Noninvasive and Multiplex Self-Test of Kidney Disease Biomarkers with Graphene-Based Lab-on-a-Chip (G-LOC): Toward Digital Diagnostics in the Hands of Patients.

Chronic kidney disease is one of the major health issues worldwide. However, diagnosis is now highly centralized in large laboratories, resulting in low access to patient monitoring and poor personalized treatments. This work reports the development of a graphene-based lab-on-a-chip (G-LOC) for the digital testing of renal function biomarkers in serum and saliva samples. G-LOC integrates multiple bioelectronic sensors with a microfluidic system that enables multiplex self-testing of urea, potassium, sodium, and chloride. The linearity, limit of detection (LOD), accuracy, and coefficient of variability (CV) were studied. Accuracy values higher than 95.5% and CV lower than 9% were obtained for all of the biomarkers. The analytical performance was compared against three reference lab benchtop analyzers by measuring healthy- and renal-failure-level samples of serum. From receiver operating characteristic (ROC) plots, sensitivities (%) of 99.7, 97.6, 99.1, and 89.0 were obtained for urea, potassium, sodium, and chloride, respectively. Then, the test was evaluated in noninvasive saliva samples and compared against reference methods. Correlation and Bland-Altman plots showed good correlation and agreement of the G-LOC with the reference methods. It is noteworthy that the precision of G-LOC was similar to better than benchtop lab analyzers, with the advantage of being highly portable. Finally, a user testing study was conducted. The analytical performance obtained with untrained volunteers was similar to that obtained with trained chemists. Additionally, based on a user experience survey, G-LOC was found to have very simple usability and would be suitable for at-home diagnostics.

Polyelectrolyte-multivalent molecule complexes: physicochemical properties and applications.

The complexation of polyelectrolytes with other oppositely charged structures gives rise to a great variety of functional materials with potential applications in a wide spectrum of technological fields. Depending on the assembly conditions, polyelectrolyte complexes can acquire different macroscopic configurations such as dense precipitates, nanosized colloids and liquid coacervates. In the past 50 years, much progress has been achieved to understand the principles behind the phase separation induced by the interaction of two oppositely charged polyelectrolytes in aqueous solutions, especially for symmetric systems (systems in which both polyions have similar molecular weight and concentration). However, in recent years, the complexation of polyelectrolytes with alternative building blocks such as small charged molecules (multivalent inorganic species, oligopeptides, and oligoamines, among others) has gained attention in different areas. In this review, we discuss the physicochemical characteristics of the complexes formed by polyelectrolytes and multivalent small molecules, putting a special emphasis on their similarities with the well-known polycation-polyanion complexes. In addition, we analyze the potential of these complexes to act as versatile functional platforms in various technological fields, such as biomedicine and advanced materials engineering.

Field-effect transistors engineered via solution-based layer-by-layer nanoarchitectonics.

The layer-by-layer (LbL) technique has been proven to be one of the most versatile approaches in order to fabricate functional nanofilms. The use of simple and inexpensive procedures as well as the possibility to incorporate a very wide range of materials through different interactions have driven its application in a wide range of fields. On the other hand, field-effect transistors (FETs) are certainly among the most important elements in electronics. The ability to modulate the flowing current between a source and a drain electrode via the voltage applied to the gate electrode endow these devices to switch or amplify electronic signals, being vital in all of our everyday electronic devices. In this topical review, we highlight different research efforts to engineer field-effect transistors using the LbL assembly approach. We firstly discuss on the engineering of the channel material of transistors via the LbL technique. Next, the deposition of dielectric materials through this approach is reviewed, allowing the development of high-performance electronic components. Finally, the application of the LbL approach to fabricate FETs-based biosensing devices is also discussed, as well as the improvement of the transistor's interfacial sensitivity by the engineering of the semiconductor with polyelectrolyte multilayers.

The Effect of Amino-Phosphate Interactions on the Biosensing Performance of Enzymatic Graphene Field-Effect Transistors.

The interaction between polyamines and phosphate species is found in a wide range of biological and abiotic systems, yielding crucial consequences that range from the formation of supramolecular colloids to structure determination. In this work, the occurrence of phosphate-amino interactions is evidenced from changes in the electronic response of graphene field effect transistors (gFETs). First, the surface of the transistors is modified with poly(allylamine), and the effect of phosphate binding on the transfer characteristics is interpreted in terms of its impact on the surface charge density. The electronic response of the polyamine-functionalized gFETs is shown to be sensitive to the presence of different phosphate anions, such as orthophosphate, adenosine triphosphate, and tripolyphosphate, and a simple binding model is developed to explain the dependence of the shift of the Dirac point potential on the phosphate species concentration. Afterward, the impact of phosphate-amino interactions on the immobilization of enzymes to polyamine-modified graphene surfaces is investigated, and a decrease in the amount of anchored enzyme as the phosphate concentration increases is found. Finally, multilayer polyamine-urease biosensors are fabricated while increasing the phosphate concentration in the enzyme solution, and the sensing properties of the gFETs toward urea are evaluated. It is found that the presence of simple phosphate anions alters the nanoarchitecture of the polyelectrolyte-urease assemblies, with direct implications on urea sensing.

Insulin Delivery from Glucose-Responsive, Self-Assembled, Polyamine Nanoparticles: Smart "Sense-and-Treat" Nanocarriers Made Easy.

Polyamine-salt aggregates (PSA) are biomimetic soft materials that have attracted great attention due to their straightforward fabrication methods, high drug-loading efficiencies, and attractive properties for pH-triggered release. Herein, a simple and fast multicomponent self-assembly process was used to construct cross-linked poly(allylamine hydrochloride)/phosphate PSAs (hydrodynamic diameter of 360 nm) containing glucose oxidase enzyme, as a glucose-responsive element, and human recombinant insulin, as a therapeutic agent for the treatment of diabetes mellitus (GI-PSA). The addition of increasing glucose concentrations promotes the release of insulin due to the disassembly of the GI-PSAs triggered by the catalytic in situ formation of gluconic acid. Under normoglycemia, the GI-PSA integrity remained intact for at least 24 h, whereas hyperglycemic conditions resulted in 100 % cargo release after 4 h of glucose addition. This entirely supramolecular strategy presents great potential for the construction of smart glucose-responsive delivery nanocarriers.

Redox-active polyamine-salt aggregates as multistimuli-responsive soft nanoparticles.

Polyamine-salt aggregates have become promising soft materials in nanotechnology due to their easy preparation process and pH-responsiveness. Here, we report the use of hexacyanoferrate(ii) and hexacyanoferrate(iii) as electroactive crosslinking agents for the formation of nanometer-sized redox-active polyamine-redox-salt aggregates (rPSA) in bulk suspension. This nanoplatform can be selectively assembled or disassembled under different stimuli such as redox environment, pH and ionic strength. By changing the charge of the building blocks, external triggers allow switching the system between two phase states: aggregate-free solution or colloidal rPSA dispersion. The stimuli-activated modulation of the assembly/disassembly processes opens a path to exploit rPSA in technologies based on smart nanomaterials.

Practical use of polymer brushes in sustainable energy applications: interfacial nanoarchitectonics for high-efficiency devices.

The discovery and development of novel approaches, materials and manufacturing processes in the field of energy are compelling increasing recognition as a major challenge for contemporary societies. The performance and lifetime of energy devices are critically dependent on nanoscale interfacial phenomena. From the viewpoint of materials design, the improvement of current technologies inevitably relies on gaining control over the complex interface between dissimilar materials. In this sense, interfacial nanoarchitectonics with polymer brushes has seen growing interest due to its potential to overcome many of the limitations of energy storage and conversion devices. Polymer brushes offer a broad variety of resources to manipulate interfacial properties and gain molecular control over the synergistic combination of materials. Many recent examples show that the rational integration of polymer brushes in hybrid nanoarchitectures greatly improves the performance of energy devices in terms of power density, lifetime and stability. Seen in this light, polymer brushes provide a new perspective from which to consider the development of hybrid materials and devices with improved functionalities. The aim of this review is therefore to focus on what polymer brush-based solutions can offer and to show how the practical use of surface-grafted polymer layers can improve the performance and efficiency of fuel cells, lithium-ion batteries, organic radical batteries, supercapacitors, photoelectrochemical cells and photovoltaic devices.

Polyamine Colloids Cross-Linked with Phosphate Ions: Towards Understanding the Solution Phase Behavior.

Ionically crosslinked poly(allylamine)/phosphate (PAH/Pi) colloids consist of self-assembled nanostructures stabilized by supramolecular interactions. Under physiological conditions, these interactions should be present at high ionic strength and only in a narrow pH window to be effective as drug delivery agents. In this work we study the effect of the pH and ionic strength in the chemical behaviour of inorganic phosphate (Pi), poly(allylamine hydrochloride) (PAH) and their mixture in aqueous solution (PAH-Pi). By combination of experimental measurements and a theoretical model, we demonstrate that the driving force that leads to the formation of colloids is the electrostatic pairing between the positively charged amino groups in PAH and negatively charged HPO42- ions. Increasing the ionic strength of the system by addition of KCl weakens the PAH-Pi interactions and narrows the pH stability window from 4 to 1.8 pH units. In addition, a fully reversible system was obtained in which the colloids assemble and disassemble by changing the pH between 6.8 and 7.1 at high ionic strength, making them suitable for use as pH-responsive nanocarriers.

Continuous assembly of supramolecular polyamine-phosphate networks on surfaces: preparation and permeability properties of nanofilms.

Supramolecular self-assembly of molecular building blocks represents a powerful "nanoarchitectonic" tool to create new functional materials with molecular-level feature control. Here, we propose a simple method to create tunable phosphate/polyamine-based films on surfaces by successive assembly of poly(allylamine hydrochloride) (PAH)/phosphate anions (Pi) supramolecular networks. The growth of the films showed a great linearity and regularity with the number of steps. The coating thickness can be easily modulated by the bulk concentration of PAH and the deposition cycles. The PAH/Pi networks showed chemical stability between pH 4 and 10. The transport properties of the surface assemblies formed from different deposition cycles were evaluated electrochemically by using different redox probes in aqueous solution. The results revealed that either highly permeable films or efficient anion transport selectivity can be created by simply varying the concentration of PAH. This experimental evidence indicates that this new strategy of supramolecular self-assembly can be useful for the rational construction of single polyelectrolyte nanoarchitectures with multiple functionalities.

Phosphate-Responsive Biomimetic Nanofluidic Diodes Regulated by Polyamine-Phosphate Interactions: Insights into Their Functional Behavior from Theory and Experiment.

There is currently high interest in developing nanofluidic devices whose iontronic output is defined by biological interactions. The fabrication of a phosphate responsive nanofluidic diode by using the biological relevant amine-phosphate interactions is shown. The fabrication procedure includes the modification of a track-etched asymmetric (conical) nanochannel with polyallylamine (PAH) by electrostatic self-assembly. PAH is the arcaetypical model of polyamine and it is further used to address the nanochannels with phosphate responsivity. In order to explore the influence that phosphate in solution has in the conductance of the modified nanochannels, current-voltage measurements using different concentrations of phosphates are performed. Furthermore, to have a complete physicochemical understanding of the system, experimental data is analyzed using a continuous model based on Poison-Nernst-Planck equations and compared with results obtained from stochastic Monte Carlo simulations.

Proton-Gated Rectification Regimes in Nanofluidic Diodes Switched by Chemical Effectors.

During the last decade, nanofluidic devices based on solid-state nanopores and nanochannels have come into scene in materials science and will not leave anytime soon. One of the main reasons for this is the excellent control over ionic transport exerted by such devices that promises further important advances when integrated into more complex molecular devices. As a result, pH, temperature, and voltage-regulated devices have been obtained. However, nowadays, there is still a necessity for molecule-driven nanofluidic devices. Here, a sugar-regulated pH-responsive nanofluidic diode is presented obtained by surface modification of conical polycarbonate nanochannels with electropolymerized 3-aminophenylboronic acid. Control over the ionic transport has been achieved by a successful decoration of asymmetric nanochannels with integrated molecular systems. The as-synthesized boronate-appended zwitterionic polymer exhibits an acid-base equilibrium that depends on the concentration of sugar, which ultimately acts as a chemical effector setting different pH-dependent rectification regimes. As a result, the same nanodevice can perform completely different proton-regulated nanofluidic operations, i.e., anion-driven rectification, cation-driven rectification, and no rectification, by simply varying the concentration of fructose in the electrolyte solution.

Highly-organized stacked multilayers via layer-by-layer assembly of lipid-like surfactants and polyelectrolytes. Stratified supramolecular structures for (bio)electrochemical nanoarchitectonics.

Supramolecular self-assembly is of paramount importance for the development of novel functional materials with molecular-level feature control. In particular, the interest in creating well-defined stratified multilayers through simple methods using readily available building blocks is motivated by a multitude of research activities in the field of "nanoarchitectonics" as well as evolving technological applications. Herein, we report on the facile preparation and application of highly organized stacked multilayers via layer-by-layer assembly of lipid-like surfactants and polyelectrolytes. Polyelectrolyte multilayers with high degree of stratification of the internal structure were constructed through consecutive assembly of polyallylamine and dodecyl phosphate, a lipid-like surfactant that act as a structure-directing agent. We show that multilayers form well-defined lamellar hydrophilic/hydrophobic domains oriented parallel to the substrate. More important, X-ray reflectivity characterization conclusively revealed the presence of Bragg peaks up to fourth order, evidencing the highly stratified structure of the multilayer. Additionally, hydrophobic lamellar domains were used as hosts for ferrocene in order to create an electrochemically active film displaying spatially-addressed redox units. Stacked multilayers were then assembled integrating redox-tagged polyallylamine and glucose oxidase into the stratified hydrophilic domains. Bioelectrocatalysis and "redox wiring" in the presence of glucose was demonstrated to occur inside the stratified multilayer.

Electrochemical nanoarchitectonics through polyaminobenzylamine-dodecyl phosphate complexes: redox activity and mesoscopic organization in self-assembled nanofilms.

Molecular design and preparation of redox active films displaying mesoscopic levels of organization represents one of the most actively pursued research areas in nanochemistry. These mesostructured materials are not only of great interest at the fundamental level because of their unique properties but they can also be employed for a wide range of applications such as electrocatalysts, electronic devices, and electrochemical energy conversion and storage. Herein, we introduce a simple and straightforward strategy to chemically modify electrode surfaces with self-assembled electroactive polyelectrolyte-surfactant complexes. These assemblies are composed of amino-appended polyaniline and monododecyl phosphate. The complexes were deposited by spin-coating and the films were characterized by spectroscopic and X-ray-based techniques: XRR, GISAXS, WAXS, and XPS. The films presented a well-defined lamellar structure, directed by the strong interaction between the phosphate groups and the positively charged amine groups in the polyelectrolyte. These films also displayed intrinsic electroactivity in both acidic and neutral solutions, showing that the polymer remains electroactive and ionic transport is still possible through the stratified and hydrophobic coatings. The stability and enhanced electroactivity in neutral solutions make these assembled films promising building blocks for the construction of nanostructured electrochemical platforms.

Dangerous liaisons: anion-induced protonation in phosphate-polyamine interactions and their implications for the charge states of biologically relevant surfaces.

Although not always considered a preponderant interaction, amine-phosphate interactions are omnipresent in multiple chemical and biological systems. This study aims to answer questions that are still pending about their nature and consequences. We focus on the description of the charge state as surface charges constitute directing agents of the interaction of amine groups with either natural or synthetic counterparts. Our results allow us to quantitatively determine the relative affinities of HPO42- and H2PO4- from the analysis of the influence of phosphates on the zeta-potential of amino-functionalized surfaces in a broad pH range. We show that phosphate anions enhance the protonation of amino groups and, conversely, charged amines induce further proton dissociation of phosphates, yielding a complex dependence of the surface effective charge on the pH and phosphate concentration. We also demonstrate that phosphate-amine interaction is specific and the modulation of surface charge occurs in the physiological phosphate concentration range, emphasizing its biochemical and biotechnological relevance and the importance of considering this veiled association in both in vivo and in vitro studies.

Nanofluidic Diodes with Dynamic Rectification Properties Stemming from Reversible Electrochemical Conversions in Conducting Polymers.

The use of solid state nanochannels as nanofluidic diodes is currently a topic of large interest in nanotechnology. Particularly, there is a focus in the development of nanochannels with surface functionalities that make them responsive to multiple environmental variables. Here, we present for the first time the construction of electrochemical potential- and pH-responsive nanofluidic diodes using a novel approach based on a controlled electrochemical polymerization of aniline on gold-coated polycarbonate asymmetric nanochannels. The polyaniline-modified nanochannels showed three different levels of reversible ionic rectification corresponding to the degrees of oxidation of the conducting polymer. Our results demonstrate that this strategy enables an accurate and reversible control of the rectification properties due to the well-defined and predictable electrochemical conversion of charged species generated on the pore walls. We envision that these results will create novel avenues to fabricate electrochemically modulated nanofluidic diodes using conducting polymers integrated into single conical nanopores.

Effect of gold nanoparticles on the structure and electron-transfer characteristics of glucose oxidase redox polyelectrolyte-surfactant complexes.

Efficient electrical communication between redox proteins and electrodes is a critical issue in the operation and development of amperometric biosensors. The present study explores the advantages of a nanostructured redox-active polyelectrolyte-surfactant complex containing [Os(bpy)2Clpy](2+) (bpy=2,2'-bipyridine, py= pyridine) as the redox centers and gold nanoparticles (AuNPs) as nanodomains for boosting the electron-transfer propagation throughout the assembled film in the presence of glucose oxidase (GOx). Film structure was characterized by grazing-incidence small-angle X-ray scattering (GISAXS) and atomic force microscopy (AFM), GOx incorporation was followed by surface plasmon resonance (SPR) and quartz-crystal microbalance with dissipation (QCM-D), whereas Raman spectroelectrochemistry and electrochemical studies confirmed the ability of the entrapped gold nanoparticles to enhance the electron-transfer processes between the enzyme and the electrode surface. Our results show that nanocomposite films exhibit five-fold increase in current response to glucose compared with analogous supramolecular AuNP-free films. The introduction of colloidal gold promotes drastic mesostructural changes in the film, which in turn leads to a rigid, amorphous interfacial architecture where nanoparticles, redox centers, and GOx remain in close proximity, thus improving the electron-transfer process.

Manipulating Ion Transport Regimes in Nanomembranes via a "Pore-in-Pore" Approach Enabled by the Synergy of Metal-Organic Frameworks and Solid-State Nanochannels.

Solid-state nanochannels (SSNs) have emerged as promising platforms for controlling ionic transport at the nanoscale. SSNs are highly versatile, and this feature can be enhanced through their combination with porous materials such as Metal-Organic Frameworks (MOF). By selection of specific building blocks and experimental conditions, different MOF architectures can be obtained, and this can influence the ionic transport properties through the nanochannel. Herein, we study the effects of confined synthesis of Zr-based UiO-66 MOF on the ion transport properties of single bullet-shaped poly(ethylene terephthalate) (PET) nanochannels. We have found that emerging textural properties from the MOF phase play a determinant role in controlling ionic transport through the nanochannel. We demonstrate that a transition from ion current saturation regimes to diode-like regimes can be obtained by employing different synthetic approaches, namely, counterdiffusion synthesis, where MOF precursors are kept separate and forced to diffuse through the nanochannel, and one-pot synthesis, where both precursors are placed at both ends of the channel. Also, by considering the dependence of the charge state of the UiO-66 MOF on the protonation degree, pH changes offered a mechanism to tune the iontronic output (and selectivity) among different regimes, including anion-driven rectification, cation-driven rectification, ion current saturation, and ohmic behavior. Furthermore, Poisson-Nernst-Planck (PNP) simulations were employed to rationalize the different iontronic outputs observed experimentally for membranes modified by different methods. Our results demonstrate a straightforward tool to synthesize MOF-based SSN membranes with tunable ion transport regimes.

Insight into the transport of ions from salts of moderated solubility through nanochannels: negative incremental resistance assisted by geometry.

In this study, the transport of salt with moderate solubility through bioinspired solid-state nanochannels was comprehensively investigated. For this purpose, bullet-shaped channels were fabricated and exposed to KClO4, a monovalent salt with moderate solubility. These channels displayed the typical rectifying behavior characteristic of asymmetrical channels but with one remarkable difference, the iontronic output exhibited a negative incremental resistance phenomenon of high gating efficiency when the transmembrane voltage in the open state was increased enough, giving rise to an inactivated state characterized by a low and stable ion current. The behavior is attributed to salt precipitation inside the channel and remarkably, it is not observed in other geometries such as cylindrical or cigar-shaped channels. Considering the central role of the surface in precipitation formation, the influence of several parameters such as electrolyte concentration, pH, and channel size was studied. Under optimized conditions, this system can alternate among three different conductance states (closed, open, and inactivated) and exhibits gating ratios higher than 20. Beyond its potential application in fields related to electronics or sensing, this study provides valuable insight into the fundamental principles behind ion rectifying behavior in solid-state channels and highlights the implications of surface phenomena at the nanoscale.

Self-assembled monolayers of NH2-terminated thiolates: order, pKa, and specific adsorption.

Self-assembled monolayers (SAMs) of amino-terminated alkanethiols on Au were characterized by a combination of electrochemical (LSV, CV, and EIS) and spectroscopic (XPS and SER) techniques. Clear correlations were obtained between the apparent surface pKa values determined by impedimetric titrations and order parameters such as the content of trans conformers in the SAMs. These results contrast with previous studies that exhibit dispersions of up to 6 pH units in the reported pKa values. In addition, we determined that inorganic and organic phosphate species bind specifically to these SAMs mediating adsorption and heterogeneous electron transfer of positively charged macromolecules such as cytochrome c.

Phosphate mediated adsorption and electron transfer of cytochrome c. A time-resolved SERR spectroelectrochemical study.

The study of proteins immobilized on biomimetic or biocompatible electrodes represents an active field of research as it pursues both fundamental and technological interests. In this context, adsorption and redox properties of cytochrome c (Cyt) on different electrode surfaces have been extensively reported, although in some cases with contradictory results. Here we report a SERR spectroelectrochemical study of the adsorption and electron transfer behaviour of the basic protein Cyt on electrodes coated with amino-terminated monolayers. The obtained results show that inorganic phosphate (Pi) and ATP anions are able to mediate high affinity binding of the protein with preservation of the native structure and rendering an average orientation that guarantees efficient pathways for direct electron transfer. These findings aid the design of Cyt-based bioelectronic devices and understanding the modulation by Pi and ATP of physiological functions of Cyt.