This review provides a historical perspective along with a tutorial on the concepts, instrumentation, and progress in the chemical and biological sensing applications of leaky waveguides (LWs) . The ...review compares the sensing performance (i.e. refractive index sensitivity, figure of merit, refractive index resolution, and absorption/scattering/fluorescence sensitivity) of LWs with other label-free optical sensors. As the porosity of the waveguide layer is a primary factor in determining the sensing performance of the LWs, different materials and fabrication methods used to make porous films are also reviewed. Finally, we have discussed the challenges that need to be addressed and the opportunities that can be availed for the development and adoption of LWs for chemical and biological sensing at point-of-need (PoN).
For the first time we have studied an oscillatory chemical reaction (the well-known Belousov-Zhabotinsky (BZ) reaction) in acoustically levitated droplets. Acoustically levitated droplets allow ...wall-less reaction studies, reduce consumption of sample/reagents, offer high throughput measurements, and enable environmentally friendly chemistry by significantly reducing plastic waste. In this work, microdroplets of the BZ reactants were mixed at the central axis of a low-cost acoustic levitator. The chemical reaction observed in acoustically levitated droplets proceeded in the same way as that in both stirred and unstirred vials where the volume of droplets was 750-fold lower than the solutions in vials. The observed oscillation frequency in droplets was lower than that observed in vials, possibly as a result of evaporative cooling of the droplets. This work has shown that oscillatory reactions can be successfully carried out in acoustically levitated droplets, which allows the application of this technique to areas such as analysis, synthesis and actuation of smart materials and studies of the origins of life.
For the first time we have studied an oscillatory chemical reaction (the well-known Belousov-Zhabotinsky (BZ) reaction) in acoustically levitated droplets.
•A novel manifestation has been observed that allows direct observation of the resonance angles of leaky waveguides (LWs).•The phenomenon is only observed for low refractive index mesoporous ...waveguides.•As a result, there is a complete overlap between optical mode and biomolecules, providing high sensitivity.•Qualitative description and mathematical model has been developed to explain the mechanism governing this phenomenon.
We report a very simple biosensor based on the direct observation of leaky waveguide (LW) modes as exponentially decaying interference fringes in the reflectivity curve. This phenomenon was only observed when the refractive index contrast between the waveguide and sample was low (0.002–0.005) and the LW was illuminated with a range of angles of incidence simultaneously. The LW acts as a phase object in angle space, resulting in Fresnel diffraction and formation of interference fringes for each waveguide mode. We present theory, a qualitative explanation and a mathematical model governing the formation of these fringes. The binding of an analyte to recognition elements immobilised in the LW changes its refractive index and thus the angular position of the fringes, which provides the biosensing mechanism. The reported LWs comprised a film of polyacrylamide and copolymers on glass slides, and provided high sensitivity, mass manufacturability and simple instrumentation.
WFH Guidelines for the Management of Hemophilia, 3rd edition Srivastava, Alok; Santagostino, Elena; Dougall, Alison ...
Haemophilia : the official journal of the World Federation of Hemophilia,
August 2020, 2020-08-00, 20200801, 2020-08-01, Letnik:
26, Številka:
S6
Journal Article
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•Leaky waveguide was integrated with electrokinetic preconcentration for rapid and sensitive measurement of proteins.•Enhancement factors between 600 and 930 were obtained, which is ...6–9 times higher than previous reports.•The response time was as low as 60 s, which is up to 16 times faster than previous reports.•Dye was immobilised in the waveguide to visualise the resonance angle and act as a non-specific affinity ligand for proteins.•Label-free sensing combined with electrokinetic preconcentration has a potential way forward to point-of-care diagnostics.
Improving the limit of detection by preconcentration and reducing the response time of optical biosensors are key requirements to enable their use in point of care (PoC) applications. To address these requirements, we have shown that integration of isoelectric focusing (IEF) at a pH step with a leaky waveguide (LW) sensor containing a non-specific affinity ligand (reactive blue 4 dye (RB4)) can reduce the limit of detection of an exemplar protein (bovine serum albumin (BSA)) by a factor of 600–930 and reduce the response time to < 60 s. This is 6–9 times better preconcentration and up to 16 times faster response time than previous reports. IEF was performed with standard ampholytes and with simple acids and bases forming a pH step. Using ampholytes gave good preconcentration, but was much slower than using a pH step. The LW sensor used a thin agarose hydrogel layer into which RB4 was immobilized. The dye acted both as a non-specific affinity ligand and to visualize the waveguide resonances. This allowed the refractive index of the waveguide to be monitored in real time at any point along the 10 mm separation channel length.
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•A Young Interferometer (YI) for real-time imaging of refractive index along the length of microchannels is reported.•The refractive index sensitivity of YI is 2.04 × 10−6 per mm of ...the optical pathlength.•The spatial and temporal resolution is at least 295 μm and 2 s respectively.•Algorithms to obtain phase change and perform phase unwrapping versus channel length and time were developed.•YI was used to monitor electrokinetic transport of protein in agarose filled microchannels in real time.
This report describes a Young interferometer (YI) sensor for real-time imaging of refractive index (RI) along the length of microchannels. The YI comprised a unique combination of Fresnel biprism and cylindrical lens to obtain two wedge shaped light beams, which ultimately overlapped to produce the interference fringes. The measured temporal and spatial resolution of the reported YI is 2 s and 295 μm respectively. The RI resolution per mm of the optical pathlength of the YI sensor is 2.04 × 10−6 while providing information on spatial RI distribution in real-time. The ability of the reported YI to image RI in real-time was used to monitor electrokinetic transport of a model protein, bovine serum albumin (BSA), in agarose filled channels of a microfluidic device. This method is particularly suitable to planar μTAS devices as it is free-space, senses through the entire depth of the channel and requires no coupling devices such as gratings or prisms.
Automation of fluid manipulation is needed to increase throughput and reproducibility of experiments while reducing the time spent by researchers on performing repetitive tasks. Current solutions ...are, however, bulky and expensive, and hence not suited to enable automation in academic laboratories. This work, therefore, reports a low-cost, modular and programmable analytical platform comprising 3-D printed autosampler and peristaltic pump with footprints of 248 mm by 243 mm and 104 mm by 112 mm, respectively. The autosampler consisted of four sample probes/needles that can be driven independently to any of the available solution vials placed along the circumference of a circle. The 3-D printed autosampler developed in this work can access higher number of solution vials independently and is lower cost, but can accommodate fewer solution vials, than commercial devices. The autosampler and peristaltic pump were applied to determine: 1) refractive index sensitivity; 2) porosity; and 3) sensing capability of leaky waveguides (LWs) where the read-out instrument was also 3-D printed. We demonstrated that the automation of fluids enabled by the analytical platform improved the accuracy of results by separating the effect of temperature drifts from analyte solutions from the output of LWs. This work shows that 3-D printed instrumentation can provide results comparable with standard laboratory versions at much lower cost, making it ideal for use in resource-limited settings, and with the possibility of customization as experimental needs change.
•A dye-doped leaky waveguide (DDLW) consisting of a substrate immobilised throughout a hydrogel layer was used to perform enzyme assays by absorption.•The experimental sensitivity of DDLW was 57.5 ...times higher than total internal reflection (TIR) spectroscopy.•The product was unable to diffuse away from the sensing region in the waveguide, avoiding a loss of the absorbance signal.•A high local substrate concentration (1.61mM) was achieved using 7.2pmol of substrate because of the small volume of the waveguide.•Mathematical models governing the operation of DDLW and enzyme diffusion into the waveguide were developed and compared to experimental results.
This work is a proof-of-principle study on the feasibility of performing enzyme bioassays using a dye-doped leaky waveguide (DDLW) where the substrate was immobilised in the entire volume of the waveguide and the fraction of light confined in the waveguide interacted with the absorbing product formed as a result of the enzyme’s action on the substrate. The immobilisation of the substrate in the waveguide offers the following benefits: (1) The coloured product was still immobilised in the waveguide, and thus unable to diffuse away from the sensing region in the waveguide, which would otherwise lead to a rapid loss of the absorbance signal. (2) The interaction between the optical mode and the immobilised product in the waveguide was maximised, resulting in an experimentally determined sensitivity 57.5 times higher than total internal reflection (TIR). (3) Because of the small volume of the waveguide, a high local concentration of ∼1.61mM could be achieved using a small amount of substrate (7.29pmol). This is ∼100 times lower than the case where the same concentration of the substrate solution is present in a microfluidic flow cell of typical dimensions. (4) The high local concentration of the substrate ensured that the rate of product formation was largely dependent on the concentration of the enzyme in the waveguide. This work demonstrated the suitability of DDLW to perform enzyme bioassays using fluorescein diacetate 5(6)-isothiocyanate and esterase, and the formation of fluorescein was monitored by recording changes in the intensity of the reflected light at the resonance angle. The DDLW has potential applications in drug discovery, clinical diagnostics and industrial biotechnology.
Leaky waveguide (LW) biosensors enable accurate measurements using small sample volumes and are cheap to produce, and hence, are advantageous in the area of point-of-use devices. Yet, current ...instrumentation to test LW chips is both bulky and costly because of the use of expensive components, such as glass optics, and manufacturing techniques, such as computer numerical control (CNC) machining. Meanwhile, 3-D printing allows the production of complex shapes that cannot be realized using these techniques, while injection molding allows the low-cost production of optical components. 3-D printed instruments offer huge advantages over traditional laboratory instrumentation, in terms of the cost of the manufacturing equipment required, the cost of the resulting instrumentation, size, and portability. This article describes the design and manufacture of a novel 3-D printed biosensor instrument and demonstrates its use for bioanalysis using LWs with a chitosan waveguide layer. This instrument has a refractive index (RI) resolution comparable to laboratory instrumentation and 3-D printed surface plasmon resonance (SPR) instruments <inline-formula> <tex-math notation="LaTeX">2.37\times 10^{-6} </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">5.90\times 10^{-6} </tex-math></inline-formula>, and <inline-formula> <tex-math notation="LaTeX">1.7\times 10^{-6} </tex-math></inline-formula> RI units (RIUs), respectively and has proven able to detect 133 nM (nmol L −1 ) levels of immunoglobulin G (IgG) via the measurement of the change in resonance angle produced upon the protein binding to the film.
•Dye-doped leaky waveguide (DDLW) consisting of agarose waveguide doped with a dye, reactive blue 4 (RB4), was modelled, fabricated and tested.•Common path simultaneous refractive index and broadband ...absorption measurements were demonstrated using DDLW, which required only a single light source and detector.•DDLW was also used to obtain the absorption spectra of two dyes (RB4 and rhodamine 6G (R6G)) simultaneously to show dye-dye interactions and enhancement of the concentration of R6G.•Anomalous dispersion of R6G was also measured using the DDLW.•The DDLW was shown to be suitable to obtain the absorption spectrum of R6G at concentrations as low as 1μM.
Simultaneous refractive index monitoring and absorption spectroscopy in small volumes common to both measurements using single light source and detector are beneficial, but challenging to perform. This work presents an optical device consisting of a porous waveguide deposited on glass, which is called dye-doped leaky waveguide (DDLW), for this purpose. The waveguide was made of agarose doped with a dye, reactive blue 4. Glycerol and rhodamine 6G were used as an exemplar system to demonstrate the feasibility of DDLW to perform simultaneous refractive index and broadband absorption measurements in a small common volume of 3.5nL. In this case, the immobilised reactive blue 4 permits visualisation of the resonance angle of the waveguide for refractive index monitoring, while the additional absorption caused by the free rhodamine 6G was determined by measuring the wavelength dependent additional losses in the reflectivity profile of the DDLW. The refractive index sensitivity and limit of detection of the DDLW was 106.32±0.97°RIU−1 and 2.82×10−6 respectively. By combining the two measurements, the DDLW was shown to be suitable to monitor the absorption spectrum and anomalous dispersion of rhodamine 6G as well as the nature of its interactions with reactive blue 4. These interactions resulted in enhancing the concentration of the rhodamine 6G in the waveguide by a factor between 119 and 191. The DDLW was shown to be suitable to obtain the absorption spectrum of rhodamine 6G at concentrations as low as 1μM. Future work will focus on the application of the DDLW to characterise analytes/determine parameters of biological significance such as iron loading per molecule of serum ferritin.
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