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The possibility of using photo-stimulation to perform flow control and sensing in microfluidics is very appealing as light can be applied in a non-invasive and highly precise manner. In the field of stimuli-responsive polymers, hydrogels offer a simple and effective method to fabricate three-dimensional polymeric networks whose water content can be modulated through external stimulation. By incorporating stimuliresponsive units into the gel structure, hydrogels can be actuated by external stimuli such as light, temperature and pH, among others. One of the most popular ways to achieve photo-control is through the use of photo-responsive molecules, such as spiropyrans. This thesis focuses on presenting the synthesis, characterisation and potential applications of stimuli-responsive materials based on spiropyrans, in particular as photo-controlled polymeric actuators, and photo-sensitive coatings. Chapter 1 offers a brief overview of the field of stimuli-responsive materials and photo-responsive materials in particular, and Chapter 2 discusses possible applications of such materials in microfluidic devices. Chapter 3 describes the synthesis and characterisation of photo-responsive hydrogels based on Nisopropylacrylamide- co-acrylated spiropyran-co-acrylic acid (p(NIPAAm-co-SP-co- AA)) copolymer, while in chapter 4 this material is used to produce a millimetresized bipedal hydrogel walker. When subject to light cycles, the bipedal gel produces a walking motion by taking a series of steps in a given direction. Chapter 5 focuses on spiropyran polymeric brushes as coatings in micro-capillaries and confirms their potential for metal ion binding, sensing and release. Chapters 6 focuses on the synthesis and surface functionalisation of other spiropyran derivatives and describes future work in the area of photo-responsive materials and hydrogels.

The continuing interest in stimuli-responsive materials has yielded quite an expansive variety of smart materials that respond to a wide range of stimuli such as electrical current, pH and light, among others [1]. A subclass of this family is comprised of stimuli-responsive hydrogels that are three-dimensional, hydrophilic, polymer networks capable of large water intake. Incorporation of responsive units in such polymeric networks allows for their use as micro-machines capable of doing mechanical work in response to the chosen stimulus. The application of smart materials offers tangible solutions in the field of actuators for microfluidic valves, artificial muscles and biomimetic robots [2-5]. Moreover, new capabilities such as motility, switchable selective uptake and release of molecular agents, sensing, signalling and seeking, will enable microstructures and micro-vehicles to manifest many of the features of biological entities. Herein we explore several bioinspired stimuli-responsive microstructures for actuation and sensing. A particular focus will be the emphasis on the important role of light as a means to enable control and interrogate stimuli-responsive materials, and exploration on how these might provide initial building blocks for creating futuristic microsystems.

Through developments in 3D fabrication technologies in recent years, we can now build and characterize much more sophisticated 3D platforms than was previously possible. We can create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, and regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics, enabling the creation of biomimetic microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and detection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver [1]. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts represents a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realise biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness/self-diagnosis of condition and self-repair capabilities to extend their useful lifetime [2]. In this contribution, I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of futuristic microfluidic systems. Examples will include chemotactic microvehicles that can collaborate to perform sophisticated functions at specific locations [3] and precision control of flow behaviour in channels using light [4]. Strategies for creating high resolution (sub-200 nm) 3D soft-polymer responsive structures will be discussed. References [1] F. Benito-Lopez, R. Byrne, A.M. Răduţă, N.E. Vrana, G. McGuinness, D. Diamond, Ionogel-based light-actuated valves for controlling liquid flow in micro-fluidic manifolds, Lab Chip. 10 (2010) 195–201. doi:10.1039/B914709H. [2] L. Florea, K. Wagner, P. Wagner, G.G. Wallace, F. Benito-Lopez, D.L. Officer, D. Diamond, Photo-Chemopropulsion - Light-Stimulated Movement of Microdroplets, Advanced Materials. 26 (2014) 7339–7345. doi:10.1002/adma.201403007. [3] W. Francis, C. Fay, L. Florea, D. Diamond, Self-propelled chemotactic ionic liquid droplets, Chem. Commun. 51 (2015) 2342–2344. doi:10.1039/C4CC09214G. [4] C. Delaney, P. McCluskey, S. Coleman, J. Whyte, N. Kent, D. Diamond, Precision control of flow rate in microfluidic channels using photoresponsive soft polymer actuators, Lab Chip. 17 (2017) 2013–2021. doi:10.1039/C7LC00368D.

Through developments in 3D fabrication technologies in recent years, it is now possible to build and characterize much more sophisticated 3D platforms than was formerly the case. Regions of differing polarity, binding behaviour, flexibility/rigidity, can be incorporated into these fluidic systems. Furthermore, materials that can switch these characteristics can be incorporated, enabling the creation of microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and selective uptake and release of molecular targets. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required and what science can currently deliver for many challenging applications. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts appears to represent a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realising biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness of condition and self-repair capabilities to extend their useful lifetime. In this contribution I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of these futuristic biomimetic systems.

Through developments in 3D fabrication technologies in recent years, it is now possible to build and characterize much more sophisticated 3D platforms than was formerly the case. Regions of differing polarity, binding behaviour, flexibility/rigidity, can be incorporated into these fluidic systems. Furthermore, materials that can switch these characteristics can be incorporated, enabling the creation of microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and selective uptake and release of molecular targets. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts represents a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realising biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness of condition and self-repair capabilities to extend their useful lifetime. In this contribution I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of these futuristic microfluidic systems. Examples will include chemotactic microvehicles that can collaborate to perform sophisticated functions at specific locations, and precision remote control of flow behaviour in channels using light

Since the initial breakthroughs in the 1960’s and 70’s that led to the development of the glucose biosensor, the oxygen electrode, ion-selective electrodes, and electrochemical/optochemical diagnostic devices, the vision of very reliable, affordable chemical sensors and bio-sensors capable of functioning autonomously for long periods of time (years) remains unrealized. This is despite massive investment in research and the publication of many thousands of papers in the literature. It is over 40 years since the first papers proposing the concept of the artificial pancreas, by combining glucose monitoring with an insulin pump. Yet even now, there is no chemical sensor/biosensor that can function reliably inside the body for more than a few days, and such is the gap in what can be delivered (days), and what is required (years) for implantable devices, it is not surprising that in health diagnostics, the overwhelmingly dominant paradigm for reliable measurements is still single use disposable sensors. Realising disruptive improvements in chem/bio-sensing platforms capable of long-term independent operation requires a step-back and rethinking of strategies, and considering solutions suggested by nature and materials science, rather than incremental improvements in existing approaches. Through developments in 3D fabrication technologies in recent years, we can now build and characterize much more sophisticated 3D platforms than was previously possible. We can create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, and regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics, enabling the creation of biomimetic microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and detection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts represents a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realise biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-diagnosis of condition and self-repair capabilities to extend their useful lifetime.

The continuing interest in stimuli-responsive materials has yielded quite an expansive variety of smart materials that respond to a wide range of stimuli such as electrical current, pH and light, among others [1], and are opening up new concepts in so-called 4D-materials science, in which the 4th dimension is the ability to change materials characteristics over time in a controlled manner using external stimuli. A subclass of this family is comprised of stimuli-responsive hydrogels that are three-dimensional, hydrophilic, polymer networks capable of large water intake. These characteristics make them a potential candidate for the fabrication of biocompatible systems, which can be used for tailored drug delivery and regenerative medicine within the body. Incorporation of responsive units in such polymeric networks allows for their use as micro-machines capable of doing mechanical work in response to the chosen stimulus. The application of smart materials offers tangible solutions in the field of actuators for microfluidic valves, artificial muscles and biomimetic robots [2-5]. Moreover, new capabilities such as motility, switchable selective uptake and release of molecular agents, sensing, signalling and seeking, will enable microstructures and micro-vehicles to manifest many of the features of biological entities. In this talk I will explore several bioinspired microstructures and micro-vehicles including smart droplets and 3D stimuli-responsive microstructures, focusing in particular on the important role of light as a means to enable and control stimuli-responsive materials, and discuss how these might provide initial building blocks for creating futuristic microsystems.

Since the initial breakthroughs in the 1960’s and 70’s that led to the development of the glucose biosensor, the oxygen electrode, ion-selective electrodes, and electrochemical/optochemical diagnostic devices, the vision of very reliable, affordable chemical sensors and bio-sensors capable of functioning autonomously for long periods of time (years) remains unrealized. This is despite massive investment in research and the publication of many thousands of papers in the literature. It is over 40 years since the first papers proposing the concept of the artificial pancreas, by combining glucose monitoring with an insulin pump1. Yet even now, there is no chemical sensor/biosensor that can function reliably inside the body for more than a few days, and such is the gap in what can be delivered (days), and what is required (years) for implantable devices, it is not surprising that in health diagnostics, the overwhelmingly dominant paradigm for reliable measurements is still single use disposable sensors. Realising disruptive improvements in chem/bio-sensing platforms capable of long-term independent operation requires a step-back and rethinking of strategies, and considering solutions suggested by nature and materials science, rather than incremental improvements in existing approaches2. Through recent developments in 3D fabrication technologies in recent years, we can now build and characterize much more sophisticated 3D platforms than was previously possible. We can create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, and regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics, enabling the creation of biomimetic microfluidic building blocks that exhibit photoswitchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable actuation (e.g. valving), and photodetection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver3. The transition from the current paradigm from engineering inspired 2D fluidics to bioinspired 3D fluids is a major milestone in the evolution of microfluidics. Another lesson we can learn from biofluidics is that the entire system is active. Currently, the only role of the substrate in a microfluidic chip is to define the channels. In biology, the channel walls have a very active role, as has the surrounding tissue. Walls can sense, and respond e.g. open pores and release active agents such as functionalised micro/nanoparticles, vesicles, droplets). Implementation of these disruptive concepts may open the way to biochemical sensing systems with performance characteristics far beyond that of current devices. A key development will be the integration of biomimetic functions like self-diagnosis of condition and self-repair capabilities to extend their useful lifetime4.

The integration of stimuli-responsive materials into microfluidic systems can provide a means for external control over fluid flow along with inherent sensing capabilities, which 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 path lengths, 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. 1. Florea, L.; Diamond, D.; Benito-Lopez, F.,. Anal. Chim. Acta 2013, 759, 1-7. 2. Florea, L. et al., Lab Chip 2013, 13, 1079-1085. 3. Florea, L. et al., Sens. Actuators, B 2012, 175, 92-99. 4. Florea, L. et al., Langmuir 2013, 29, 2790-2797.

Photo-responsive hydrogels of varying compositions containing spiropyran photochromic units have been widely studied in recent years due to their many potential applications, including photo-actuated micro-valves for microfluidic devices [1,2]. In this study two hydrogel formulations were employed to produce reversible photo-responsive hydrogel actuators operative in neutral pH. Both compositions contain the photochromic unit spiropyran acrylate (SP) and acrylic acid (AA) copolymerised in the main polymer backbone, together with N-isopropylacrylamide (NIPAAm) or acrylamide (AAm), respectively. At neutral pH, the AA comonomer dissociates to the acrylate anion (A-) and the proton transfers to the SP unit to give the more hydrophilic protonated merocyanine (MC-H+) form, which triggers water uptake and hydrogel expansion. Under white light irradiation, the MC-H+ reverts to the more hydrophobic SP isomer, with simultaneous reformation of acrylic acid, and hydrogel contraction. In the case of p(NIPAAm-co-AA-co-SP) hydrogel, an area contraction of up to 45% of its fully hydrated size was achieved after 4 min of white light exposure followed by reswelling to up to 85% of the initial size after 11 min in the dark. In the case of p(AAm-co-AA-co-SP) hydrogel, the SP unit serves also as a reversible photo-acid generator changing the local pH which in turn determines the ratio of AA/A-, and therefore the hydrophilic character of the polymer backbone. In this case, photo-contraction of ~15% in diameter is achieved within 90 seconds of white light irradiation followed by reswelling to ~95% of its fully hydrated size after further ~30 seconds in the dark. In both cases the photo-induced contraction/reswelling processes were reversible and repeatable over at least 3 cycles with no detectable hysteresis.

Photo-responsive hydrogels of varying compositions containing spiropyran photochromic units have been widely studied in recent years due to their many potential applications, including photo-actuated micro-valves for microfluidic devices [1,2]. In this work two hydrogel formulations were developed producing reversible photo-responsive hydrogel actuators operative in neutral pH. Both compositions contain the photochromic unit spiropyran acrylate (SP) and acrylic acid (AA) copolymerised in the main polymer backbone, together with N-isopropylacrylamide (NIPAAm) or acrylamide (AAm), respectively. At neutral pH, the AA comonomer dissociates to the acrylate anion (A-) transferring the proton to the SP unit to give the more hydrophilic protonated merocyanine (MC-H+) form, which triggers water uptake and hydrogel expansion. Under white light irradiation, the MC-H+ reverts to the more hydrophobic SP isomer with simultaneous reformation of acrylic acid. These simultaneous processes reduce the overall hydrophilicity of the polymeric chain through different mechanisms, triggering hydrogel contraction. In the case of p(NIPAAm-co-AA-co-SP) hydrogel, the optimum composition has resulted in an area contraction of up to 45% of its fully hydrated size after 4 min of white light exposure, followed by reswelling to up to 85% of the initial size after 11 min in the dark. In comparison, optimized p(AAm-co-AA-co-SP) hydrogels have resulted in contraction of ~15% in diameter within 90 seconds of white light irradiation followed by reswelling to ~95% of its fully hydrated size after ~30 seconds in the dark. In both cases the photo-induced contraction/reswelling processes were reversible and repeatable over at least 3 cycles with no detectable hysteresis. These hydrogels were further used for the development of improved photo-responsive valves in microfluidic devices and light guided “walkers” capable of phototactic movement.

Since the initial breakthroughs in the 1960’s and 70’s that led to the development of the glucose biosensor, the oxygen electrode, ion-selective electrodes, and electrochemical/optochemical diagnostic devices, the vision of very reliable, affordable chemical sensors and bio-sensors capable of functioning autonomously for long periods of time (years), and providing access to continuous streams of real-time data remains unrealized. This is despite massive investment in research and the publication of many thousands of papers in the literature. It is over 40 years since the first papers proposing the concept of the artificial pancreas, by combining the glucose electrode with an insulin pump. Yet even now, there is no chemical sensor/biosensor that can function reliably inside the body for more than a few days, and such is the gap in what can be delivered (days), and what is required (minimum 10 years) for implantable devices, it is not surprising that in health diagnostics, the overwhelmingly dominant paradigm for reliable measurements is single use disposable sensors. Realising disruptive improvements in chem/bio-sensing platforms capable of long-term (months, years) independent operation requires a step-back and rethinking of strategies, and considering solutions suggested by nature, rather than incremental improvements in available technologies. Through developments in 3D fabrication technologies in recent years, we can now build and characterize much more sophisticated 3D platforms than was previously possible. Furthermore also we can use hybrid materials – mixtures of organic and inorganic materials, create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics – selecting when and where these behaviours exist. In this talk, I will present a series of examples of biomimetic microfluidic building blocks that exhibit photoswitchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable actuation (e.g. valving), and photodetection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver. These disruptive advances should open the way to long-term implantable devices that can monitor, report and assist the management of an individual’s personal health. A key development will be the integration of self-diagnosis and self-repair capabilities to extend their useful lifetime.

Since the initial breakthroughs in the 1960’s and 70’s that led to the development of the glucose biosensor, the oxygen electrode, ion-selective electrodes, and electrochemical/optochemical diagnostic devices, the vision of very reliable, affordable chemical sensors and bio-sensors capable of functioning autonomously for long periods of time (years), and providing access to continuous streams of real-time data remains unrealized. This is despite massive investment in research and the publication of many thousands of papers in the literature. It is over 40 years since the first papers proposing the concept of the artificial pancreas, by combining the glucose electrode with an insulin pump. Yet even now, there is no chemical sensor/biosensor that can function reliably inside the body for more than a few days, and such is the gap in what can be delivered (days), and what is required (minimum 10 years) for implantable devices, it is not surprising that in health diagnostics, the overwhelmingly dominant paradigm for reliable measurements is single use disposable sensors. Realising disruptive improvements in chem/bio-sensing platforms capable of long-term (months, years) independent operation requires a step-back and rethinking of strategies, and considering solutions suggested by nature, rather than incremental improvements in available technologies.

Hydrogels are three-dimensional polymeric networks that can absorb and retain large quantities of water in relation to their physical size. By incorporating stimuli-responsive units into the gel structure, hydrogel materials can be actuated by external stimuli such as photo[1], thermal, electro and pH, respectively. In this study, pH responsive hydrogels were studied by using copolymers of acrylic acid (AA) and acrylamide (Am) in a 50:50 molar ratio. At pH values above the pKa of AA (pH>4.5) the AA dissociates to the more hydrophilic acrylate anion form (A-) triggering swelling of the hydrogel. In contrast, at pH < 4.5, the hydrogel contracts due to the formation of the less hydrophilic AA form in the polymer backbone, which triggers release of water from the gel. In order to turn this pH response into a photo-response, a reversible photo-acid generator, namely spiropyran acrylate (SP-A), was copolymerised in the polymer backbone using a 10:10:1 molar ratio of AA: Am: SP-A. In acidic environments, the SP-A will spontaneously convert to the protonated hydrophilic merocyanine (MC-H+) form and switch back to the hydrophobic SP-A when exposed to white light, expelling a proton in the process. The switching between these two forms can be used to trigger a localised pH change around the polymer backbone, leading to photo-controlled swelling/contraction due to photo-induced protonation/deprotonation of the AA comonomer. In DI water under dark conditions (A-, MC-H+) the polymer chains are more hydrophilic allowing the hydrogel to expand. However, when exposed to white light, the MC-H+ is converted back to the SP-A form (colourless) expelling a proton, and therefore decreasing the local pH, which in turn causes protonation of the AA making the polymer chains less hydrophilic. The SP-A comonomer acts as a reversible photo-acid generator resulting in a photo-induced change of the local pH, which in turn determines the ratio of AA/A- and therefore the hydrophilic character of the polymer backbone. In this case, photo-contraction of over 15% in diameter is achieved within 90 seconds of white light irradiation followed by reswelling to ~98% of its fully hydrated size after further ~30 seconds in the dark. References [1] ter Schiphorst, J.; Coleman, S., Stumpel, J.E., Ben Azouz, A., Diamond, D. and Schenning, A.P., Chemistry of Materials, 2004, 27(17), 5925-5931.

Imagine a world in which issues related to long-term (months to years) reliability of chem/bio-sensing platforms have been solved, and devices capable of carrying out complex chem/bio-functions in an autonomous manner are ubiquitously available. The potential impact of these technologies socially and economically is enormous, and the demand will be universal, driven by an infinite range of applications. Devices will perform complex analytical measurements while located in remote and environmentally hostile locations, such as the deep oceans, or inside the human body. Their capabilities will go far beyond those of existing devices; chemical sensors, biosensors, lab-on-chip (LOC) systems or autonomous analysers, that cannot deliver the price-performance required for reliable long-term (years) autonomous in-situ operation. Revolutionary device improvements are required to meet this vision, and it is becoming clear that these improvements require a fundamental move towards devices based on bio-inspired approaches. For example, future instrument fluidics will have a much more active role beyond the current tasks of transporting samples, mixing reagents, and cleaning. Much like the circulation systems in living entities, these circulation systems will perform advanced functions, like using mobile micro-scaled biomimetic agents to detect, spontaneously migrate to, and repair damaged channels or fluidic components in order to maintain functional integrity of the device. These strategies, if successful, will be broadly disruptive across many application domains, from chronic disease management to environmental monitoring. In this paper, I will present ideas and strategies through which this exciting vision might be advanced via an exciting combination of stimuli-responsive materials, emerging technologies for precise control of 3D materials morphology (to nanoscale dimensions), and state of the art characterization and visualization techniques.

Hydrogels are three-dimensional polymeric networks that can absorb and retain large quantities of water in relation to their physical size. By incorporating stimuli-responsive units into the gel structure, hydrogels can be actuated by external stimuli such as light[1], temperature[2] and pH[3], among others. In this study pH responsive hydrogels were developed using copolymers of acrylic acid (AA) and acrylamide (Am) in different molar ratios (30:70, 50:50 and 70:30, respectively). In order to turn this pH response into a photo-response, a reversible photo-acid generator, namely spiropyran acrylate (SP-A), was copolymerised in the polymer backbone.

Imagine a world in which issues related to long-term (months to years) reliability of chem/bio-sensing platforms have been solved, and devices capable of carrying out complex chem/bio-functions in an autonomous manner are ubiquitously available. The potential impact of these technologies socially and economically is enormous, and the demand will be universal, driven by an infinite range of applications. Devices will perform complex analytical measurements while located in remote and environmentally hostile locations, such as the deep oceans, or inside the human body. Their capabilities will go far beyond those of existing devices; chemical sensors, biosensors, lab-on-chip (LOC) systems or autonomous analysers, that cannot deliver the price-performance required for reliable long-term (years) autonomous in-situ operation. Revolutionary device improvements are required to meet this vision, and it is becoming clear that these improvements require a fundamental move towards devices based on bio-inspired approaches. For example, future instrument fluidics will have a much more active role beyond the current tasks of transporting samples, mixing reagents, and cleaning. Much like the circulation systems in living entities, these circulation systems will perform advanced functions, like using mobile micro-scaled biomimetic agents to detect, spontaneously migrate to, and repair damaged channels or fluidic components in order to maintain functional integrity of the device. These strategies, if successful, will be broadly disruptive across many application domains, from chronic disease management to environmental monitoring. In this paper, I will present ideas and strategies through which this exciting vision might be advanced via an exciting combination of stimuli-responsive materials, emerging technologies for precise control of 3D materials morphology (to nanoscale dimensions), and state of the art characterization and visualization techniques.

Hydrogels are three-dimensional polymeric networks that can absorb and retain large quantities of water in relation to their physical size. By incorporating stimuli-responsive units into the gel structure, hydrogel materials can be actuated by external stimuli such as photo, thermal, electro and chemical (e.g. pH). In this paper, we demonstrate that the size and volume of a pH sensitive hydrogel based on acrylic acid (AA) and acrylamide (Am) can change when exposed to different pH environments. The pH responsive hydrogels that were developed used copolymers of AA and Am in different molar ratios 30:70, 50:50 and 70:30, respectively. At a pH value above the pKa of AA (pH > 4.5) the AA dissociates to the more hydrophilic acrylate anion (A-) triggering swelling of the hydrogel. In contrast, at pH < 4.5, the hydrogel contracts due to the formation of the less hydrophilic AA form in the polymer backbone, which triggers the release of water from the gel causing it to physically contract. The hydrogel samples were photo-polymerised using a photo-mask with 1mm diameter circles exposed. Each of the hydrogel samples was placed in pH solutions varying from pH 1-14. The hydrogels with 50:50 molar ratio of Am:AA in the polymer backbone produced hydrogels with the highest relative pH response when compared with the other molar ratios, having a large diameter increase from pH 2 (~0.57mm) to pH 10 (~3.27mm). Successive changes of the solution pH showed that the pH-induced actuation is a reversible process with no detectable hysteresis.

Hydrogels constitute a group of hydrophilic polymeric materials, capable of holding large amounts of water in their three-dimensional networks. By incorporating stimuli-responsive units in their structure, hydrogel actuators can be developed, that respond to a variety of stimuli such as light, pH, electric or magnetic fields [1]. In this study, pH responsive hydrogels were developed using copolymers of acrylic acid (AA) and acrylamide (AAm) in different molar ratios (30:70, 50:50 and 70:30, respectively). At pH above the pKa of AA (pH>4.5) the AA dissociates to the more hydrophilic acrylate (A-) form, triggering swelling of the hydrogel (Figure 1). In contrast, at pH < 4.5, the hydrogel contracts due to the formation of the hydrophilic AA form in the polymer backbone, which promotes release of water from the gel (Figure 2). In the case of the 50:50 AAm:AA p(AAm-co-AA), circular hydrogels were polymerised that show an area of 0.72 mm2 at pH 3 compared with 3.56 mm2 for the same hydrogel at pH 11. This dramatic increase of 396.14% is due to the greater amount of the more hydrophilic acrylate ion form being present in basic conditions (Figure 3). In order to turn this pH response into a photo-response, a reversible photo-acid generator, namely spiropyran acrylate (SPA), was copolymerised in the p(AAm-co-AA) polymer backbone. In acidic environments, SPA will spontaneously convert to the protonated hydrophilic merocyanine (MC-H+) form and switch back to the hydrophobic SPA when exposed to white light, expelling a proton in the process (Figure 4). The monomer ratio used for the p(AAm-co-AA-co-SPA) hydrogels was 10:10:1 AAm: AA: SPA. When the hydrogel is immersed in water, in the dark, the AA dissociates and the proton is taken by the SPA to form MC-H+, which gives the hydrogel a yellow colour. Under these conditions (A-, MC-H+) the polymer chains are more hydrophilic causing the hydrogel to expand (Figure 5, initial point t=0s). However, when exposed to white light, the MC-H+ is converted back to the SPA form (colourless) expelling a proton, thus decreasing the local pH, and protonating the AA. This makes the polymer chains less hydrophilic, causing the hydrogel to contract (Figure 5, 0-10 min). Upon removal of the white light source, the reverse process occurs and the initial conditions are restored, resulting in hydrogel expansion (Figure 5, 10-20 min). For the p(AAm-co-AA-co-SPA) hydrogel, the SPA unit serves as a reversible photo-acid generator. This ensures a localised pH change under different illumination conditions, determining the ratio of AA/A- present, and therefore the hydrophilic character of the polymer backbone. In this case, photo-contraction of over 15% in diameter was achieved within 90 seconds of white light irradiation followed by reswelling to ~95% of its fully hydrated size after further ~30 seconds in the dark (Figure 6). In both cases (pH and photo-responsive hydrogels) the stimuli-induced contraction/reswelling processes were reversible and repeatable over at least 3 cycles with no detectable hysteresis [2]. The fast actuation of the p(AAm-co-AA-co-SPA) hydrogels demonstrates great potential for their incorporation in microfluidic systems as reversible photo-controlled micro-valves [3].

Hydrogels are three-dimensional polymeric networks that can absorb and retain large quantities of water in relation to their physical size. By incorporating stimuli-responsive units into the gel structure, hydrogel materials can be actuated by external stimuli such as photo, thermal, electro and pH, respectively. In this study, pH responsive hydrogels were developed by using copolymers of acrylic acid (AA) and acrylamide (Am) in different molar ratios (30:70, 50:50 and 70:30, respectively). At pH above the pKa of AA (pH>4.5) the AA dissociates to the more hydrophilic acrylate (A-) form triggering swelling of the hydrogel. In contrast, at pH < 4.5, the hydrogel contracts due to the formation of the hydrophilic AA form in the polymer backbone, which triggers release of water from the gel. In order to turn this pH response into a photo-response, a reversible photo-acid generator, spiropyran acrylate (SP-A), was copolymerised in the polymer backbone. In acidic environments, the SP-A will spontaneously convert to the protonated hydrophilic merocyanine (MC-H+) form and switch back to the hydrophobic SP-A when exposed to white light, expelling a proton in the process. The switching between these two forms can be used to trigger LCST behaviour in the gel, leading to photo-controlled swelling/contraction due to water uptake and release. The composition used for the photo responsive hydrogel was AA: Am: SP-A in a 10:10:1 molar ratio. When the hydrogel is immersed in water, in the dark, the AA dissociates and the proton is taken by the SP-A to form MC-H+, which gives the hydrogel a yellow colour. Under these conditions (A-, MC-H+) the polymer chains are more hydrophilic causing the hydrogel to expand (Fig. 1, initial point). However, when exposed to white light, the MC-H+ is converted back to the SP-A form (colourless) expelling a proton, decreasing the local pH, and protonating the AA. This makes the polymer chain less hydrophilic and the hydrogel contracts (Fig. 1, 0-10 min). As seen in Fig. 1, this process is reversible and with the initial photo-contraction complete in seconds. After ca. 10 min, the white light is switched off, and the hydrogel reswells to about 95% of its fully hydrated size after ca. 15 min in the dark.

Autonomous chemical sensing platforms capable of operating independently for long periods of time (months, years) at an acceptable cost are not currently available, and it can be argued performance has not advanced significantly despite decades of intensive research. The key issue is how to maintain such devices within calibration, and to validate their calibration status remotely. New approaches to controlling sample and reagent movement in microchannels could play a central role in the realisation of autonomous chemical sensing platforms with capabilities that go well beyond those of existing sensor technologies. Our capacity to create and characterise structures with 3D spatial control ranging from molecular scale through nano, to micro and even macro-dimensions opens exciting new opportunities to understand and mimic the molecular world of biology and chemistry. For example, Figure 1 shows complex 3D structures formed from soft gel-polymers with sub-micron resolution, enabling pores with pre-determined topographies to be created within films and beads. When these polymers incorporate a photo-switchable or chemo-switchable moiety, the pore dimensions can be controlled using light or changes in the local chemical environment. This in turn enables uptake or transfer of material through the pores to be controlled, in a manner similar to many bio-systems. Furthermore, nano-dimensioned features can be created inside microfluidic channels to produce soft polymer actuators for fluid control, or channels with switchable characteristics such as surface roughness [1], or controlled uptake and release of molecular guests. In addition, fluidic coatings can optically report their condition (e.g. whether they are in binding or passive form, or molecular guests are bound) reflecting the chemical status along the entire length of the fluidic system, rather than at a localised detector [2]. The same characteristics can be integrated into micro-vehicles such as droplets, beads and vesicles, or microrobots that can also move spontaneously or be externally directed to specific locations, where they can perform tasks such as autonomous leak detection and repair [3, 4]. Such advanced functions mimic the active behaviour of cells in our own circulation systems, and perhaps provide the pre-cursor to developing analytical devices in which the fluidic system plays a much more active role in condition diagnostics and maintenance in order to extend the functional lifetime of autonomous devices far beyond the current state of the art.

Our capacity to create and characterise structures with 3D spatial control ranging from molecular scale through nano, to micro and even macro dimensions opens exciting new opportunities to understand and mimic the molecular world of biology and chemistry. For example, complex 3D structures can now be formed from soft gel-polymers with sub-micron resolution, enabling pores with pre-determined topographies to be created within films and beads. When these polymers incorporate a photo-switchable or chemo-switchable moiety, the pore dimensions can be controlled using light or changes in the local chemical environment. This in turn enables uptake or transfer of material through the pores to be controlled, in a manner similar to many bio-systems. Furthermore, nano-dimensioned features can be created inside microfluidic channels to produce soft polymer actuators for fluid control, or channels with switchable characteristics such as surface roughness [1], or controlled uptake and release of molecular guests. In addition, fluidic coatings can optically report their condition (e.g. whether they are in binding or passive form, or molecular guests are bound) reflecting the chemical status along the entire length of the fluidic system, rather than at a localised detector [2]. The same characteristics can be integrated into micro-vehicles such as droplets, beads and vesicles, or microrobots that can also move spontaneously or be externally directed to specific locations, where they can perform these and other tasks [3, 4]. In this paper, we will present routes through which these exciting concepts can be practically realized. References 1. J.E. Stumpel, B. Ziolkowski, L. Florea, D. Diamond, D.J. Broer, A. Schenning, Acs Applied Materials & Interfaces, 6 (2014) 7268-7274. 2. L. Florea, C. Fay, E. Lahiff, T. Phelan, N.E. O'Connor, B. Corcoran, D. Diamond, F. Benito-Lopez, Lab on a Chip, 13 (2013) 1079-1085. 3. L. Florea, K. Wagner, P. Wagner, G. G. Wallace, F. Benito‐Lopez, D. L. Officer, D. Diamond, Adv. Mater. 26, 7339 (2014). 4. W. Francis, C. Fay, L. Florea, D. Diamond, Chem. Commun. 51, 2342 (2015).

Our ability to sense chemistry and biology in challenging scenarios, such as implantable devices for monitoring our health, or the quality of water in rivers and lakes has not advanced significantly since the fundamental breakthroughs in chem/bio-sensors of the 1970’s and 1980’s. It is becoming clear that in order to meet challenging performance specifications in terms of price and performance, these devices will have to be much more sophisticated, and in particular, adopt bio-inspired strategies to deliver platforms that can function autonomously for years. For example, many sensing platforms employ fluidic systems, and increasingly microfluidic systems to integrate functions such as sample transport, reagent addition, filtering, and detection. In the future, these fluidic systems will have a more active role in monitoring, reporting and maintaining the overall functionality of the platform. Like our own blood circulation system, fluidics in chem/bio-sensing devices will contain micro/nano-vessels and in-channel active components (e.g. integrated soft-polymer valves) capable of detecting damage, leaks, fouling, channel blockage etc., and furthermore, undertake appropriate remedial action (detect leak location & perform repairs, open blocked channels or provide alternative fluidic pathway) in order to dramatically extend the functional lifetime of the platform. Access to 3D additive technologies, in combination with directed polymer self-assembly, now enables such soft polymer actuators to be created with nano-scale resolution inside microfluidic channels for fluid control, or to provide channels with switchable characteristics such as surface roughness [1], or controlled uptake and release of molecular guests. In addition, fluidic coatings can optically report their condition (e.g. whether they are in binding or passive form, or molecular guests are bound) reflecting the chemical status along the entire length of the fluidic system, rather than at a localised detector [2]. The same characteristics can be integrated into micro-vehicles such as droplets, beads and vesicles, or microrobots that can also move spontaneously or be externally directed to specific locations, where they can perform these and other tasks [3, 4]. In this lecture, I will present practical examples of these exciting concepts and suggest strategies for their further implementation into functional futuristic devices. References 1. J.E. Stumpel, B. Ziolkowski, L. Florea, D. Diamond, D.J. Broer, A. Schenning, Acs Applied Materials & Interfaces, 6 (2014) 7268-7274. 2. L. Florea, C. Fay, E. Lahiff, T. Phelan, N.E. O'Connor, B. Corcoran, D. Diamond, F. Benito-Lopez, Lab on a Chip, 13 (2013) 1079-1085. 3. L. Florea, K. Wagner, P. Wagner, G. G. Wallace, F. Benito‐Lopez, D. L. Officer, D. Diamond, Adv. Mater. 26, 7339 (2014). 4. W. Francis, C. Fay, L. Florea, D. Diamond, Chem. Commun. 51, 2342 (2015).

Since the initial breakthroughs in the 1960’s and 70’s that led to the development of the glucose biosensor, the oxygen electrode, ion-selective electrodes, and electrochemical/optochemical diagnostic devices, the vision of very reliable, affordable chemical sensors and bio-sensors capable of functioning autonomously for long periods of time (years), and providing access to continuous streams of real-time data remains unrealized. This is despite massive investment in research and the publication of many thousands of papers in the literature. It is over 40 years since the first papers proposing the concept of the artificial pancreas, by combining the glucose electrode with an insulin pump. Yet even now, there is no chemical sensor/biosensor that can function reliably inside the body for more than a few days, and such is the gap in what can be delivered (days), and what is required (years) for implantable devices, it is not surprising that in health diagnostics, the overwhelmingly dominant paradigm for reliable measurements is single use disposable sensors. Realising disruptive improvements in chem/bio-sensing platforms capable of long-term (months, years) independent operation requires a step-back and rethinking of strategies, and considering solutions suggested by nature, rather than incremental improvements in available technologies. Through developments in 3D fabrication technologies in recent years, we can build and characterize much more sophisticated 3D platforms than was previously possible. Furthermore also we can use hybrid materials – mixtures of organic and inorganic materials, create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics – selecting when and where these behaviours exist. In this paper we will present a series of examples of biomimetic microfluidic building blocks that exhibit photoswitchable characteristics such as programmed microvehicle movement, switchable binding and release, switchable actuation (e.g. valving), and photodetection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver.

In recent literature, photo-responsive hydrogels have been synthesised by co-polymerisation of N-isopropylacrylamide (NIPAAM) with spiropyran (SP) derivatives. This process demands external protonation of the hydrogels to induce re-swelling, typically by immersing the hydrogel in strong acidic environments. Also the re-swelling times are long, typically up to several hours. These disadvantages have restricted the use of photo-actuated hydrogels to single-use applications. Recently, we reported that the addition of acrylic acid (AA), copolymerised within the hydrogel, provides an internal source of protons that allows photo-actuation in neutral pH environments. [Bartosz, et al. 1] The polymerisation solvent influences the morphology of the hydrogel, by producing porous hydrogels of different pore sizes. This impacts the diffusion path length for water molecules moving in/out of the hydrogel matrix, thus altering the swelling and shrinking kinetics of the hydrogel.[2] In this study photo-actuated hydrogels were generated using p(NIPAAM-co-SP-co-AA) copolymer, in a 100-1-5 mole ratio. Different ratios of water: organic solvent (tetrahydrofran (THF), dioxane and acetone) were used as the polymerisation solvent. This resulted in hydrogels with different pore sizes and different swelling/shrinking and actuation kinetics. By using THF:water (4:1 v:v) as the polymerization solvent, a remarkable contraction in hydrogel size of up to 50% was obtained after four minutes of white light irradiation. Optimising these hydrogels by varying the polymerization solvent has resulted in faster and reproducible shrinking and reswelling cycles. Using the different polymerisation solvents, hydrogel microstructures were photo-polymerised around pillars in-situ inside PDMS/glass microfluidic channels for valve applications. When actuated, the valve contracted thus opening the channel and allowing fluid to flow. The opposite was seen when the valve was kept in the dark. Thus demonstrating successful photo-controlled valves in microfluidic systems.

In recent years, photo-responsive hydrogels reported in the literature have been synthesised by co-polymerisation of N-isopropylacrylamide (NIPAAM) with spiropyran(SP) derivatives. This approach requires external protonation of the hydrogels in order to induce re-swelling, typically by immersing the hydrogel in strongly acidic environments1-3. Moreover, re-swelling times are long, typically up to several hours. These disadvantages have restricted the use of photo-actuated hydrogels to applications that employ single-use methods. Recently, we reported that the addition of acrylic acid copolymerised within the hydrogel provides an internal source of protons that allows photo-actuation in neutral pH environments4. The polymerisation solvent has been shown to directly influence the morphology of the hydrogel, by producing porous hydrogels of different pore sizes5. This has an impact on the diffusion path length for water molecules moving in/out of the hydrogel matrix, thus improving the swelling and shrinking kinetics of the hydrogel6. In this study photo-actuator hydrogels were generated using a N-isopropylacrylamide-co-acrylated spiropyran-co-acrylic acid (p(NIPAAM-co-SP-co-AA) copolymer, in a 100-1-5 mole ratio. Different ratios of organic solvent:water (tetrahydrofran(THF), dioxane and acetone) were used as the polymerisation solvent. Varying the volume ratio of the solvent mixtures, resulted in hydrogels with different pore sizes and therefore different extent of swelling/shrinking and actuation kinetics. For example, when THF:water (4:1 v:v) was used as polymerization solvent, a remarkable contraction in hydrogel size of up to 50% was obtained after four minutes of white light irradiation. Optimising these hydrogels by varying the polymerization solvent has resulted in faster and more reproducible shrinking and reswelling cycles.

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.

Hydrogels are a class of polymeric materials, which swell upon hydration. Hydrogels have been used in many areas such as microfluidic systems where they have the function of pumps or valves [1]. Incorporation of photochromic units in hydrogel materials offers new possibilities for the production of photo-responsive soft actuators[2]. Spiropyrans are one of the most popular classes of photochromic compounds [3]. In acidic environments, the spiropyran gets protonated to form the hydrophilic protonated merocyanine (MCH+) that can be reversed back to the closed hydrophobic spiropyran (SP) by irradiation with white light. Here we demonstrate that the size and volume of a hydrogel comprising a copolymer of acrylated spiropyran can be reduced when exposed to white lig ht irradiation. This causes the gel to shrink and water is expelled. Different ratios of the SP derivative were investigated in order to achieve increased degree of shrinking and improved kinetics. Finally, the newly obtained photo-actuators were polymerized “in situ” in microfluidic channels to obtain photo-actuated microfluidic valves suitable for biomedical applications.

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.

In this paper, I will show how molecular photoswitches can be used to provide key functions for microfluidic systems. In particular, I will focus on the optimisation of effects such as the actuation behaviour of hydrogels incorporating spiropyran derivatives, and the potential impact of these advances on the entire area of microfluidics. In addition, I will also summarise recent developments in photo-chemo-propulsion of micro-droplets in fluidic channels.