and its applications. Here, we present diamagnetic repulsion as a simple means of focussing objects in continuous flow, based only on their intrinsic properties without the requirement of any label. Diamagnetic polystyrene particles were suspended in a paramagnetic medium and pumped through a capillary between a pair of permanent magnets, whereupon the particles were repelled by each magnet into the central axis of the capillary, thus achieving focussing. By investigating this effect, we found that the focussing was greatly enhanced with (i) increased magnetic susceptibility of the medium, (ii) reduced flow rate of the suspension, (iii) increased particle size, and (iv) increased residence time in the magnetic field. Furthermore, we applied diamagnetic repulsion to the flow focussing of living, label-free HaCaT cells.
Journal of Polymer Science, Part A: Polymer Chemistry, 2018
Cationic, amphiphilic microgels of differing compositions based on hydrophilic, pH, and thermores... more Cationic, amphiphilic microgels of differing compositions based on hydrophilic, pH, and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and hydropho-bic, nonionic n-butyl acrylate (BuA) are synthesized using a lab-on-a-chip device. Hydrophobic oil-in-water (o/w) droplets are generated via a microfluidic platform, with the dispersed (droplet) phase containing the DMAEMA and BuA, alongside the hydrophobic cross-linker, ethylene glycol dimethacrylate, and a free radical initiator in an organic solvent. Finally, the hydrophobic droplets are photopolymerized via a UV light source as they traverse the microfluidic channel to produce the cationic amphiphilic microgels. This platform enables the rapid, automated, and in situ production of amphiphilic micro-gels, which do not match the core-shell structure of conventionally prepared microgels but are instead based on random amphiphilic copolymers of DMAEMA and BuA between the hydrophobic cross-links. The microgels are characterized in terms of their swelling and encapsulation abilities, which are found to be influenced by both the pH response and the hydro-phobic content of the microgels.
Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer ... more Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer (LbL) deposition of PE layers of alternating charge on sacrificial template microparticles, which usually requires multiple incubation and washing steps that render the process repetitive and time-consuming. Here, ferrofluid droplets were explored for this purpose as an elegant alternative of templates that can be easily manipulated via an external magnetic field, and require only a simple microfluidic chip design and setup. Glass microfluidic devices featuring T-junctions or flow focusing junctions for the generation of oil-based ferrofluid droplets in an aqueous continuous phase were investigated. Droplet size was controlled by the microfluidic channel dimensions as well as the flow rates of the ferrofluid and aqueous phases. The generated droplets were stabilised by a surface active polymer, polyvinylpyrrolidone (PVP), and then guided into a chamber featuring alternating, co-laminar PE solutions and wash streams, and deflected across them by means of an external permanent magnet. The extent of droplet deflection was tailored by the flow rates, the concentration of magnetic nanoparticles in the droplets, and the magnetic field strength. PVP-coated ferrofluid droplets were deflected through solutions of polyelectrolyte and washing streams using several iterations of multilaminar flow designs. This culminated in an innovative “Snakes-and-Ladders” inspired microfluidic chip design that overcame various issues of the previous iterations for the deposition of layers of anionic poly(sodium-4-styrene sulfonate) (PSS) and cationic poly(fluorescein isothiocyanate allylamine hydrochloride) (PAH-FITC) onto the droplets. The presented method demonstrates a simple and rapid process for PE layer deposition in <30 seconds, and opens the way towards rapid layer-by-layer assembly of PE microcapsules for drug delivery applications.
A new approach for high voltage capillary electrophoresis (CE) is proposed, which replaces the st... more A new approach for high voltage capillary electrophoresis (CE) is proposed, which replaces the standard high voltage power supply with a Van de Graaff generator, a low current power source. Because the Van de Graaff generator is a current-limited source (10 μA), potentials exceeding 100 kV can be generated for CE when the electrical resistance of the capillary is maximized. This was achieved by decreasing the capillary diameter and reducing the buffer ionic strength. Using 2 mM borate buffer and a 5 μm i.d. capillary, fluorescently labeled amino acids were separated with efficiencies up to 3.5 million plates; a 5.7 fold improvement in separation efficiency compared to a normal power supply (NPS) typically used in CE. This separation efficiency was realized using a simple set-up without significant Joule heating, making the Van de Graaff generator a promising alternative for applying the high potentials required for enhancing resolution in the separation and analysis of highly complex samples, for example mixtures of glycans.
Despite recent advances in microfluidic-based integrated diagnostic systems, the sample introduct... more Despite recent advances in microfluidic-based integrated diagnostic systems, the sample introduction interface, especially with regards to large volume samples, has often been neglected. We present a sample introduction interface that allows direct on-chip processing of crude stool samples for the detection of Helicobacter pylori (H. pylori). The principle of IFAST (immiscible filtration assisted by surface tension) was adapted to include a large volume sample chamber with a septum-based interface for stool sample introduction. Solid chaotropic salt and dry superparamagnetic particles (PMPs) could be stored on-chip and reconstituted upon sample addition, simplifying the process of release of DNA from H. pylori cells and its binding to the PMPs. Finally, the PMPs were pulled via a magnet through a washing chamber containing an immiscible oil solution and into an elution chamber where the DNA was released into aqueous media for subsequent analysis. The entire process required only 7 min while enabling a 40-fold reduction in working volume from crude biological samples. The combination of a real-world interface and rapid DNA extraction offers the potential for the methodology to be used in point-of-care (POC) devices.
Conventional immunoassays offer selective and quantitative detection of a number of biomarkers, b... more 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.
Amphiphilic microgels of different composition based on the hydrophilic, pH-responsive acrylic ac... more 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.
We present a simple microfluidic system for rapid screening of Escherichia coli (E. coli) O157:H7... more We present a simple microfluidic system for rapid screening of Escherichia coli (E. coli) O157:H7 employing the specificity of immunomagnetic separation (IMS) via immiscible filtration assisted by surface tension (IFAST), and the sensitivity of the subsequent adenosine triphosphate (ATP) assay by the bioluminescence luciferin/ luciferase reaction. The developed device was capable of detecting E. coli O157:H7 from just 6 colony forming units (CFU) in 1 mL spiked buffer within 20 min. When tested with wastewater discharged effluent samples, without pre-concentration, the device demonstrated the ability to detect 10 4 CFU per mL seeded; suggesting great potential for point-of-need microbiological water quality monitoring .
The ability to detect radiation in microfluidic devices is important for the on-chip analysis of ... more The ability to detect radiation in microfluidic devices is important for the on-chip analysis of radiopharmaceuticals, but previously reported systems have largely suffered from various limitations including cost, complexity of fabrication, and insufficient sensitivity and/or speed. Here, we present the use of sensitive, low cost, small-sized, commercially available silicon photomultipliers (SiPMs) for the detection of radioactivity inside microfluidic channels fabricated from a range of conventional microfluidic chip substrates. We demonstrate the effects of chip material and thickness on the detection of the positron-emitting isotope, [(18)F]fluoride, and find that, while the SiPMs are light sensors, they are able to detect radiation even through opaque chip materials via direct positron and gamma (γ) ray interaction. Finally, we employed the SiPM platform for analysis of the PET (positron emission tomography) radiotracers 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [(68)Ga]gallium-citrate, and highlight the ability to detect the γ ray emitting SPECT (single photon emission computed tomography) radiotracer, [99mTc]pertechnetate.
We demonstrate the use of the miniaturised Medipix positron sensor for detection of the clinical ... more We demonstrate the use of the miniaturised Medipix positron sensor for detection of the clinical PET radiotracer, [68Ga]gallium-citrate, on a silica-based monolith, towards microfluidic quality control. The system achieved a far superior signal-to-noise ratio compared to conventional sodium iodide-based radio-HPLC detection and allowed real-time visualisation of positrons in the monolith.
The ability to engage and inspire younger generations in novel areas of science is important for ... more The ability to engage and inspire younger generations in novel areas of science is important for bringing new researchers into a burgeoning field, such as lab-on-a-chip. We recently held a lab-on-a-chip workshop for secondary school students, for which we developed a number of hands-on activities that explained various aspects of microfluidic technology, including fabrication (milling and moulding of microfluidic devices, and wax printing of microfluidic paper-based analytical devices, so-called μPADs), flow regimes (gradient formation via diffusive mixing), and applications (tissue analysis and μPADs). Questionnaires completed by the students indicated that they found the workshop both interesting and informative, with all activities proving successful, while providing feedback that could be incorporated into later iterations of the event.
We demonstrate diamagnetic repulsion forces for performing continuous multilaminar flow assays on... more 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.
Supplementary Information for "On-chip determination of C-reactive protein using magnetic particl... more Supplementary Information for "On-chip determination of C-reactive protein using magnetic particles in continuous flow"
Amphiphilic microgels based on the hydrophilic acrylic acid (AA) and hydrophobic crosslinks of di... more 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.
We demonstrate the application of a multilaminar flow platform, in which functionalized magnetic ... more 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.
Electronic supplementary information for "Radiochemistry on chip: towards dose-on-demand synthesi... more Electronic supplementary information for "Radiochemistry on chip: towards dose-on-demand synthesis of PET radiopharmaceuticals"
We demonstrate the application of magnetic forces for the simultaneous trapping of two types of p... more We demonstrate the application of magnetic forces for the simultaneous trapping of two types of particles, magnetic and diamagnetic, via a single set of magnets. Furthermore, we show how this simple setup can be employed for performing assays with a negative control, or for achieving multiple simultaneous analyses.
Science and Technology of Advanced Materials, 2009
We explore the potential of a microfluidic continuous flow particle separation system based on th... more We explore the potential of a microfluidic continuous flow particle separation system based on the repulsion of diamagnetic materials from a high magnetic field. Diamagnetic polystyrene particles in paramagnetic manganese (II) chloride solution were pumped into a microfluidic chamber and their deflection behaviour in a high magnetic field applied by a superconducting magnet was investigated. Two particle sizes (5 and 10 μm) were examined in two concentrations of MnCl2 (6 and 10%). The larger particles were repelled to a greater extent than the smaller ones, and the effect was greatly enhanced when the particles were suspended in a higher concentration of MnCl2. These findings indicate that the system could be viable for the separation of materials of differing size and/or diamagnetic susceptibility, and as such could be suitable for the separation and sorting of small biological species for subsequent studies.
Superconducting magnets enable the study of high magnetic fields on materials and objects, for ex... more Superconducting magnets enable the study of high magnetic fields on materials and objects, for example in material synthesis, self-assembly or levitation experiments. The setups employed often lack in precise spatial control of the object of interest within the bore of the magnet. Microfluidic technology enables accurate manipulation of fluidic surroundings and we have investigated the integration of microfluidic devices into superconducting magnets to enable controlled studies of objects in high magnetic fields. Polymeric microparticles similar in size to biological cells were manipulated via diamagnetic repulsion. The particles were suspended in an aqueous paramagnetic medium of manganese (II) chloride and pumped into a microfluidic chip, where they were repelled in continuous flow by the high magnetic field. The extent of deflection was studied as a function of increasing (1) particle size, (2) paramagnetic salt concentration, and (3) magnetic field strength. Optimizing these parameters allowed for the spatial separation of two particle populations via on-chip free-flow diamagnetophoresis. Finally, preliminary findings on the repulsion of air bubbles are shown.
We demonstrate a rapid method of coating a layer of polymer onto magnetically modified yeast cell... more We demonstrate a rapid method of coating a layer of polymer onto magnetically modified yeast cells, so-called “cyborg cells”, in continuous flow within a microfluidic chamber. Laminar flow streams of polyelectrolyte and washing buffers were generated across the chamber, and the magnetic cells were deflected sequentially through the co-flowing streams via an external magnet, allowing polyelectrolyte deposition onto the cells immediately followed by the washing step, all in less than 90 s. This simple deposition technique shows promise for the functionalization of such cyborg cells for applications including bioelectronics, bioanalysis, and toxicity screening, while the addition of more reagent streams would enable the fabrication of multilayered capsules.
The continuous flow focussing and manipulation of particles and cells are important factors in mi... more The continuous flow focussing and manipulation of particles and cells are important factors in microfluidic applications for performing accurate and reproducible procedures downstream. Many particle focussing methods require complex setups or channel designs that can limit the process and its applications. Here, we present diamagnetic repulsion as a simple means of focussing objects in continuous flow, based only on their intrinsic properties without the requirement of any label. Diamagnetic polystyrene particles were suspended in a paramagnetic medium and pumped through a capillary between a pair of permanent magnets, whereupon the particles were repelled by each magnet into the central axis of the capillary, thus achieving focussing. By investigating this effect, we found that the focussing was greatly enhanced with (i) increased magnetic susceptibility of the medium, (ii) reduced flow rate of the suspension, (iii) increased particle size, and (iv) increased residence time in the magnetic field. Furthermore, we applied diamagnetic repulsion to the flow focussing of living, label-free HaCaT cells.
The 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2016), Dublin (Republic of Ireland), 9 - 13 October, 2016
We explore the use of the popular videogame, Minecraft, as a tool for educating and inspiring pot... more We explore the use of the popular videogame, Minecraft, as a tool for educating and inspiring potential researchers with regards to the fabrication and operation of microfluidic devices.
European Journal of Nuclear Medicine and Molecular Imaging, 2016
Dose-on-demand production of radiopharmaceuticals has the potential to revolutionise positron emi... more Dose-on-demand production of radiopharmaceuticals has the potential to revolutionise positron emission tomography (PET) medical imaging. Producing a single dose of a desired radiotracer on-site will allow facile adoption of a stratified approach to patient treatment with rapid access to an increased range of radiotracers. We aim to produce modules for lab-on-a-chip device design that can be used for isotope processing, synthesis and quality control tests on a microfluidic scale.
4th Micro and Nano Flows Conference (MNF 14), London (UK), 7 - 10 September, 2014
Microgels are micrometer sized particles consisting of a polymer network that show potential for ... more 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.
4th European Conference on Microfluidics (microFlu’14), Limerick (Republic of Ireland), 10 - 12 December, 2014
We present microfluidic devices for continuous flow generation and deflection of magnetic ferrofl... more We present microfluidic devices for continuous flow generation and deflection of magnetic ferrofluid droplets through laminar reagent streams and demonstrate droplet coating with polyelectrolytes for rapid layer-by-layer (LbL) assembly of drug delivery vesicles. Glass microfluidic devices featuring T-junctions of flow-focusing junctions for the generation of organic droplets in an aqueous continuous phase were investigated. The droplets were then guided into a chamber with parallel reagent and wash streams and deflected across these streams by means of an external magnet. To stabilise the ferrofluid droplets, the surface active polymer poly(vinylpyrrolidone) (PVP) was employed. Droplet size could be controlled by the microfluidic channel dimensions as well as the flow rates of the organic and aqueous phases. In the conditions studied, droplets between 35 and 87 μm diameter could be generated. The deflection of droplets across the microchamber depends on the amount of magnetic material in the droplet, as well as instrumental parameters such as flow rates and magnetic field strength. Ferrofluid droplets were deflected through parallel streams of ink solutions. Furthermore, droplets were deflected through a solution of fluorescently labelled polyelectrolyte, namely, rhodamine123-labelled poly(acrylic acid) (PAA-Rhod123). As the droplets passed the fluorescent reagent stream, a layer of the polyelectrolyte was deposited on the droplet surface. The demonstrated method shows a simple and rapid process for layer deposition (a few seconds) and opens the way towards rapid layer-by-layer assembly of drug delivery capsules.
4th European Conference on Microfluidics (microFlu’14), Limerick (Republic of Ireland), 10 - 12 December, 2014
We report the synthesis of microgels with tailored hydrophilicity/hydrophobicity for drug deliver... more We report the synthesis of microgels with tailored hydrophilicity/hydrophobicity for drug delivery by employing on-chip droplet generation of microgel precursors and downstream photo-polymerization. The microgel size could be controlled precisely from 205 µm to 652 µm diameter (2.0 nL to 4.3 nL) with high monodispersity (coefficient of variation, CV 2-7 %) by adjusting the flow rates of the continuous oil phase and dispersed aqueous phase during droplet formation. Three types of microgel were formed using this setup: hydrophilic poly(ethylene glycol) diacrylate (PEGDA), and hydrophobic poly(propylene glycol) diacrylate (PPGDA), as well as amphiphilic acrylic acid-ethylene glycol dimethacrylate (AA-EGDMA). The amphiphilic AA-EGDMA microgels were obtained by hydrolyzation of hydrophobic droplets containing tetrahydropyran acrylate (THPA) as the protected form of the AA monomer and EGDMA as the crosslinker. The hydrophilicity/hydrophobicity ratio was controlled by varying the molar ratio of THPA and EGDMA between 70:4, 50:4 and 30:4. A higher hydrophilicity/hydrophobicity ratio led to lower crosslinking density and thus a more pronounced swelling of the microgels. The AA-EGDMA microgels were employed for encapsulation and release of a hydrophobic dye (Sudan Red) as well as a hydrophilic dye (Trypan Blue), indicating the potential of these microgels as versatile drug delivery systems.
The 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2015), Gyeongju (Korea), 25 - 29 October, 2015
We present the use of highly sensitive, small footprint, low cost silicon photomultipliers (SiPM)... more We present the use of highly sensitive, small footprint, low cost silicon photomultipliers (SiPM) for radioactivity detection in microfluidic channels, with a view to their integration into miniaturised quality control (QC) platforms for the testing of positron emission tomography (PET) radiopharmaceuticals. While SiPMs are light sensors, it was determined that they are also sensitive to other sources, e.g. direct interaction with positrons and gamma rays, making them suitable for radiation detection with standard chip materials, including those that are opaque, as well as for detection of gamma emitting radiotracers.
The 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2015), Gyeongju (Korea), 25 - 29 October, 2015
We report the on-chip polymerisation of hydrophobic microgels from precursor droplets, and their ... more We report the on-chip polymerisation of hydrophobic microgels from precursor droplets, and their downstream synthesis to pH-responsive amphiphilic microgels for drug delivery. This elegant platform offers superior control over microgel properties, including size, crosslinking density and hydrophobic/hydrophilic properties. The encapsulation and release of hydrophilic (Trypan Blue) and hydrophobic (Sudan Red) dyes based on the microgel shrinking/swelling properties was also studied.
The 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2011), Seattle (USA), 2 - 6 October, 2011
We report on the integration of microfluidic devices and superconducting magnets to enable tempor... more We report on the integration of microfluidic devices and superconducting magnets to enable temporal and spatial control for the application of high magnetic fields in the study of materials and physical phenomena. Here, we perform the continuous flow separation of two particle populations in high magnetic fields based on diamagnetic repulsion, as well as the manipulation of air bubbles.
The 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2014), San Antonio, TX (USA), 26 - 30 October, 2014
We report the synthesis of microgels for drug delivery via on-chip droplet generation and
downst... more We report the synthesis of microgels for drug delivery via on-chip droplet generation and
downstream photo-polymerization which affords control over hydrophobicity/hydrophilicity and enables the synthesis of amphiphilic microgels from hydrophobic droplets. The amphiphilic microgels were found to be effective for encapsulation and release of a hydrophobic dye (Sudan red) as an analog of a drug molecule.
The 13th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2009), Jeju (Korea), 1 - 5 November, 2009
We present temperature control as a simple yet highly efficient means of improving particle separ... more We present temperature control as a simple yet highly efficient means of improving particle separations in on-chip free-flow magnetophoresis. Increased temperatures resulted in a decrease in solution viscosity, which in turn yielded greater particle deflection distances and increased the separation resolution of two particle populations. This inexpensive and effective technique would also be of great benefit to other continuous flow processes involving the deflection of particles.
The 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2013), Freiburg (Germany), 27 - 31 October, Oct 1, 2013
We demonstrate a simple, pump-free platform for performing rapid magnetic bead-based processes vi... more We demonstrate a simple, pump-free platform for performing rapid magnetic bead-based processes via their transfer through sequentially laminated liquid streams, made possible by the use of phaseguide technology. We have applied this strategy to two on-chip assays: (i) a streptavidin-biotin binding assay, and (ii) a sandwich immunoassay for the detection of C-reactive protein (CRP). Here, functionalized magnetic beads were pulled through alternating lanes of reagents and buffer solution, allowing multiple binding and washing processes to be reduced into a single step, significantly shortening procedural times compared to conventional multi-step bead-based assays.
Free-flow magnetophoresis provides a fast and efficient means of continuous flow magnetic separat... more 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.
Journal of Labelled Compounds and Radiopharmaceuticals, 2015
Dose-on-demand radiotracer production, whereby a single dose is generated using a compact synthes... more Dose-on-demand radiotracer production, whereby a single dose is generated using a compact synthesis unit with radioisotope from a minicyclotron or external supply is an interesting prospect for widening the availabilty of radiotracers. Miniaturised synthesis requires miniaturised QC with an platform requiring a small fraction of a dose, rapid operation and no requirement for manual handling.
Dose-on-demand radiotracer production, whereby a single dose is generated using a compact synthes... more Dose-on-demand radiotracer production, whereby a single dose is generated using a compact synthesis unit with radioisotope from a mini-cyclotron or external supply is an interesting prospect for widening the availabilty of radiotracers. We aim to produce modules for lab-on-a-chip device design that can be used for isotope processing, synthesis and some routine quality control tests on a microfluidic scale.
The 13th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2009), Jeju (Korea), 1 - 5 November, 2009
We demonstrate the selective, label-free manipulation of polymer microparticles, including trappi... more We demonstrate the selective, label-free manipulation of polymer microparticles, including trapping, focussing and continuous flow deflection, within microfluidic devices using diamagnetic repulsion forces.
The 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2012), Ginowan (Okinawa, Japan), 28 October - 1 November, 2012
We demonstrate the use of microfluidic modules for purification of the Positron Emission Tomograp... more We demonstrate the use of microfluidic modules for purification of the Positron Emission Tomography (PET) radiotracer, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), as part of an integrated microfluidic Radiochemistry-On-Chip (ROC) platform for complete radiotracer synthesis. Two different modules were applied to the purification of [18F]FDG as synthesized by a commercial system and by initial tests of the ROC platform itself.
The 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2013), Freiburg (Germany), 27 - 31 October, 2013
We present the use of microfluidic devices for copper(II) ion complexation of cyclen and cyclam m... more We present the use of microfluidic devices for copper(II) ion complexation of cyclen and cyclam macrocycles. On-chip monitoring of the complexation reactions was achieved via absorbance detection. This work opens the door for the on-chip synthesis of new 64Cu based radiotracers that are important for positron emission tomography (PET).
The 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2014), San Antonio, TX (USA), 26 - 30 October, 2014
We present on-chip absorbance-based determination of pH and optical clarity for quality control (... more We present on-chip absorbance-based determination of pH and optical clarity for quality control (QC) testing of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), a positron emission tomography (PET) radiotracer. The platform allows fast analysis times, reduces radioactive exposure to personnel, and requires only minimal sample volumes, making it suitable for dose-on-demand radiotracer synthesis.
The 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2014), San Antonio, TX (USA), 26 - 30 October, 2014
We have developed microfluidic devices for the continuous flow coating of magnetic templates (dro... more We have developed microfluidic devices for the continuous flow coating of magnetic templates (droplets/cells) with polyelectrolytes towards rapid layer-by-layer (LbL) assembly of drug delivery capsules. Magnetic ferrofluid droplets and magnetically functionalized yeast cells were deflected across a reaction chamber through reagent and washing streams to achieve fast layer deposition (<10 s).
The 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2014), San Antonio, TX (USA), 26 - 30 October, Oct 1, 2014
Here we report a single point detection method for the characterization of surface properties in ... more Here we report a single point detection method for the characterization of surface properties in microfluidic channels. Our method couples segmented flow (SF) with laser induced fluorescence (LIF) to assess the hydrophobicity of microfluidic channels by analyzing the shape of a fluorescent plug as it moves past a detector. Differences in plug shape are shown to correspond to differences in surface conditions and allow us to distinguish between hydrophobic, partially hydrophobic and hydrophilic surfaces.
Microchip Diagnostics: Methods and Protocols, 2017
Magnetic particles have become popular in recent years for immunoassays due to their high surface... more Magnetic particles have become popular in recent years for immunoassays due to their high surface-to-volume ratio and the ease of their manipulation. However, such assays also require multiple reaction and washing steps that are both time-consuming and manually laborious. Here, we describe a setup and methodology for performing rapid immunoassays on magnetic particles in continuous flow via their deflection through multiple laminar flow streams of reagents and washing solutions. In particular, we focus on the use of the microfluidic platform for a C-reactive protein (CRP) sandwich immunoassay in less than 60 s.
Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, 2013
Microfluidics concerns the manipulation of small volumes of fluids (typically nanoliters or less)... more Microfluidics concerns the manipulation of small volumes of fluids (typically nanoliters or less) within networks of channels that have dimensions of tens to hundreds of micrometers. Such devices benefit from having small footprints, low volume requirements of samples and reagents, short analysis times, and a large degree of control over processes being performed, allowing miniaturization of single or multiple laboratory-based procedures and giving rise to ‘lab-on-a-chip’ technology. Microfluidic platforms have become powerful tools in a broad range of fields, from chemistry and engineering to the life sciences, and are revolutionizing the way research can be performed and the quality of information that can be gained.
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downstream photo-polymerization which affords control over hydrophobicity/hydrophilicity and enables the synthesis of amphiphilic microgels from hydrophobic droplets. The amphiphilic microgels were found to be effective for encapsulation and release of a hydrophobic dye (Sudan red) as an analog of a drug molecule.