Reversible photonic hydrogel sensors via holographic interference lithography.

Continuous monitoring of physiological conditions and biomarkers via optical holographic sensors is an area of growing interest to facilitate the expansion of personalised medicine. Here, a facile laser-induced dual polymerization method is developed to fabricate holographic hydrogel sensors for the continuous and reversible colorimetric determination of pH variations over a physiological range in serum (pH 7-9). Readout parameters simulated through a Finite-difference time-domain Yee's algorithm retrieve the spectral response through expansion. Laser lithography of holographic hydrogel sensor fabrication is achieved via a single 355 nm laser pulse to initiate polymerization of ultrafine hydrogel fringes. Eliminating the requirement for complex processing of toxic components and streamlining the synthetic procedure provides a simpler route to mass production. Optimised pH-responsive hydrogels contain amine bearing functional co-monomers demonstrating reversible Bragg wavelength shifts of 172 nm across the entire visible wavelength range with pH variation from 7.0 to 9.0 upon illumination with broadband light. Photolithographic recording of information shows the ability to convey detailed information to users for qualitative identification of pH. Holographic sensor reversibility over 20 cycles showed minimal variation in replay wavelength supporting reliable and consistent readout, with optimised sensors showing rapid response times of <5 min. The developed sensors demonstrate the application to continuous monitoring in biological fluids, withstanding interference from electrolytes, saccharides, and proteins colorimetrically identifying bovine serum pH over a physiological range. The holographic sensors benefit point-of-care pH analysis of biological analytes which could be applied to the identification of blood gas disorders and wound regeneration monitoring through colorimetric readouts.

Doubly Photopolymerized Holographic Sensors.

Holographic sensors are two-dimensional (2D) photonic crystals that diffract narrow-band light in the visible spectrum to quantify analytes in aqueous solutions. Here, a holographic fabrication setup was developed to produce holographic sensors through a doubly polymerization system of a poly-2-hydroxyethyl methacrylate hydrogel film using a pulsed Nd:YAG laser (λ = 355 nm, 5 ns, 100 mJ). Wavelength shifts of holographic Bragg peak in response to alcohol species (0-100 vol %) were characterized. Diffraction spectra showed that the holographic sensors could be used for short-chain alcohols at concentrations up to 60 vol %. The reversibility of the sensor was demonstrated, exhibiting a response time of 7.5 min for signal saturation. After 30 cycles, the Bragg peak and color remained the same in both 20 and 60 vol %. The fabrication parameters were simulated in MATLAB using a 2D finite-difference time-domain algorithm to model the interference pattern and energy flux profile of laser beam recording in the hydrogel medium. This work demonstrates a particle-free holographic sensor that offers continuous, reversible, and rapid colorimetric readouts for the real-time quantification of alcohols.

Towards the real-time monitoring of glucose in tear fluid: holographic glucose sensors with reduced interference from lactate and pH.

Glucose-selective holographic sensors were fabricated from unique tetrahedral 2-acrylamidophenylboronic acid (2-APB) incorporated with co-monomers poly(ethylene glycol) acrylate (PEG), (3-acrylamidopropyl)trimethylammonium chloride (ATMA) and [2-(acryloyloxy)ethyl]-trimethylammonium chloride (AETA) into thin hydrogel films which were transformed into volume holograms using a diffusion method coupled with holographic recording using a frequency-doubled Nd:YAG laser (532 nm). The results showed that the 2-APB-based holographic sensors contracted upon addition of glucose due to the formation of a 2:1 complex between the tetrahedral 2-APB and glucose. More significantly, the 2-APB-based holographic sensors had greatly reduced lactate dependence and a hugely reduced pH effect over the physiological range of pH. These features are vital for development of contact lens-based glucose sensor, where the pH variability is greater (pH 5.8-7.8) and the lactate concentration is substantially higher than in blood. Furthermore, the 2-APB-based holographic sensors also displayed fast response to glucose. The successful union of holograms and the tetrahedral 2-APB receptor for glucose detection in artificial tear fluid is also demonstrated. This new type of holographic sensors responding to glucose with features of minor pH effect and negligible interference from lactate is applicable to the detection of glucose concentrations in tear fluid for the management of diabetes.

Holographic glucose sensors.

A novel holographic sensor system capable of detecting dynamic changes in glucose concentration has been developed. The hologram is recorded within a bio-compatible hydrogel matrix containing phenylboronic acid derivatives. On binding glucose, the colour of the hologram red-shifts to longer wavelengths as the hydrogel expands and this colour change is used to quantify glucose concentration. However, phenylboronic acids are non-selective and bind a wide variety of cis-diols. In blood, glucose is the only sugar found free at high concentration, whilst other sugars are typically found as part of glycoproteins and macromolecular structures. Although glycoproteins have been shown to have no effect on the sensor, phenylboronic acids can bind lactate much more readily than glucose. We have designed two polymer hydrogel systems to increase the selectivity of the sensor for glucose over lactate. The first involved the use of high concentrations of 3-acrylamidophenylboronic acid (3-APB) whilst the second system utilised 2-acrylamido-5-fluorophenylboronic acid (5-F-2-MAPB). Both systems displayed an increased selectivity to glucose over lactate at physiological pH and ionic strength and could be deployed as selective holographic sensors for glucose detection in physiological fluids.

Glucose-sensitive holographic sensors for monitoring bacterial growth.

A glucose sensor comprising a reflection hologram incorporated into a thin, acrylamide hydrogel film bearing the cis-diol binding ligand, 3-acrylamidophenylboronic acid (3-APB), is described. The diffraction wavelength (color) of the hologram changes as the polymer swells upon binding cis-diols. The effect of various concentrations of glucose, a variety of mono- and disaccharides, and the alpha-hydroxy acid, lactate, on the holographic response was investigated. The sensor displayed reversible changes in diffraction wavelength as a function of cis-diol concentration, with the sensitivity of the system being dependent on the cis-diol tested. The effect of varying 3-APB concentration in the hydrogel on the holographic response to glucose was investigated, and maximum sensitivity was observed at a functional monomer concentration of 20 mol %. The potential for using this holographic sensor to detect real-time changes in bacterial cell metabolism was demonstrated by monitoring the germination and subsequent vegetative growth of Bacillus subtilis spores.

Metabolite-sensitive holographic biosensors.

A new type of biosensor that combines the inexpensiveness and mass-produceability of reflection holograms with the selectivity and specificity of enzymes is described. pH-sensitive holographic sensors were fabricated from ionizable monomers incorporated into thin, polymeric, hydrogel films which were transformed into volume holograms using a diffusion method coupled with holographic recording, using a frequency-doubled Nd:YAG laser (532 nm). These holograms were used as transducer systems to monitor the pH changes associated with specific enzymatic reactions to construct prototype urea- and penicillin-sensitive biosensors. The diffraction wavelength (color) of the holographic biosensors was used to characterize their shrinkage and swelling behavior as a function of analyte concentration. The potential of these sensors for the measurement of the clinically and industrially important metabolites urea and penicillin G is demonstrated.

pH-sensitive holographic sensors.

Holographic sensors for monitoring H+ (pH) have been fabricated from ionizable monomers incorporated into thin, polymeric, hydrogel films which were transformed into volume holograms using a diffusion method coupled with holographic recording, using a frequency doubled Nd:YAG laser (532 nm). Unlike other optical pH sensors, it is possible to tailor the operational replay wavelength of the holographic sensor by careful control of the exposure conditions. The holographic diffraction wavelength (color) of the holograms was used to characterize their shrinkage and swelling behavior as a function of pH in various media. The effects of hydrogel composition, ionic strength, temperature, and factors influencing reversibility and response time are evaluated. Optimized holographic pH sensors show milli-pH resolution. The pH-sensing range of the holograms can be controlled through variation of the nature of the ionizable co-monomer used in polymer film construction; a series of holographic sensors displaying visually perceptible, fully reversible color changes over different pH ranges are demonstrated. A poly(hydroxyethyl methacrylate-co-methacrylic acid) holographic sensor was shown to be able to quantify the change in H+ concentrations in real time in a sample of milk undergoing homolactic fermentation in the presence of Lactobacillus casei.

Metal ion-sensitive holographic sensors.

Holographic sensors for Na+ and K+ have been fabricated from crown ethers incorporated into polymeric hydrogels. The methacrylate esters of a homologous series of hydroxyether crown ethers were synthesized and copolymerized with hydroxyethyl methacrylate and the cross-linker ethylene dimethacrylate (3 mol %) to form stable hydrogel films (approximately 10 m thick) containing covalently bound (0-97 mol %) 12-crown-4, 15-crown-5, and 18-crown-6 pendant functionalities. The films were transformed into silver-based volume holograms using a diffusion method coupled with a holographic recording using a frequency-doubled Nd:YAG laser. The resulting holographic reflection spectrum was used to characterize the shrinkage and swelling behavior of the holograms as a function of polymer composition and the nature and concentration of alkali, alkaline earth, and NH4+ ions in the test media. Optimized film compositions containing 50 mol % crown ether showed substantial responses (< or = 200 nm) within 30 s at ion concentrations of < or = 30 mM, which could be rationalized on the basis of the known complexation behavior of the crown ethers. An 18-crown-6 holographic film was shown to be able to quantitate K+ concentrations over the physiologically relevant range. It was virtually unaffected by variations in the Na+ background concentration within the normal physiological variation (approximately 0.13-0.15 M) and shows promise for developing simple, low-cost K+ sensors for medical applications.