Solubility and size of polymer nanoparticles

The solubility of polymer nanoparticles is a complex phenomenon dependent on solvent–solute and solute–solute interactions. Contrary to phase separation in standard polymerization reactions, which is a well established research area, the relationship between the solubility of polymer nanoparticles and the resulting diameter of the nanoparticles has been largely overlooked. Herein we demonstrate that the absolute size of polymer nanoparticles can be predicted (and controlled) by varying the relevant parameters of the polymerization conditions that influence the solubility and Flory parameter, χs, p. The position of the spinodal, associated with a given χs, p equivalent and determined with a simple thermodynamic model, allows an absolute value, Δχspinodal, to be applied in predicting polymer dimensions. The hydrodynamic diameter of particles at the primarily observed fraction was found to be dependent on D (nm) = −74Δχspinodal + 367 nm, where Δχspinodal must be positive for successful separation. Variation with total polymer fraction over a limited range can also be observed to follow a trend of approximately D (nm) = 173 ln[(xN)2 10−36/Δχspinodal] − 193 nm, thus giving a more general description of polymerization. We also assert the importance of separating spinodal-character phase separation from binodal-character phase separation in polymer nanoparticle synthesis. To the best of our knowledge this is the first successful Flory–Huggins based thermodynamic model of polymer nanoparticles, and should provide a useful guide to predictive design of future nanomaterial

Highly Efficient Abiotic Assay Formats for Methyl Parathion: Molecularly Imprinted Polymer Nanoparticle Assay as an Alternative to Enzyme-Linked Immunosorbent Assay

Enzyme-linked immunosorbent assay (ELISA) is a widely used standard method for sensitive detection of analytes of environmental, clinical, or biotechnological interest. However, ELISA has clear drawbacks related to the use of relatively unstable antibodies and enzyme conjugates and the need for several steps such as washing of nonbound conjugates and addition of dye reagents. Herein, we introduce a new completely abiotic assay where antibodies and enzymes are replaced with fluorescent molecularly imprinted polymer nanoparticles (nanoMIPs) and target-conjugated magnetic nanoparticles, which acted as both reporter probes and binding agents. The components of the molecularly imprinted polymer nanoparticle assay (MINA) are assembled in microtiter plates fitted with magnetic inserts. We have compared the performance of a new magnetic assay with molecularly imprinted polymer (MIP)-based ELISA for the detection of methyl parathion (MP). Both assays have shown high sensitivity toward allowing detection of MP at picomolar concentrations without any cross-reactivity against chlorpyriphos and fenthion. The fully abiotic assays were also proven to detect analyte in real samples such as tap water and milk. Unlike ELISA-based systems, the novel assay required no washing steps or addition of enzyme substrates, making it more user-friendly and suitable for high throughput screening

Nanoparticle-induced enhancement of cholinesterase activity in the presence of malathion: A potential nerve agent therapeutic

Organophosphate nerve agents are associated with assassination, terrorism and chemical warfare, but there has been slow progress in developing a broad-spectrum response to poisoning. For some nerve agents the oxime component of the therapy may not be effective, limiting the effectiveness of emergency treatment that is desperately needed. An alternative therapy may be possible based on accelerating enzyme (acetylcholinesterase) catalysis in unaffected adjacent enzymes. Herein we demonstrate a restoration of acetylcholinesterase activity in malathion-inhibited cell membrane preparations by the administration of functional nanoparticles. The molecularly imprinted polymer nanoparticles were designed to bind selectively to designated enzyme epitopes. Enzyme activity of membrane-bound acetylcholinesterase was measured in the presence of the organophosphate malathion and the selected nanoparticles. Enzymatic acceleration of the cholinesterase was observed at 162 ± 17 % the rate of erythrocyte ghosts without bound nanoparticles. This may restore sufficient acetylcholine hydrolysis to mitigate the effects of poisoning, offsetting the acetylcholine accumulation resulting from enzyme inhibition

Design and fabrication of a smart sensor using in silico epitope mapping and electro-responsive imprinted polymer nanoparticles for determination of insulin levels in human plasma

A robust and highly specific sensor based on electroactive molecularly imprinted polymer nanoparticles (nanoMIP) was developed. The nanoMIP tagged with a redox probe, combines both recognition and reporting capabilities. The developed nanoMIP replaces enzyme-mediator pairs used in traditional biosensors thus, offering enhanced molecular recognition for insulin, improving performance in complex biological samples, and yielding high stability. Also, most of existing sensors show poor performance after storage. To improve costs of the logistics and avoid the need of cold storage in the chain supply, we developed an alternative to biorecognition system that relies on nanoMIP. NanoMIP were computationally designed using “in-silico” insulin epitope mapping and synthesized by solid phase polymerisation. The characterisation of the polymer nanoparticles was performed by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform Infrared (FT-IR) and surface plasmon resonance (SPR). The electrochemical sensor was developed by chemical immobilisation of the nanoMIP on screen printed platinum electrodes. The insulin sensor displayed satisfactory performances and reproducible results (RSD = 4.2%; n = 30) using differential pulse voltammetry (DPV) in the clinically relevant concentration range from 50 to 2000 pM. The developed nanoMIP offers the advantage of large number of specific recognition sites with tailored geometry, as the resultant, the sensor showed high sensitivity and selectivity to insulin with a limit of detection (LOD) of 26 and 81 fM in buffer and human plasma, respectively, confirming the practical application for point of care monitoring. Moreover, the nanoMIP showed adequate storage stability of 168 days, demonstrating the robustness of sensor for several rounds of insulin analysis

Disposable paracetamol sensor based on electroactive molecularly imprinted polymer nanoparticles for plasma monitoring

A highly sensitive disposable electrochemical sensor for paracetamol was devised using electroactive molecularly imprinted polymers nanoparticles (nanoMIPs). NanoMIPs were prepared by solid-phase synthesis. Polymer composition included itaconic acid as a specific functional monomer and ferrocene as redox label, which confers electroactivity to the nanoparticles. NanoMIPs were characterised by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and scanning electron microscopy (SEM). Sensors were fabricated by covalent attachment of nanoMIPs on screen-printed carbon electrodes and then employed for electrochemical determination of paracetamol using differential pulse voltammetry (DPV). The sensor was successfully evaluated in spiked human plasma with recoveries at 94–108 % and presenting a sensitivity of 6.18 ± 0.22 μA mM−1. The limit of detection and limit of quantification for the sensor were found to be 50 μM and 167 μM, respectively, in a linear concentration range between 0.1 and 1 mM. High selectivity was demonstrated, with no interference found in the presence of caffeine, procainamide or ethyl 4-aminobenzoate. The sensors exhibited high reproducibility (RSD, 4.8 %), fast response time (∼8 s) and acceptable shelf life (90 days), confirming its suitability for point of care diagnostic applications

Integration of smart nanomaterials for highly selective disposable sensors and their forensic applications in amphetamine determination

Screening drugs on the street and biological samples pose a challenge to law enforcement agencies due to existing detection methods and instrument limitations. Herein we present a graphene-assisted molecularly imprinted polymer nanoparticle-based sensor for amphetamine. These nanoparticles are electroactive by incorporating ferrocene in their structure. These particles act as specific actuators in electrochemical sensors, and the presence of a ferrocene redox probe embedded in the structure allows the detection of non-electroactive amphetamine. In a control approach, nanoparticles were covalently immobilised onto electrochemical sensors by drop-casting using silanes. Alternatively, nanoparticles were immobilised employing 3D printing and a graphene ink composite. The electrochemical performance of both approaches was evaluated. As a result, 3D printed nanoMIPs/graphene sensors displayed the highest selectivity in spiked human plasma, with sensitivity at 73 nA nM−1, LOD of 68 nM (RSD 2.4%) when compared to the silane drop cast electrodes. The main advantage of the optimised 3D printing technology is that it allows quantitative determination of amphetamine, a non-electroactive drug, challenging to detect with conventional electrochemical sensors. In addition, the cost-efficient 3D printing method makes these sensors easy to manufacture, leading to robust, highly selective and sensitive sensors. As proof of concept, sensors were evaluated on the street specimens and clinically relevant samples and successfully validated using UPLC-MS