Closed-loop recyclable plastics from poly(ethyl cyanoacrylate).

Ethyl cyanoacrylate is a highly reactive monomer that has been used nearly exclusively to make Super Glue and related fast-setting adhesives. Here, we describe transformation of this highly abundant, readily available monomer into a closed-loop recyclable plastic that could supplant currently used (and often unrecycled/unrecyclable) plastics, such as poly(styrene). We report polymerization conditions, plastic-processing methods, and plastic-recycling protocols for poly(ethyl cyanoacrylate) plastics that make the Super Glue monomer a viable starting material for a next generation of closed-loop recyclable plastics. The processes described are scalable, and the plastics can be recycled in a closed-loop process with >90% yields, even when combined with a heterogeneous mixture of other types of plastic.

Poly(carboxypyrrole)s That Depolymerize from Head to Tail in the Solid State in Response to Specific Applied Signals.

This Article describes the design, synthesis, and analysis of a new class of polymer that is capable of depolymerizing continuously, completely, and cleanly from head to tail when a detection unit on the head of the polymer is exposed to a specific applied signal. The backbone of this polymer consists of 1,3-disubstituted pyrroles and carboxy linkages similar to polyurethanes. Diverse side chains or reactive end-groups can be introduced readily, which provides modular design of polymer structure. The designed depolymerization mechanism proceeds through spontaneous release of carbon dioxide and azafulvene in response to a single triggering reaction with the detection unit. These poly(carboxypyrrole)s depolymerize readily in nonpolar environments, and even in the bulk as solid-state plastics.

Self-Propagating Amplification Reactions for Molecular Detection and Signal Amplification: Advantages, Pitfalls, and Challenges.

Self-propagating cascade reactions are a recent development for chemo-sensing protocols. These cascade reactions, in principle, offer low limits of detection by virtue of exponential signal amplification, and are initiated by a specific, pre-planned molecular detection event. This combination of selectivity for a detection event followed by in situ signal amplification is achieved by exploitation of mechanistic organic chemistry, and thus has resulted in various chemo-sensing protocols that employ one or more reagents to achieve the desired selectivity and sensitivity for an assay. Species such as hydrogen peroxide, thiols, and fluoride, have been used as active reagents to initiate the first examples of self-propagating signal amplification reactions, although many other active reagents should be compatible with the approaches. A common feature of the reagents that support the self-propagating signal amplification reactions is the involvement of quinonemethide intermediates resulting from elimination of optical reporters and/or active reagents, where the latter propagates the signal amplification reaction. The early examples of these amplification sequences, however, are slow to reach full signal, thus leaving time for background reactions to generate non-specific signals. This issue of background has limited practical applications of these self-propagating signal amplification reactions, as has challenging synthetic routes to the reagents, as well as the potential for other chemical species to interfere with the detection and signal amplification processes. Thus, the goal of this review is to summarize the progress of self-propagating signal amplification technology, identify the pitfalls of current designs, and by doing so, to stimulate future studies in this growing and promising research area.

Coupling Activity-Based Detection, Target Amplification, Colorimetric and Fluorometric Signal Amplification, for Quantitative Chemosensing of Fluoride Generated from Nerve Agents.

The G-class nerve agents, which include sarin, soman, and cyclosarin, react readily with nucleophilic reagents to produce fluoride. Thus, a chemosensing protocol has been designed for these agents that pairs the nucleophilic reactivity of oximates for generating fluoride with an autoinductive target amplification reaction to amplify the quantity of fluoride for facile colorimetric and fluorescent optical quantification. The chemosensing protocol was demonstrated by using the nerve agent surrogate diisopropyl fluorophosphate (DFP) and benzaldoxime as the nucleophile. Autoinductive fluoride amplification responds to fluoride released from DFP by amplifying the fluoride concentration and a yellow reporter molecule. The reporter is a conjugated oligomer with a nominal repeating unit that originates from 4-aminobenzaldehyde. Exposure of the amplified fluoride to a fluoride-specific ratiometric fluorescent reporter provides a fluorescent readout, in which three fluorophores are generated per fluoride. Both colorimetric and fluorescent readouts enable quantitative assays with low micromolar limits of detection for fluoride resulting from DFP. More importantly, this work demonstrates the successful merging of multiple complex reactions for achieving selective, sensitive, and quantitative chemosensing.

A Strategy for Minimizing Background Signal in Autoinductive Signal Amplification Reactions for Point-of-Need Assays.

Rapid point-of-need assays are used to detect abundant biomarkers. The development of in situ signal amplification reactions could extend these assays to screening and triaging of patients for trace levels of biomarkers, even in resource-limited settings. We, and others, have developed small molecule-based in situ signal amplification reactions that eventually may be useful in this context. Herein we describe a design strategy for minimizing background signal that may occur in the absence of the target analyte, thus moving this in situ signal amplification approach one step closer to practical applications. Specifically, we describe allylic ethers as privileged connectors for linking detection and propagating functionality in a small molecule signal amplification reagent. Allylic ethers minimize background reactions while still enabling controlled release of a propagating signal in order to continue the signal amplification reaction. This paper characterizes the ability of allylic ethers to provide an amplified response, and offers insight into additional design considerations that are needed before in situ small molecule-based signal amplification becomes a viable strategy for point-of-need diagnostics.

Design, Synthesis, and Characterization of Small-Molecule Reagents That Cooperatively Provide Dual Readouts for Triaging and, When Necessary, Quantifying Point-of-Need Enzyme Assays.

A newly designed small molecule reagent provides both qualitative and quantitative readouts in assays that detect enzyme biomarkers. The qualitative readout enables rapid triaging of samples so that only samples that contain relevant concentrations of the target analyte must be quantified. The reagent is accessible in essentially three steps and 34% overall yield, is stable as a solid when heated to 44 °C for >1 month, and does not produce background signal when used in an assay. This paper describes the design and synthesis of the reagent, characterizes its response properties, and establishes the scope of its reactivity.

Stimuli-Responsive Polymer Film that Autonomously Translates a Molecular Detection Event into a Macroscopic Change in Its Optical Properties via a Continuous, Thiol-Mediated Self-Propagating Reaction.

This Communication describes a chemically responsive polymer film that is capable of detecting low levels of a specific applied molecular signal (thiol) and subsequently initiating a self-propagating reaction within the material that converts the nonfluorescent film into a globally fluorescent material. We illustrate that the intensity of the resulting fluorescent material is independent of the quantity of the applied thiol, whereas the rate to reach the maximum level of signal is directly proportional to the quantity of the signal. In contrast, a control film, which lacks functionality for mediating the self-propagating reaction, provides a maximum change in fluorescence that is directly proportional to the quantity of the applied thiol. This level of nonamplified signal is 78% lower in intensity (when initiated with 100 µM of applied thiol) than is achieved when the material contains functionality that supports the self-powered, self-propagating amplification reaction.

Rapid, On-Command Debonding of Stimuli-Responsive Cross-Linked Adhesives by Continuous, Sequential Quinone Methide Elimination Reactions.

Adhesives that selectively debond from a surface by stimuli-induced head-to-tail continuous depolymerization of poly(benzyl ether) macro-cross-linkers within a poly(norbornene) matrix are described. Continuous head-to-tail depolymerization provides faster rates of response than can be achieved using a small-molecule cross-linker, as well as responses to lower stimulus concentrations. Shear-stress values for glass held together by the adhesive reach 0.51±0.10 MPa, whereas signal-induced depolymerization via quinone methide intermediates reduces the shear stress values to 0.05±0.02 MPa. Changing the length of the macro-cross-linkers alters the time required for debonding, and thus enables the programmed sequential release of specific layers in a glass composite material.

Self-Immolative Poly(4,5-dichlorophthalaldehyde) and its Applications in Multi-Stimuli-Responsive Macroscopic Plastics.

End-capped poly(4,5-dichlorophthalaldehyde) (PCl2PA), which is a new self-immolative CD(r) polymer with the unique capability of depolymerizing continuously and completely in the solid state when an end cap is cleaved from the polymer by reaction with a specific molecular signal, is described. End-capped poly(4,5-dichlorophthalaldehyde) is sufficiently stable to enable patterning of three-dimensional macroscopic polymeric materials by selective laser sintering. These unique materials are capable of 1) autonomously amplifying macroscopic changes in the material in response to specific molecular inputs, and 2) altering their responses depending on the identity of the applied signal. Thus, not only does end-capped PCl2PA provide new and unique capabilities compared to the small subset of existing CD(r) polymers, but it also provides access to a new class of stimuli-responsive materials.

Surface-accessible detection units in self-immolative polymers enable translation of selective molecular detection events into amplified responses in macroscopic, solid-state plastics.

This Communication describes a strategy for incorporating detection units onto each repeating unit of self-immolative CDr polymers. This strategy enables macroscopic plastics to respond quickly to specific applied molecular signals that react with the plastic at the solid-liquid interface between the plastic and surrounding fluid. The response is a signal-induced depolymerization reaction that is continuous and complete from the site of the reacted detection unit to the end of the polymer. Thus, this strategy retains the ability of CDr polymers to provide amplified responses via depolymerization while simultaneously enhancing the rate of response of CDr-based macroscopic plastics to specific applied signals. Depolymerizable poly(benzyl ethers) were used to demonstrate the strategy and now are capable of depolymerizing in the context of rigid, solid-state polymeric materials.

Quantitative point-of-care (POC) assays using measurements of time as the readout: a new type of readout for mHealth.

A paper-based microfluidic device was used to quantitatively detect active enzyme analytes in samples at mid to low femtomolar levels. The device uses a hydrophobic oligomer that controls the wetting properties of the paper within the device. When the target analyte is present within the sample, the oligomer depolymerizes, thus switching the paper to hydrophilic, allowing for the sample to wick through the device. Measuring the time for the sample to wick to a control region relative to an assay region within the device results in sensitive, quantitative measurements of the target enzyme (e.g., alkaline phosphatase or ß-D-galactosidase). This device requires the use of only a timer for quantifying a target analyte, and thus the platform may be appropriate for use in resource-limited environments, where access to expensive diagnostic equipment is limited. A smartphone with integrated application software (the software has yet to be developed) could be used for timing the assay and for relating the time measurement to the quantitative readout for the assay. In future versions of this assay, it should be possible to configure the smartphone to start and stop the time-based measurement to further simplify the assay for the user.

Polymeric materials that convert local fleeting signals into global macroscopic responses.

We report a general design strategy for creating polymeric materials that are capable of providing global, macroscopic changes in their properties in response to specific local and fleeting stimuli. In a proof-of-concept demonstration, a single polymer is used, yet it enables selective responses to specific stimuli, and then internally drives a macroscopic change in the material (even in locations not exposed to the stimulus), where the magnitude of change is independent of the intensity of the applied stimulus.

Adaptive use of bubble wrap for storing liquid samples and performing analytical assays.

This paper demonstrates that the gas-filled compartments in the packing material commonly called "bubble wrap" can be repurposed in resource-limited regions as containers to store liquid samples, and to perform bioanalyses. The bubbles of bubble wrap are easily filled by injecting the samples into them using a syringe with a needle or a pipet tip, and then sealing the hole with nail hardener. The bubbles are transparent in the visible range of the spectrum, and can be used as "cuvettes" for absorbance and fluorescence measurements. The interiors of these bubbles are sterile and allow storage of samples without the need for expensive sterilization equipment. The bubbles are also permeable to gases, and can be used to culture and store micro-organisms. By incorporating carbon electrodes, these bubbles can be used as electrochemical cells. This paper demonstrates the capabilities of the bubbles by culturing E. coli, growing C. elegans, measuring glucose and hemoglobin spectrophotometrically, and measuring ferrocyanide electrochemically, all within the bubbles.

Quantitative Fluorescence Assays Using a Self-Powered Paper-Based Microfluidic Device and a Camera-Equipped Cellular Phone.

Fluorescence assays often require specialized equipment and, therefore, are not easily implemented in resource-limited environments. Herein we describe a point-of-care assay strategy in which fluorescence in the visible region is used as a readout, while a camera-equipped cellular phone is used to capture the fluorescent response and quantify the assay. The fluorescence assay is made possible using a paper-based microfluidic device that contains an internal fluidic battery, a surface-mount LED, a 2-mm section of a clear straw as a cuvette, and an appropriately-designed small molecule reagent that transforms from weakly fluorescent to highly fluorescent when exposed to a specific enzyme biomarker. The resulting visible fluorescence is digitized by photographing the assay region using a camera-equipped cellular phone. The digital images are then quantified using image processing software to provide sensitive as well as quantitative results. In a model 30 min assay, the enzyme ß-D-galactosidase was measured quantitatively down to 700 pM levels. This Communication describes the design of these types of assays in paper-based microfluidic devices and characterizes the key parameters that affect the sensitivity and reproducibility of the technique.

The expanding role of paper in point-of-care diagnostics.

This editorial discusses the expanding role of paper as a platform on which to build new point-of-care assays, particularly those intended for use in resource-limited settings. Successful diagnostics for use in these environments require a low-cost platform (possibly paper) as well as new assay strategies, reagents and materials for achieving selectivity and sensitivity. Paper provides a common platform for bringing these components together and serves as a low-cost medium for prototyping new point-of-care assays.

A prototype point-of-use assay for measuring heavy metal contamination in water using time as a quantitative readout.

This Communication describes a prototype quantitative paper-based assay that simultaneously measures the levels of Pb(2+) and Hg(2+) in water. The assay requires only measurements of time to yield a quantitative readout, and the results are independent of sample volume, humidity, and sample viscosity.

Continuous Head-to-Tail Depolymerization: An Emerging Concept for Imparting Amplified Responses to Stimuli-Responsive Materials.

Polymers that depolymerize continuously and completely from head-to-tail when a reaction-based detection unit is cleaved from the polymer provide both selective and amplified responses, a rare combination, to stimuli-responsive polymeric materials. This Viewpoint contextualizes this new class of depolymerizable polymers and outlines the key areas for growth and innovation.

Point-of-care assay platform for quantifying active enzymes to femtomolar levels using measurements of time as the readout.

This Article describes a strategy for quantifying active enzyme analytes in a paper-based device by measuring the time for a reference region in the paper to turn green relative to an assay region. The assay requires a single step by the user, yet accounts for variations in sample volume, assay temperature, humidity, and contaminants in a sample that would otherwise prevent a quantitative measurement. The assay is capable of measuring enzymes in the low to mid femtomolar range with measurement times that range from ~30 s to ~15 min (lower measurement times correspond to lower quantities of the analyte). Different targets can be selected in the assay by changing a small molecule reagent within the paper-based device, and the sensitivity and dynamic range of the assays can be tuned easily by changing the composition and quantity of a signal amplification reagent or by modifying the configuration of the paper-based microfluidic device. By tuning these parameters, limits-of-detection for assays can be adjusted over an analyte concentration range of low femtomolar to low nanomolar, with dynamic ranges for the assays of at least 1 order of magnitude. Furthermore, the assay strategy is compatible with complex fluids such as serum.

Reagents and assay strategies for quantifying active enzyme analytes using a personal glucose meter.

This communication describes small molecule reagents and a rapid single-step assay for quantifying nanomolar levels of active enzyme analytes using a personal glucose meter.