1,721,008 research outputs found
Improved sensitivity and limit-of-detection of lateral flow devices using spatial constrictions of the flow-path
No full textExcel file contains data for the graphs presented in:
Katis, I. et al. (2018). Improved sensitivity and limit-of-detection of lateral flow devices using spatial constrictions of the flow-path. Biosensors & Bioelectronics, 113, 95-100.</span
Laser direct write techniques for the fabrication of paper-based diagnostic devices
No full textWe report on the use of laser direct-write techniques for the fabrication of point-of-care paper-based diagnostic sensors. These include laser-based deposition, laser ablation and laser-induced photo-polymerisation.Firstly, Laser Induced Forward Transfer (LIFT) was employed to deposit biomolecules from a donor film onto paper receivers. Paper was chosen as the ideal receiver because of its inherent properties which make it an efficient and suitable platform for point-of-care diagnostic sensors. Both enzyme-tagged and untagged antibodies were LIFT-printed and their viability was confirmed via a colorimetric enzyme-linked immunosorbent assay (ELISA).Secondly, we report on the laser-based structuring of paper-based fluidic devices. Laser-scanning the paper defines the areas that will be polymerised, thus creating barriers that keep the liquid solutions contained. Complicated devices are easy to fabricate and the flexibility of this technique allows for unique patterns, making it appropriate for rapid prototyping but also for large-scale production. Furthermore, the laser patterning technique allows control of the depth or degree of polymerisation, thereby allowing the liquid to wick through but also imposition of flow delays.Finally, the use of lasers for the fabrication of a 'master' which can be used for casting a PDMS mould for applications in micro-contact printing. The combination of the above mentioned techniques represent the platform technology for the rapid, precise and versatile laser-based fabrication of diagnostic point-of-care sensors
Laser-direct-write (LDW) methods for fabrication of paper-based medical diagnostic sensors
No full textLocal deposition assisted laser-based direct-write method for fabrication of paper-based microfluidic devices
No full textDemand for low-cost alternatives to conventional medical diagnostic tools has been the driving force that has spurred significant developments in the diagnostics field. Paper-based fluidic devices, proposed by the Whitesides’ group in 2007 have been regarded as one such alternative, and consequently, this field has been progressing rapidly.In our previous works, we have demonstrated the usefulness and versatility of a laser direct-write (LDW) approach in the patterning of fluidic devices in porous materials such as cellulose for the fabrication of diagnostic devices. This lab-based non-lithographic approach with high flexibility has the potential to be up-scaled for mass-production of paper-based devices at affordable costs. A decrease in the total number of fabrication-steps would however not only make this LDW process more efficient as a consequence of reduced fabrication times, but would also make it more cost-effective because of the reduced usage of expensive reagent – translating it into a truly mature technique adoptable for commercial manufacture. To optimise our original technique, we propose the inclusion of a deposition tool that allows localised deposition of the photopolymer at only specific locations on the paper where the fluid containing wall/structures need to be formed within the substrates to create the microfluidic device. This selective photopolymer deposition eliminates the (global) soaking step required to impregnate the photopolymer within the paper, prior to the laser illumination step, and furthermore also makes redundant the subsequent solvent developing step inherent in our original technique.Overall, we believe this optimised LDW technique is suitable for roll-to-roll manufacture of paper-based microfluidic devices that can be used for a variety of applications
Flow control in laser-patterned paper-based point-of-care (POC) diagnostic devices
No full textIn recent years, the requirements for easy-to-use, low-cost and accurate diagnostic solutions have led to a rapid progress in the research of POC diagnostic devices, especially lab-on-chip (LOC) type POC devices with origins in the 1990s [1]. Paper-based microfluidic devices, which are regarded as a low-cost alternative to conventional POC diagnostics tools, have also been popularly studied in the last decade because of the advantages they present - affordable, mass producible, disposable via incineration etc. [2] A numbers of research groups have focused onto developing fabrication methodologies, and during the past five years, several methods such as photolithography, inkjet printing, printing of wax, laser cutting etc. have already been reported [3].Although, paper is an excellent substrate wherein fluids naturally wick via capillary forces, and hence there are no requirements for external pumps to transport liquids within a paper-based device, unfortunately, the physical properties inherent with porous substrates offer limited control over fluid transport, especially with regards the flow-rate and direction of flow. This presents a critical drawback which restricts the creation of paper-based devices with complex functionalities, limiting their impact in the analytical community [3]. Therefore, research into the development of methodologies that control the flow of fluids in paper-based devices is urgently needed, and this will lead to better liquid handling and autonomous operation within the paper-based device for integrating of additional functionalities. In this report, we present our two new methodologies that allow for the control of the fluid flow in paper-based microfluidic devices: programmable flow-delay and 3 dimensional (3D) flows. Both controls are achieved using the same simple laser-based direct-write (LDW) procedure, which we have previously reported for fabrication of paper-based devices based via light-induced photo-polymerisation route [4]. Firstly, programmable flow-delay was enabled via two different fluid delay mechanisms, namely, by the formation of delay-barriers within flow paths and which are either permeable ‘delay-barriers’ with variable porosity or impermeable barriers with variable depth. Both mechanisms allow the introduction of pre-programmed or timed fluid delivery in paper-based fluidic devices. The depth or the porosity of these delay-barriers can be easily adjusted via changing the laser patterning parameters, such as the incident laser power and the writing speed. Both types of barriers yield similar results for control over the fluid flow. The resulting flow-delay was observed to depend not only on the characteristics (porosity or depth) of the delay-barriers but also on the number of barriers and the position of the barriers within the flow path. Using these delay patterning protocols we have generated flow delays which span from a few minutes to over half an hour. Secondly, the same LDW method was also extended for fabrication of 3D flow path in paper-based devices, which again allows controllable distribution of fluids, however, in both the lateral (in the paper plane) and vertical directions. In brief, by controlling the laser patterning conditions, we could produce solid hydrophobic structures either partially inside a single layer of paper or all the way through a few layers of paper. Thus by selectively patterning from both sides of the paper we could fabricate 3D flow paths within both a single layer of paper and a stack containing multiple layers of paper. In conclusion, a number of advantages can be enabled through the implementation of these flow control methodologies, however, it further also provides an important advantage over other routes because it the same laser-patterning procedure that allows the fabrication of both the device and the flow control pathways. Additionally, in contrast to other methods reported for producing flow control in paper-based devices, our approach eliminates the requirements for cleanroom-based infrastructure, or custom-designed equipment, or even the need for proprietary materials. Above all, we believe that this integrated laser-based patterning process presents a simple route for commercial-scale manufacturing and hence could be an ideal choice for rapid fabrication of affordable, custom-designed paper-based microfluidic devices for realisation of both single-step or multi-step analytical tests
Laser direct-write for fabrication of three-dimensional paper-based devices
No full textWe report the use of a laser-based direct-write (LDW) technique that allows the design and fabrication of three-dimensional (3D) structures within a paper substrate that enables implementation of multi-step analytical assays via a 3D protocol. The technique is based on laser-induced photo-polymerisation, and through adjustment of the laser writing parameters such as the laser power and scan speed we can control the depths of hydrophobic barriers that are formed within a substrate which, when carefully designed and integrated, produce 3D flow paths. So far, we have successfully used this depth-variable patterning protocol for stacking and sealing of multi-layer substrates, for assembly of backing layers for two-dimensional (2D) lateral flow devices and finally for fabrication of 3D devices. Since the 3D flow paths can also be formed via a single laser-writing process by controlling the patterning parameters, this is a distinct improvement over other methods that require multiple complicated and repetitive assembly procedures. This technique is therefore suitable for cheap, rapid and large-scale fabrication of 3D paper-based microfluidic devices
Programmable delay in paper-based devices using laser direct writing
No full textDemand for low-cost alternatives to conventional medical diagnostic tools has been the driving force that has spurred significant developments in the diagnostics field. Paper-based fluidics, proposed by the Whitesides’ group in 2007 has been regarded as one such alternative, and consequently, this field has been progressing rapidly and a range of paper-based fluidic devices that implement different assays have since been demonstrated. Research into the development of methodologies that control, and in particular delay the flow of fluids in these devices is an urgently needed requirement that would enable greater functionalities in such paper-based devices.In this work, to control fluid-flow, we report the use of a new approach that is based on the laser-based photo-polymerisation technique that we have reported earlier for the creation of fluidic patterns (channels/wells) in paper. The delay or slowing down, of the fluid-flow in a fluidic channel is achieved via the introduction of barriers aligned across the direction of the fluid-flow – in a fashion similar to how speed-bumps enable traffic-calming control on a road. The schematic in Figure 1a shows how the delay can be introduced via the creation/insertion of barriers which are solid and impermeable and by controlling the ‘depth’ of the solid/impregnable barriers (Figure 1) to allow for controlled leakage of the fluids under the barriers. The control over the depth of the barriers is obtained by simply adjusting the laser-writing parameters such as the output power and writing/scanning speed. We observe that solid/impregnable barriers of various depths decrease the fluid flow by a rate that is proportional to their depth. Having patterned these barriers at pre-defined locations in the fluidic channel, using a pulsed laser operating at 266nm (20Hz, 10ns) we have achieved flow-delays with a time span ranging from few minutes to over an hour. We have also performed a study to understand the influence of the number of barriers and their position on the flow-delay, and this is shown in Figure 2.Since the channels and flow-delay barriers can be written via a common laser-writing procedure, this technique has a distinct advantage over certain other methods that require specialist operating environments, or custom-designed equipment to enable both these aspects. We believe this rapid and versatile technique is therefore suited for fabrication of ‘sample-in-read-out’ type automated paper-based microfluidic devices that can implement single/multistep analytical assays
Bacterial pathogen detection using laser-structured paper-based diagnostic sensors
No full textAntimicrobial resistance has been recently identified by the World Health Organisation as a global threat and the need for novel diagnostic tools has been stressed. Current routine empirical antibiotic therapy protocol involves laboratory-based bacterial culture testing which can take up to 2-3 days. However, if the specific microbe species causing an infection can be quickly identified earlier on, it will allow doctors to prescribe a specific targeted antimicrobial instead of using a broad spectrum antimicrobial. In this work, we will present our preliminary results on the use of a laser-based fabrication technique of paper-based diagnostic tests via photo-polymerisation. The technique allows the creation of hydrophobic barriers through the whole thickness of the paper, and therefore the creation of fluidic channels and test zones in many different shapes, sizes and patterns. The laser-based direct-write procedure is non-contact, non-lithographic and mask-less and uses a low-power 405nm diode laser. The laser-structured paper can then be infused with chromogenic agars that allow the growth and detection of different bacteria. These devices are analogues of the commonly available agar plates and will allow the timely detection of multiple pathogens at the point-of-care. These paper-based diagnostic sensors fabricated via our laser-based technology are cheap, easy-to-use and allow rapid testing of either pathogens or their antimicrobial resistance to antibiotics
Local deposition assisted laser direct-write technique for fabrication of paper-based microfluidic devices
No full textIn recent years, the requirements for easy-to-use, low-cost and accurate diagnostic solutions have led to rapid progress in the development of in-vitro point-of-care (POC) diagnostic devices, especially lab-on-chip type POC devices. Paper-based micro-analytical devices, proposed by the Whitesides’ group have gained widespread popularity as alternatives to traditional diagnostics. Several methods such as wax printing, UV lithography etc. have already been reported for creating such fluidic devices in paper. In our previous works, we have demonstrated the usefulness and versatility of a laser direct-write (LDW) technique in the patterning of fluidic devices in porous materials for creation of diagnostic devices and have proved its potential as a technique that can be up-scaled for mass-production of paper-based devices at affordable cost. To further improve, optimise and simplify this approach, we propose the inclusion of a local-deposition procedure that involves the deposition of the photopolymer only at desired locations on the paper platform. As in the schematic (Fig.1) describing the local-deposition assisted LDW setup, the photopolymer is first locally deposited onto the paper substrate via a deposition nozzle at designated locations, and a laser beam subsequently illuminates the deposited patterns to induce curing of the photopolymer. The solidified patterns produced through the curing define the fluidic walls that confine and transport the liquids within the porous substrate. In addition, the non-contact nature of the fabrication process renders the platform substrate unaltered and the device free of contaminants. Furthermore, we show the possibility of creating devices with unique advantages such as the creation of surface-relief structures (Fig.2) that help avoid overflow and hence devices that can handle large volumes.We have demonstrated fabrication speeds of >1m/s making the local-deposition assisted LDW process well-suited for rapid and cost-effective roll-to-roll manufacture of paper-based microfluidic devices for a varied set of applications
Laser direct-write technique for rapid multiplexed detection on lateral-flow devices
No full textPaper-based lateral flow devices (LFD) that allow rapid non-quantitative detection of a single analyte in a fluidic sample, within a time-span of 5-30 minutes are regarded as ideal diagnostic solutions for point-of-care (POC) scenarios, especially for the under-resourced settings of developing countries with remote poorly accessible regions. In recent years, there has been an increasing need for performing multiplexed diagnostics at the POC for rapid and simultaneous detection of multiple analytes within a single sample. Currently, only a few commercial LFDs provide such multiplexing either by laminating together different individual LFDs or alternatively, by multiplexing within a single flow-path. Such devices have critically- inherent drawbacks such as, for the former, increased device dimensions and therefore need for larger sample volumes, and for the latter, an undesired interference between different detection sites, i.e. the influence of each of the previous test-lines on subsequent lines positioned further along the flow-path.Herein, to overcome both these limitations, we propose a novel solution – a multi-path LFD (Fig.1) created via the precise partition of the flow-path of a single LFD using our previously reported, proprietary laser direct-write (LDW) technique. The multiple flow-paths allow individual detection of the different analytes in each of the separated channels. Fig.1a shows the schematic of an example three-channel LFD that can be used for simultaneous detection of three different analytes within the same sample. The appearance of coloured test lines in individual channels indicates the presence of the different analytes. Fig.1b shows the use of this three-channel LFD for multiplexed detection of a biomarker panel comprising C-reactive protein, Serum amyloid A-1 and Procalcitonin, used for the diagnosis of bacterial infections.In conclusion, we demonstrate the use of our LDW technique for the creation of multiple flow-paths within a ‘single’ LFD, which allows multiplexed detection, and thereby a hugely improved detection-efficiency
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