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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.
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Grafite , Nefropatias , Humanos , Cloretos , Autoteste , Dispositivos Lab-On-A-Chip , Rim , Nefropatias/diagnóstico , Biomarcadores , Ureia , Potássio , SódioRESUMO
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.
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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.
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Alilamina , Técnicas Biossensoriais , Grafite , Trifosfato de Adenosina , Ânions , Grafite/química , Fosfatos , Poliaminas , Polieletrólitos , Transistores Eletrônicos , Ureia , Urease/químicaRESUMO
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 360â 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 24â h, whereas hyperglycemic conditions resulted in 100 % cargo release after 4â h of glucose addition. This entirely supramolecular strategy presents great potential for the construction of smart glucose-responsive delivery nanocarriers.
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Sistemas de Liberação de Medicamentos , Glucose/química , Insulina/administração & dosagem , Insulina/química , Nanocápsulas/química , Poliaminas/química , Reagentes de Ligações Cruzadas/química , Diabetes Mellitus/tratamento farmacológico , Gluconatos/química , Humanos , Insulina/farmacologiaRESUMO
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.
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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.
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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 1.8â 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.
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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.
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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.
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Biomimética/métodos , Fosfatos/química , Poliaminas/química , Método de Monte CarloRESUMO
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.
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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.
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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.
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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.
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Ânions/química , Fosfatos/química , Poliaminas/química , Concentração de Íons de Hidrogênio , PrótonsRESUMO
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.
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Herein, we present a novel approach to quantify ferritin based on the integration of an Enzyme-Linked Immunosorbent Assay (ELISA) protocol on a Graphene Field-Effect Transistor (gFET) for bioelectronic immunosensing. The G-ELISA strategy takes advantage of the gFET inherent capability of detecting pH changes for the amplification of ferritin detection using urease as a reporter enzyme, which catalyzes the hydrolysis of urea generating a local pH increment. A portable field-effect transistor reader and electrolyte-gated gFET arrangement are employed, enabling their operation in aqueous conditions at low potentials, which is crucial for effective biological sample detection. The graphene surface is functionalized with monoclonal anti-ferritin antibodies, along with an antifouling agent, to enhance the assay specificity and sensitivity. Markedly, G-ELISA exhibits outstanding sensing performance, reaching a lower limit of detection (LOD) and higher sensitivity in ferritin quantification than unamplified gFETs. Additionally, they offer rapid detection, capable of measuring ferritin concentrations in approximately 50 min. Because of the capacity of transistor miniaturization, our innovative G-ELISA approach holds promise for the portable bioelectronic detection of multiple biomarkers using a small amount of the sample, which would be a great advancement in point-of-care testing.
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Técnicas Biossensoriais , Ensaio de Imunoadsorção Enzimática , Ferritinas , Grafite , Transistores Eletrônicos , Ferritinas/análise , Grafite/química , Limite de Detecção , HumanosRESUMO
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.
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Compostos de Sulfidrila/síntese química , Adsorção , Alcanos/química , Citocromos c/química , Citocromos c/metabolismo , Transporte de Elétrons , Ouro/química , Concentração de Íons de Hidrogênio , Compostos de Sulfidrila/química , Propriedades de SuperfícieRESUMO
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.
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Citocromos c/metabolismo , Fosfatos/química , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Adsorção , Citocromos c/química , Técnicas Eletroquímicas , Eletrodos , Transporte de Elétrons , Elétrons , Cinética , Oxirredução , Estrutura Terciária de Proteína , Análise Espectral Raman , Fatores de TempoRESUMO
The fabrication of efficient organic electrochemical transistors (OECTs)-based biosensors requires the design of biocompatible interfaces for the immobilization of biorecognition elements, as well as the development of robust channel materials to enable the transduction of the biochemical event into a reliable electrical signal. In this work, PEDOT-polyamine blends are shown as versatile organic films that can act as both highly conducting channels of the transistors and non-denaturing platforms for the construction of the biomolecular architectures that operate as sensing surfaces. To achieve this goal, we synthesized and characterized films of PEDOT and polyallylamine hydrochloride (PAH) and employed them as conducting channels in the construction of OECTs. Next, we studied the response of the obtained devices to protein adsorption, using glucose oxidase (GOx) as a model system, through two different strategies: The direct electrostatic adsorption of GOx on the PEDOT-PAH film and the specific recognition of the protein by a lectin attached to the surface. Firstly, we used surface plasmon resonance to monitor the adsorption of the proteins and the stability of the assemblies on PEDOT-PAH films. Then, we monitored the same processes with the OECT showing the capability of the device to perform the detection of the protein binding process in real time. In addition, the sensing mechanisms enabling the monitoring of the adsorption process with the OECTs for the two strategies are discussed.
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Técnicas Biossensoriais , Polímeros , Ligação Proteica , Polímeros/química , Glucose Oxidase/química , PoliaminasRESUMO
Organic electrochemical transistors (OECTs) are important devices for the development of flexible and wearable sensors due to their flexibility, low power consumption, sensitivity, selectivity, ease of fabrication, and compatibility with other flexible materials. These features enable the creation of comfortable, versatile, and efficient portable devices that can monitor and detect a wide range of parameters for various applications. Herein, we present OECTs based on PEDOT-polyamine thin films for the selective monitoring of phosphate-containing compounds. Our findings reveal that supramolecular single phosphate-amino interaction induces higher changes in the OECT response compared to ATP-amino interactions, even at submillimolar concentrations. The steric character of binding anions plays a crucial role in OECT sensing, resulting in a smaller shift in maximum transconductance voltage and threshold voltage for bulkier binding species. The OECT response reflects not only the polymer/solution interface but also events within the conducting polymer film, where ion transport and concentration are affected by the ion size. Additionally, the investigation of enzyme immobilization reveals the influence of phosphate species on the assembly behavior of acetylcholinesterase (AchE) on PEDOT-PAH OECTs, with increasing phosphate concentrations leading to reduced enzyme anchoring. These findings contribute to the understanding of the mechanisms of OECT sensing and highlight the importance of careful design and optimization of the biosensor interface construction for diverse sensing applications.
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"Clickable" organic electrochemical transistors (OECTs) allow the reliable and straightforward functionalization of electronic devices through the well-known click chemistry toolbox. In this work, we study various aspects of the click chemistry-based interface engineering of "clickable" OECTs. First, different channel architectures are investigated, showing that PEDOT-N3 films can properly work as a channel of the transistors. Furthermore, the Cu(I)-catalyzed click reaction of ethynyl-ferrocene is studied under different reaction conditions, endowing the spatial control of the functionalization. The strain-promoted and catalyst-free cycloaddition of a dibenzocyclooctyne-derivatized poly-l-lysine (PLL-DBCO) is also performed on the OECTs and validated by a fiber optic (FO)-SPR setup. The further immobilization of an azido-modified HD22 aptamer yields OECT-based biosensors that are employed for the recognition of thrombin. Finally, their performance is evaluated against previously reported architectures, showing higher density of the immobilized HD22 aptamer, and originating similar KD values and higher maximum signal change upon analyte recognition.