Responsive polymer materials can adapt to surrounding environments, regulate transport of ions and molecules, change wettability and adhesion of different species on external stimuli, or convert chemical and biochemical signals into optical, electrical, thermal and mechanical signals, and vice versa. These materials are playing an increasingly important part in a diverse range of applications, such as drug delivery, diagnostics, tissue engineering and 'smart' optical systems, as well as biosensors, microelectromechanical systems, coatings and textiles. We review recent advances and challenges in the developments towards applications of stimuli-responsive polymeric materials that are self-assembled from nanostructured building blocks. We also provide a critical outline of emerging developments.

Emerging applications of stimuli-responsive polymer materials

Dipstick and lateral-flow formats have dominated rapid diagnostics over the last three decades. These formats gained popularity in the consumer markets due to their compactness, portability and facile interpretation without external instrumentation. However, lack of quantitation in measurements has challenged the demand of existing assay formats in consumer markets. Recently, paper-based microfluidics has emerged as a multiplexable point-of-care platform which might transcend the capabilities of existing assays in resource-limited settings. However, paper-based microfluidics can enable fluid handling and quantitative analysis for potential applications in healthcare, veterinary medicine, environmental monitoring and food safety. Currently, in its early development stages, paper-based microfluidics is considered a low-cost, lightweight, and disposable technology. The aim of this review is to discuss: (1) fabrication of paper-based microfluidic devices, (2) functionalisation of microfluidic components to increase the capabilities and the performance, (3) introduction of existing detection techniques to the paper platform and (4) exploration of extracting quantitative readouts via handheld devices and camera phones. Additionally, this review includes challenges to scaling up, commercialisation and regulatory issues. The factors which limit paper-based microfluidic devices to become real world products and future directions are also identified.

Paper-based microfluidic point-of-care diagnostic devices

Recent developments in paper-based microfluidic devices.

Lanthanide Nanoparticles: From Design toward Bioimaging and Therapy

Cerium oxide nanoparticles have the unique power to act as both oxidation and reduction catalysts, thanks to the ability of cerium to rapidly switch between two oxidation states. Can Xu and Xiaogang Qu from the Chinese Academy of Sciences review how this dual catalytic activity yields enzyme-like behavior that can be harnessed for cancer-detecting assays and new biomedical applications. The nanoparticles mimic enzyme species, such as superoxide dismutases and catalases, that repair the damage caused by free radicals and reduce harmful reactive oxygen levels in the body. With tiny dimensions that allow them to enter cellular spaces inaccessible to traditional medicines - including crossing the blood-brain barrier for Alzheimer's disease treatments - these nanomaterials may offer potent remedies against degenerative diseases. Xu and Qu stress the need for systematic biological testing, however, to resolve possible toxicity concerns.

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Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications

We report the first use of redox nanoparticles of cerium oxide as colorimetric probes in bioanalysis. The method is based on changes in the physicochemical properties of ceria nanoparticles, used here as chromogenic indicators, in response to the analyte. We show that these particles can be fully integrated in a paper-based bioassay. To construct the sensor, ceria nanoparticles and glucose oxidase were coimmobilized onto filter paper using a silanization procedure. In the presence of glucose, the enzymatically generated hydrogen peroxide induces a visual color change of the ceria nanoparticles immobilized onto the bioactive sensing paper, from white-yellowish to dark orange, in a concentration-dependent manner. A detection limit of 0.5 mM glucose with a linear range up to 100 mM and a reproducibility of 4.3% for n = 11 ceria paper strips were obtained. The assay is fully reversible and can be reused for at least 10 consecutive measurement cycles, without significant loss of activity. Another unique featur...

Paper Bioassay Based on Ceria Nanoparticles as Colorimetric Probes

A biomolecular security system mimicking a keypad lock device was developed using enzyme-based concatenated AND logic gates resulting in the implication logic network.

Biocomputing Security System: Concatenated Enzyme-Based Logic Gates Operating as a Biomolecular Keypad Lock

A new signal-responsive interface with switchable/tunable redox properties based on a pH-responding polymer brush was studied. Poly(4-vinyl pyridine), P4VP, functionalized with Os-complex redox units was grafted to an indium tin oxide (ITO) conductive support in the form of a polymer brush. The modified electrode surface was responsive to the changes of the pH value of the electrolyte solution: at acidic pH = 4.0 the redox-polymer film demonstrated the reversible electrochemical process, E° = 0.29 V (vs Ag/AgCl), while at neutral pH > 6, the polymer was not electrochemically active. The reversible transformation between the active and the inactive state originated from the structural changes of the polymer support. The protonation of the pyridine units of the polymer backbone at the acidic pH resulted in the swelling of the polymer brush allowing quasi-diffusional translocation of the flexible polymer chains, thus providing direct contact of the polymer-bound redox units and the conducting electrode suppo...

Polymer Brush-Modified Electrode with Switchable and Tunable Redox Activity for Bioelectronic Applications

A new type of paper based bioassay for the colorimetric detection of phenolic compounds including phenol, bisphenol A, catechol and cresols is reported. The sensor is based on a layer-by-layer (LbL) assembly approach formed by alternatively depositing layers of chitosan and alginate polyelectrolytes onto filter paper and physically entrapping the tyrosinase enzyme in between these layers. The sensor response is quantified as a color change resulting from the specific binding of the enzymatically generated quinone to the multilayers of immobilized chitosan on the paper. The color change can be quantified with the naked eye but a digitalized picture can also be used to provide more sensitive comparison to a calibrated color scheme. The sensor was optimized with respect to the number of layers, pH, enzyme, chitosan and alginate amounts. The colorimetric response was concentration dependent, with a detection limit of 0.86 (±0.1) μg/L for each of the phenolic compounds tested. The response time required for th...

Colorimetric Paper Bioassay for the Detection of Phenolic Compounds

Biochemical systems that demonstrate the Boolean logic operations AND, OR, XOR, and InhibA were developed by using soluble compounds, which represent the chemical "devices", and the enzymes glucose oxidase (GOx), glucose dehydrogenase (GDH), alcohol dehydrogenase (AlcDH), and microperoxidase-11 (MP-11), which operated as the input signals that activated the logic gates. The enzymes were used as soluble materials and as immobilized biocatalysts. The studied systems are proposed to be a step towards the construction of "smart" signal-responsive materials with built-in Boolean logic.

Maryna Ornatska

Papers

Paper Bioassay Based on Ceria Nanoparticles as Colorimetric Probes

Biocomputing Security System: Concatenated Enzyme-Based Logic Gates Operating as a Biomolecular Keypad Lock

Polymer Brush-Modified Electrode with Switchable and Tunable Redox Activity for Bioelectronic Applications

Colorimetric Paper Bioassay for the Detection of Phenolic Compounds

Boolean Logic Gates that Use Enzymes as Input Signals