Stimuli-responsive materials: developing integrated opto-molecular systems as sensors and actuators in micro-fluidic devices

Micro-fluidic platforms have been conferred with inherent optical sensing capabilities by coating the walls of micro-fluidic channels or micro-capillaries with stimuli-responsive materials. These adaptive materials respond optically to environmental stimuli, such as changes in pH, solvent polarity, the presence of certain metal ions and light. This approach confers sensing capabilities along the entire length of the coated micro-channel or micro-capillary. Adaptive coatings based on two types of materials are presented: 1. Conductive polymer polyaniline - The optical properties of these coatings respond to changes in the pH of the solution that is passing through the micro- channel or micro-capillary, and therefore can be used for dynamic pH monitoring (pH 2-8) or for aqueous ammonia sensing. 2. Photochromic spiropyrans - Photoswitchable coatings based on spiropyran are used to photo-detect solvents of different polarity when passing through the micro-capillary in continuous flow. This sensing behaviour can be switched on/off remotely using light. Finally, it is reported, for the first time, the potential of using spiropyran as a pH pump in fluidic channels for photo-activated chemopropulsion of organic droplets and the solvato-morphological control of self-assembled micro-structures based on spiropyran

Modified polyaniline nanofibres for ascorbic acid detection

Polyaniline nanofibres (PAni) can be surface modified to improve electroactivity over a broader pH range. The technique we describe here can be used to attach carboxylic acid terminated substituents. Modified nanofibres maintain their high surface area, and ability to switch between different redox states. These properties make the material suitable for sensing applications. Unlike unmodified PAni, the functionalised material is self-doping and hence more stable in higher pH solutions. Here we demonstrate how modified PAni fibres can be used for the detection of ascorbic acid

Reversible photo-actuated hydrogels for micro-valve applications

In recent years, a popular way of photo-modulating flow control in microfluidic channels has been through the use of acidified spiropyran (SP) hydrogels that needed to be externally protonated with HCl solutions.1,2 In the swollen protonated merocyanine (MCH+) form, the hydrogel blocks the channels and prevents flow. When exposed to white light, the positively charged MCH+ is converted to the uncharged SP form, triggering shrinking of the hydrogel, and the channel opens. The addition of acrylic acid copolymerised within the hydrogel provides an internal source of protons that allows repeatable photo- actuation in neutral pH environments. Here we report the effect of the polymerization solvent on the shrinking and swelling kinetics of the photo-responsive hydrogel. Using this approach, reversible fast photo-actuated hydrogels have been obtained and have been successfully used for micro-valves applications in micro-fluidic channels

Ocular glucose biosensing using boronic acid fluorophores

Boronic acids (BAs) are well-known for their interactions with diol-containing compounds like glucose. Fluorescent moieties are commonly incorporated into a BA derivative’s framework to monitor the effect of varying glucose concentrations in a given environment. Hence, a novel carboxylic acid fluorescent BA derivative, o-COOHBA, has been investigated for glucose sensing, in solution and when immobilised onto a polydimethylsiloxane (PDMS) “lens”-like surface. This approach aims to develop smart-contact lenses that will allow people suffering from diabetes to track their condition continuously and non-invasively in real-time. 1. Introduction Diabetes is a worldwide incurable disease known to have acute and chronic health effects1-2. This disease affects the cardiovascular and peripheral nervous systems, kidneys, and can also be fatal in some cases1-2. Blindness, heart or kidney failures are among the most common life-threatening effects of diabetes2. Monitoring physiological blood-glucose concentrations is a means of managing the disease, however few non-invasive continuous monitoring methods currently exist1-2. Consequently, there is considerable interested in using aqueous ocular fluid as a sample medium for tracking the disease marker glucose. 2. Sensing Mechanism The Lewis acidic BA moiety of the sensor is known for its strong interaction with electron-rich diols, like sugars1-2. On interaction with sugars, e.g. glucose, the fluorescent BA form is transformed into the anionic boronate form, which is non-fluorescent, leading to a decrease in the fluorescence intensity with increasing sugar concentrations1-2. Scheme 1: Sensing mechanism for BA derivatives. 3. Synthesis of o-COOHBA Sensor A novel BA sensor, o-COOHBA, was synthesized via a one-step nucleophilic substitution reaction that required equimolar quantities of BA and quinoline derivatives, as seen in Scheme 2. The successful formation of o-COOHBA was confirmed by 1H NMR. Scheme 2: Synthesis of o-COOHBA; (i) anhydrous dimethylsulfoxide, N2, 70 0C for 48h. 4. Fluorescence of o-COOHBA Fluorescence measurements were performed on a Jasco FP-8300 Spectrophotometer using a precision cell made from quartz with 10 mm path length. The excitation wavelength required was 380 nm with a corresponding emission wavelength of 485 nm. On increased glucose concentrations, a decrease in fluorescence intensity was observed in the range of 0-10 mM in solution and similarly, in the range of 0-5 mM when anchored to a PDMS surface, corresponding to the ocular-glucose concentrations for diabetics, ~50 μM – 5 mM2. All tests were carried out at an ambient temperature using a pH 7.4 phosphate buffer. 5. Conclusion In both solution studies and when anchored on to the PDMS surface, a decrease in fluorescence intensity was observed on increased glucose concentrations. The excitation wavelength of 380 nm is also advantageous, as it lies close to the visible-region of the electromagnetic spectrum, which allows for the use of cheap, readily available LEDs as excitation sources. The carboxylic acid substituent was desirable for immobilizing the BA sensor onto a wide variety of polymeric substrates

Boronic acid derivatives for sugar sensing

Several boronic acid (BA) derivatives, suitable for sugar sensing (see Figure), have been synthesised via a one-step nucleophilic substitution reaction from the appropriate quinoline starting materials and the benzylboronic acid derivative1. The quinoline moiety confers the fluorescent behaviour of these sensors through its associated conjugated framework. The BA moiety of the sensor is known for its strong interaction with diols and hence, the sugar sensing application1,2. On interacting with sugars (e.g. glucose, fructose and lactose) the fluorescence emission decreases with increasing sugar concentration1. The BA sensors reported previously in the literature (compounds 1, 2, 5 and 6, see Figure), have been found to be suitable for glucose sensing, in the ocular aqueous humour, in which the glucose range for a healthy person is 300-800 μM, increasing to 200-4000 μM for people with diabetes1. As a result, BA sensors have been investigated for glucose sensing when incorporated into platforms, such as smart contact lenses1,2. In this present work, novel BA sensors synthesized for the first time by us (compounds 3, 4, 7 and 8, see Figure), will be compared to BA sensor 1 in terms of their fluorescence, sensitivity to sugars and glucose sensing range

Fabrication of non-enzymatic optical glucose sensors based on boronic acid derivatives

Diabetes is an incurable disease known to have severe acute and chronic side effects, namely blindness, heart disease or kidney failure, among others[1-3]. While monitoring the disease marker glucose in blood prolongs life expectancy, non-invasive continuous monitoring systems currently aren’t available[1-3]. The blood-glucose range for a healthy person is ~3-8mM, increasing to up to 40mM for people with diabetes[3], where the related glucose levels in the ocular fluid are 0.05-0.5mM increasing to up to 5mM for diabetics[3]. Consequently, there is considerable interested in using ocular fluid as a sample medium for tracking the disease marker. In this context, boronic acid (BA) sugar sensors have been investigated for potential use in sensing devices, like smart contact lenses[1-3]. The Lewis acidic BA moiety of the sensor is known for its strong interaction with diols[1-3]. On interaction with diols e.g. sugars, the anionic boronate form is produced leading to a decrease in the fluorescence intensity of the BA sensor with increasing sugar concentrations[1-3]. In this abstract, the synthesis and fluorescence studies of novel BA derivatives for colorimetric sugar sensing are presented. These BA sensors have been synthesised via a one-step nucleophilic substitution reaction[1-2]. The newly synthesised BA sensors were compared in terms of their fluorescence, sensitivity to glucose and their sensing range with the BA sensor - m-[N-[(3-boronobenzyl)-6-methoxyquinolinium bromide]] which has been studied previously for its sugar sensing capabilities at physiological pH[1-2]

Boronic acids for the generation of responsive hydrogels

Several approaches currently exist for continuous monitoring of saccharides, however, to this point most sensors have involved the use of electrochemical approaches based on enzymes, such as glucose oxidase.[1] It is widely accepted that a method of continuous monitoring of glucose would prove highly beneficial for diabetes sufferers. The use of boronic acids to bind saccharides has been investigated for many years as a facile means to monitor the concentration of sacharrides in solution [2]. Successful means of translating such optimised responses to complex polymeric matrices have proved significantly more difficult. Such a feat would prove invaluable for diagnostic and self-regulating systems. Herein we present a family of novel boronic acid derivatives, using an easily-adaptable synthesis. We demonstrate a suite of applications, encompassing self-assembling gels and cross-linked hydrogels, which can bind saccharides and modulate a range of chosen responses. This binding has been probed using a series of different techniques, including optical and impedance spectroscopy. This effect can be exploited within a miniaturised device and monitored using a low-cost photodetector

Stimuli-controlled movement of droplets and polymeric “vehicles”

Stimuli-responsive materials have gained much attention recently as new means for fluid flow control within the field of microfluidics. The ability to control of droplets and polymeric “vehicles” in a contactless manner within microfluidic chips offers new and exciting possibilities such as directed transport of molecular cargo to desired destinations and dynamic sensing of the fluidic environment during movement

Stimuli-responsive materials as sensors and actuators in microfluidic devices

The integration of stimuli-responsive materials into microfluidic systems can provide a means for external control over fluid flow and can reduce the overall complexity of microfluidic devices. Herein we present several approaches for introducing fluid movement and sensing using stimuli-responsive materials. The first approach comprises the use of adaptive nanostructured coatings for direct sensing of flow in continuous flow mode. For this, the inner walls of micro-capillaries and micro-channels were coated with polymeric materials that can be used to detect a variety of target species. Two types of adaptive coatings will be discussed. The first one is based on the conductive polymer polyaniline (PAni) [1,2] while the second consists of polymeric brushes based on spiropyran [3,4]. Using the “grafting” approach homogeneous coatings were obtained on the micro-channel/micro-capillary surface that retained their inherent nano-morphology. The optical proprieties of these coatings change in response to a variety of target analytical species (divalent metal ions, solvents of different polarities, ammonia, H+) passing through the microfluidic device in continuous flow mode. The grafting approach can provide nanostructured to microstructured coatings that combine small diffusion paths with relatively thick optical pathlengths, thereby providing sensitive and fast optical responses to the target analytes. The second approach comprises the use of porous photo-actuated hydrogels as photo-controlled micro-valves in microfluidic systems for repeatable ON/OFF flow modulation in flowing streams over a wide range of pH values (acidic to ca. pH 7.0). Incorporation of such stimuli-controlled structures in microfluidic devices offers unprecedented versatility and external flow control. We envision using these systems to create a new generation of sustainable, low-cost, photonically-controlled and self-reporting fluidic systems