Conformational Transition of Semiflexible Ring Polyelectrolyte in Tetravalent Salt Solutions: A Simple Numerical Modeling without the Effect of Twisting.

In this work, the conformational behaviors of ring polyelectrolyte in tetravalent salt solutions are discussed in detail through molecular dynamics simulation. For simplification, here we have neglected the effect of the twisting interaction, although it has been well known that both bending and twisting interactions play a deterministic in the steric conformation of a semiflexible ring polymer. The salt concentration CS and the bending energy b take a decisive role in the conformation of the ring polyelectrolyte (PE). Throughout our calculations, the b varies from b = 0 (freely joint chain) to b = 120. The salt concentration CS changes in the range of 3.56 × 10-4 M ≤ CS ≤ 2.49 × 10-1 M. Upon the addition of salt, ring PE contracts at first, subsequently re-expands. More abundant conformations are observed for a semiflexible ring PE. For b = 10, the conformation of semiflexible ring PE shifts from the loop to two-racquet-head spindle, then it condenses into toroid, finally arranges into coil with the increase of CS. As b increases further, four phase transitions are observed. The latter two phase transitions are different. The semiflexible ring PE experiences transformation from toroid to two racquet head spindle, finally to loop in the latter two phase transitions. Its conformation is determined by the competition among the bending energy, cation-bridge, and entropy. Combined, our findings indicate that the conformations of semiflexible ring PE can be controlled by changing the salt concentration and chain stiffness.

Polymerization mechanism of the Candida albicans virulence factor candidalysin.

Candida albicans is a commensal fungus that can cause epithelial infections and life-threatening invasive candidiasis. The fungus secretes candidalysin (CL), a peptide that causes cell damage and immune activation by permeation of epithelial membranes. The mechanism of CL action involves strong peptide assembly into polymers in solution. The free ends of linear CL polymers can join, forming loops that become pores upon binding to membranes. CL polymers constitute a therapeutic target for candidiasis, but little is known about CL self-assembly in solution. Here, we examine the assembly mechanism of CL in the absence of membranes using complementary biophysical tools, including a new fluorescence polymerization assay, mass photometry, and atomic force microscopy. We observed that CL assembly is slow, as tracked with the fluorescent marker C-laurdan. Single-molecule methods showed that CL polymerization involves a convolution of four processes. Self-assembly begins with the formation of a basic subunit, thought to be a CL octamer that is the polymer seed. Polymerization proceeds via the addition of octamers, and as polymers grow they can curve and form loops. Alternatively, secondary polymerization can occur and cause branching. Interplay between the different rates determines the distribution of CL particle types, indicating a kinetic control mechanism. This work elucidates key physical attributes underlying CL self-assembly which may eventually evoke pharmaceutical development.

Addressing Signal Drift and Screening for Detection of Biomarkers with Carbon Nanotube Transistors.

Electrical biosensors, including transistor-based devices (i.e., BioFETs), have the potential to offer versatile biomarker detection in a simple, low-cost, scalable, and point-of-care manner. Semiconducting carbon nanotubes (CNTs) are among the most explored nanomaterial candidates for BioFETs due to their high electrical sensitivity and compatibility with diverse fabrication approaches. However, when operating in solutions at biologically relevant ionic strengths, CNT-based BioFETs suffer from debilitating levels of signal drift and charge screening, which are often unaccounted for or sidestepped (but not addressed) by testing in diluted solutions. In this work, we present an ultrasensitive CNT-based BioFET called the D4-TFT, an immunoassay with an electrical readout, which overcomes charge screening and drift-related limitations of BioFETs. In high ionic strength solution (1X PBS), the D4-TFT repeatedly and stably detects subfemtomolar biomarker concentrations in a point-of-care form factor by increasing the sensing distance in solution (Debye length) and mitigating signal drift effects. Debye length screening and biofouling effects are overcome using a poly(ethylene glycol)-like polymer brush interface (POEGMA) above the device into which antibodies are printed. Simultaneous testing of a control device having no antibodies printed over the CNT channel confirms successful detection of the target biomarker via an on-current shift caused by antibody sandwich formation. Drift in the target signal is mitigated by a combination of: (1) maximizing sensitivity by appropriate passivation alongside the polymer brush coating; (2) using a stable electrical testing configuration; and (3) enforcing a rigorous testing methodology that relies on infrequent DC sweeps rather than static or AC measurements. These improvements are realized in a relatively simple device using printed CNTs and antibodies for a low-cost, versatile platform for the ongoing pursuit of point-of-care BioFETs.

Unraveling the Microscopic Mechanism of Molecular Ion Interaction with Monoclonal Antibodies: Impact on Protein Aggregation.

Understanding and predicting protein aggregation represents one of the major challenges in accelerating the pharmaceutical development of protein therapeutics. In addition to maintaining the solution pH, buffers influence both monoclonal antibody (mAb) aggregation in solution and the aggregation mechanisms since the latter depend on the protein charge. Molecular-level insight is necessary to understand the relationship between the buffer-mAb interaction and mAb aggregation. Here, we use all-atom molecular dynamics simulations to investigate the interaction of phosphate (Phos) and citrate (Cit) buffer ions with the Fab and Fc domains of mAb COE3. We demonstrate that Phos and Cit ions feature binding mechanisms, with the protein that are very different from those reported previously for histidine (His). These differences are reflected in distinctive ion-protein binding modes and adsorption/desorption kinetics of the buffer molecules from the mAb surface and result in dissimilar effects of these buffer species on mAb aggregation. While His shows significant affinity toward hydrophobic amino acids on the protein surface, Phos and Cit ions preferentially bind to charged amino acids. We also show that Phos and Cit anions provide bridging contacts between basic amino acids in neighboring proteins. The implications of such contacts and their connection to mAb aggregation in therapeutic formulations are discussed.

Label-Free Neuropeptide Detection beyond the Debye Length Limit.

Biosensors with high selectivity, high sensitivity, and real-time detection capabilities are of significant interest for diagnostic applications as well as human health and performance monitoring. Graphene field-effect transistor (GFET) based biosensors are suitable for integration into wearable sensor technology and can potentially demonstrate the sensitivity and selectivity necessary for real-time detection and monitoring of biomarkers. Previously reported DC-mode GFET biosensors showed a high sensitivity for sensing biomarkers in solutions with a low salt concentration. However, due to Debye length screening, the sensitivity of the DC-mode GFET biosensors decreases significantly during operation in a physiological fluid such as sweat or interstitial fluid. To overcome the Debye screening length limitation, we report here alternating current (AC) mode heterodyne-based GFET biosensors for sensing neuropeptide-Y (NPY), a key stress biomarker, in artificial sweat at physiologically relevant ionic concentrations. Our AC-mode GFET biosensors show a record ultralow detection limit of 2 × 10-18 M with an extensive dynamic range of 10 orders of magnitude in sensor response to target NPY concentration. The sensors were characterized for various carrier frequencies (ranging from 30 kHz to 2 MHz) of the applied AC voltages and various salt concentrations (10, 50, and 100 mM). Contrary to DC-mode sensing, the AC-mode sensor response increases with an increase in salt concentration in the electrolyte. The sensor response can be further enhanced by tuning the carrier frequency of the applied AC voltage. The optimum response frequency of our sensor is approximately 400-600 kHz for salt concentrations of 50 and 100 mM, respectively. The salt-concentration- and frequency-dependent sensor response can be explained by an electrolyte-gated capacitance model.

ZnO tetrapod morphology influence on UV sensing properties.

The aim of this work was to investigate how ZnO tetrapod (ZnO-T) morphology, structure, and surface charge properties (i.e. Debye length) influence their UV sensing properties, shedding light on the underlying photoresponse mechanisms. ZnO-Ts were synthesized and centrifuged to obtain three different fractions with tuned morphology, which were characterized by scanning electron microscopy, transmission electron microscopy, and high-resolution transmission electron microscopy microscopies, x-ray diffraction analysis, Brunauer-Emmett-Teller measurements, FTIR and UV-vis spectroscopies. ZnO-T UV sensors were fabricated and tested comparing among ZnO-T fractions and commercial ZnO nanoparticles. ZnO-T photoresponse was mostly influenced by ZnO-T leg diameter, with the optimal value close to the double Debye length. We also demonstrated how fractionating ZnO-Ts for morphology optimization can increased the responsivity by 2 orders of magnitude. Moreover, ZnO-T showed 3 orders of magnitude higher responsivity compared to commercial ZnO nanopowder. These results are beneficial for the engineering of efficient UV sensors and contribute to a deeper understanding the overall mechanism governing UV photoresponse.

Effect of electrodialysis on colloidal geometry and dynamics: Why my membrane stack was clogged even after a fine pretreatment?

As a long-standing problem, electrodialysis (ED) clogging is believed a consequence of colloids. However, its blocking causation and clogging mechanism have not been verified. In this study, electrodialysis was used to treat a colloidal saline solution, aiming to answer the question from the "nature" of ED by investigating the influence of ED parameters such as laminar flow, salt concentration, current density and pH on colloid geometry and dynamics during the desalting process. The results revealed that: (i) laminar and membrane electrostatic repulsion and adsorption could not significantly increase the particle size (maximum 2.28 times), while the applied electric field elevated the particle size by 54.52 times (119.9 ± 13.66 to 6537.5 ± 64.35 nm); (ii) when the initial feed concentration elevated 10 times (0.1 to 1 mol/L NaCl), the particle size upsurged 149-fold (5.99 ± 0.57 to >150 µm), and flocs were generated. This enhancement was mainly attributed to the compressive electric double layer effect, and the Debye length was trimmed from 0.96 to 0.30 nm; (iii) The low current density (25 A/m2) had a profound aggregation effect on small BSA particles (roughly 10 nm); (iv) The change of pH causes the conformational transition of BSA. In the strong acidic (pH = 3.0) environment, the colloidal particle size expanded by 13 times. This study confirmed that the aggregation of colloids was the culprit of spacer clogging during electrodialysis at higher salt concentrations (>1 mol/L). Furthermore, experimental data were substituted into the simulation formula to summarise the geometry and dynamic variation of BSA in ED.

Sybodies as Novel Bioreceptors toward Field-Effect Transistor-Based Detection of SARS-CoV-2 Antigens.

The SARS-CoV-2 pandemic has increased the demand for low-cost, portable, and rapid biosensors, driving huge research efforts toward new nanomaterial-based approaches with high sensitivity. Many of them employ antibodies as bioreceptors, which have a costly development process that requires animal facilities. Recently, sybodies emerged as a new alternative class of synthetic binders and receptors with high antigen binding efficiency, improved chemical stability, and lower production costs via animal-free methods. Their smaller size is an important asset to consider in combination with ultrasensitive field-effect transistors (FETs) as transducers, which respond more intensely when biorecognition occurs near their surface. This work demonstrates the immobilization of sybodies against the spike protein of the virus on silicon surfaces, which are often integral parts of the semiconducting channel of FETs. Immobilized sybodies maintain the capability to capture antigens, even at low concentrations in the femtomolar range, as observed by fluorescence microscopy. Finally, the first proof of concept of sybody-modified FET sensing is provided using a nanoscopic silicon net as the sensitive area where the sybodies are immobilized. The future development of further sybodies against other biomarkers and their generalization in biosensors could be critical to decrease the cost of biodetection platforms in future pandemics.

In-Operando Optical Spectroscopy of Field-Effect-Gated Al-Doped ZnO.

Transparent conductive oxides (TCO) have the unique characteristics of combining optical transparency with high electrical conductivity; such a property makes them uniquely alluring for applications in visible and infrared photonics. One of their most interesting features is the large sensitivity of their optical response to the doping level. We performed the active electrical manipulation of the dielectric properties of aluminum-doped ZnO (AZO), a TCO-based on Earth-abundant elements. We actively tuned the optical and electric performances of AZO films by means of an applied voltage in a parallel-plate capacitor configuration, with SrTiO3 as the dielectric, and monitored the effect of charge injection/depletion by means of in-operando spectroscopic ellipsometry. Calculations of the optical response of the gated system allowed us to extract the spatially resolved variations in the dielectric function of the TCO and infer the injected/depleted charge profile at the interface.

Effect of Back-Channel Surface on Reliability of Solution-Processed In0.51Ga0.15Zn0.34O Thin-Film Transistors with Thin Active Layer.

We have investigated the degradation mechanism of solution-processed indium-gallium-zinc-oxide (IGZO) thin-film transistors. The threshold voltage shift (ΔVth) followed a linear function under negative gate bias stress (NBS), while it showed a stretched-exponential behavior under positive gate bias stress. The slope of ΔVth for stress time was rarely changed with variations below 0.3 mV/s. The thickness of the fabricated IGZO layer (In0.51Ga0.15Zn0.34O) was approximately 10 nm. The Debye length (LD) was larger than IGZO thickness (tIGZO) due to the fully depleted active layer under NBS. Therefore, the degradation phenomenon under NBS was related to the adsorption at back-channel surface. The back-channel surface could be affected by the gate bias under NBS, and the molecules adsorbed at the IGZO layer were positively charged and induced extra electrons by NBS. We verified that the number of positively charged adsorbates had a proportional relationship with the ΔVth based on the two-dimensional technology computer-aided design (TCAD) simulation. Furthermore, we investigated the degradation phenomenon with the ΔVth equation regarding the adsorbates, and the result confirmed that the adsorption process could cause the linear ΔVth. We experimentally confirmed the effect of back-channel surface by comparing the ΔVth between different atmospheric conditions and LD. Consequently, the reaction at the back-channel surface should be considered to develop the metal-oxide semiconductor devices.

Interaction Energy between Two Separated Charged Spheres Surrounded Inside and Outside by Electrolyte.

By using the recently generalized version of Newton's shell theorem, analytical equations are derived to calculate the electric interaction energy between two separated, charged spheres surrounded outside and inside by electrolyte. This electric interaction energy is calculated as a function of the electrolyte's ion concentration, temperature, distance between the spheres and size of the spheres. At the same distance between the spheres, the absolute value of the interaction energy decreases with increasing electrolyte ion concentration and increases with increasing temperature. At zero electrolyte ion concentration, the derived analytical equation transforms into the Coulomb Equation Finally, the analytical equation is generalized to calculate the electric interaction energy of N separated, charged spheres surrounded by electrolyte.

Advancement and Challenges of Biosensing Using Field Effect Transistors.

Field-effect transistors (FETs) have become eminent electronic devices for biosensing applications owing to their high sensitivity, faster response and availability of advanced fabrication techniques for their production. The device physics of this sensor is now well understood due to the emergence of several numerical modelling and simulation papers over the years. The pace of advancement along with the knowhow of theoretical concepts proved to be highly effective in detecting deadly pathogens, especially the SARS-CoV-2 spike protein of the coronavirus with the onset of the (coronavirus disease of 2019) COVID-19 pandemic. However, the advancement in the sensing system is also accompanied by various hurdles that degrade the performance. In this review, we have explored all these challenges and how these are tackled with innovative approaches, techniques and device modifications that have also raised the detection sensitivity and specificity. The functional materials of the device are also structurally modified towards improving the surface area and minimizing power dissipation for developing miniaturized microarrays applicable in ultra large scale integration (ULSI) technology. Several theoretical models and simulations have also been carried out in this domain which have given a deeper insight on the electron transport mechanism in these devices and provided the direction for optimizing performance.

Technical Perspectives on Applications of Biologically Coupled Gate Field-Effect Transistors.

Biosensing technologies are required for point-of-care testing (POCT). We determine some physical parameters such as molecular charge and mass, redox potential, and reflective index for measuring biological phenomena. Among such technologies, biologically coupled gate field-effect transistor (Bio-FET) sensors are a promising candidate as a type of potentiometric biosensor for the POCT because they enable the direct detection of ionic and biomolecular charges in a miniaturized device. However, we need to reconsider some technical issues of Bio-FET sensors to expand their possible use for biosensing in the future. In this perspective, the technical issues of Bio-FET sensors are pointed out, focusing on the shielding effect, pH signals, and unique parameters of FETs for biosensing. Moreover, other attractive features of Bio-FET sensors are described in this perspective, such as the integration and the semiconductive materials used for the Bio-FET sensors.

Electronic to ionic transduction of the electric field applied to PEDOT:PSS substrates to the cell cultures on top.

The potential of the electrical double layer (EDL) formed at the interface between cross-linked poly (3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) and phosphate-buffered saline (PBS) was measured with respect to a reference Ag/AgCl electrode, yielding a value of ca. 300 mV, which corresponds to a work function of 4.9 eV. More importantly, we report that the application of a voltage along the PEDOT:PSS substrate induces a modification of the EDL, which mirrors the potential applied to the PEDOT:PSS underneath. This is translated into an ionic electric field, tangential to the interface that images the electric field applied to the PEDOT:PSS. We propose that this modification of the EDL, via application of the electrical field away from the cell culture medium, is at origin of the neural stem cell response to that field, when cultured on top of PEDOT:PSS. Despite the comparatively low value of the Debye length (estimated around 1 nm) with respect to the much larger cell to PEDOT:PSS surface distance, we believe that the perturbation of the EDL is the likely source of the increase of neuronal differentiation of the neural stem cells. We discuss other possible implications of that EDL modulation.

Ten Years Progress of Electrical Detection of Heavy Metal Ions (HMIs) Using Various Field-Effect Transistor (FET) Nanosensors: A Review.

Heavy metal pollution remains a major concern for the public today, in line with the growing population and global industrialization. Heavy metal ion (HMI) is a threat to human and environmental safety, even at low concentrations, thus rapid and continuous HMI monitoring is essential. Among the sensors available for HMI detection, the field-effect transistor (FET) sensor demonstrates promising potential for fast and real-time detection. The aim of this review is to provide a condensed overview of the contribution of certain semiconductor substrates in the development of chemical and biosensor FETs for HMI detection in the past decade. A brief introduction of the FET sensor along with its construction and configuration is presented in the first part of this review. Subsequently, the FET sensor deployment issue and FET intrinsic limitation screening effect are also discussed, and the solutions to overcome these shortcomings are summarized. Later, we summarize the strategies for HMIs' electrical detection, mechanisms, and sensing performance on nanomaterial semiconductor FET transducers, including silicon, carbon nanotubes, graphene, AlGaN/GaN, transition metal dichalcogenides (TMD), black phosphorus, organic and inorganic semiconductor. Finally, concerns and suggestions regarding detection in the real samples using FET sensors are highlighted in the conclusion.

Enhancing the Hydrogen-Sensing Performance of p-Type PdO by Modulating the Conduction Model.

The implementation of the p-type metal oxide semiconductor (MOS) in modern sensing systems requires a strategy to effectively enhance its inherent low response. However, for p-type MOS sensors, conventional methods such as catalyst nanoparticle (NP) decoration and grain size regulation do not work as effectively as they do for n-type MOS sensors, which is basically due to the fact that the p-type MOS adopts an unfavorable parallel conduction model. Herein, taking Au@PdO as an example, we demonstrate that the conduction model of the p-type MOS can be manipulated into the series conduction model by inserting a high-conductive metallic core into less-conductive p-type MOS NPs. This unique series conduction model makes the sensor response of Au@PdO nanoparticle arrays (NAs) very sensitive to the catalyst NP decoration as well as the change of structural parameters. For example, Au@PdO NAs demonstrate an ∼9000 times increase in sensor response when decorated with Pd NPs, whereas there is only ∼100 times increase for PdO NAs. This greatly improved response value outperforms all previously reported PdO-based (and most other p-type semiconductor-based) H2 sensors, which helps the obtained sensor to achieve an ultralow detection limit of ∼0.1 ppm at room temperature. Additionally, Au@PdO NAs inherit the high surface reactivity and gas adsorption property of p-type PdO. As a result, the as-prepared sensor exhibits high humidity-resistive property and excellent selectivity. This work provides a new strategy to significantly enhance the sensing performance of p-type gas sensors by manipulating their conduction model.

Influence of the Electrolyte Salt Concentration on DNA Detection with Graphene Transistors.

Liquid-gated Graphene Field-Effect Transistors (GFET) are ultrasensitive bio-detection platforms carrying out the graphene's exceptional intrinsic functionalities. Buffer and dilution factor are prevalent strategies towards the optimum performance of the GFETs. However, beyond the Debye length (λD), the role of the graphene-electrolytes' ionic species interactions on the DNA behavior at the nanoscale interface is complicated. We studied the characteristics of the GFETs under different ionic strength, pH, and electrolyte type, e.g., phosphate buffer (PB), and phosphate buffer saline (PBS), in an automatic portable built-in system. The electrostatic gating and charge transfer phenomena were inferred from the field-effect measurements of the Dirac point position in single-layer graphene (SLG) transistors transfer curves. Results denote that λD is not the main factor governing the effective nanoscale screening environment. We observed that the longer λD was not the determining characteristic for sensitivity increment and limit of detection (LoD) as demonstrated by different types and ionic strengths of measuring buffers. In the DNA hybridization study, our findings show the role of the additional salts present in PBS, as compared to PB, in increasing graphene electron mobility, electrostatic shielding, intermolecular forces and DNA adsorption kinetics leading to an improved sensitivity.

Divalent Cation Dependence Enhances Dopamine Aptamer Biosensing.

Oligonucleotide receptors (aptamers), which change conformation upon target recognition, enable electronic biosensing under high ionic-strength conditions when coupled to field-effect transistors (FETs). Because highly negatively charged aptamer backbones are influenced by ion content and concentration, biosensor performance and target sensitivities were evaluated under application conditions. For a recently identified dopamine aptamer, physiological concentrations of Mg2+ and Ca2+ in artificial cerebrospinal fluid produced marked potentiation of dopamine FET-sensor responses. By comparison, divalent cation-associated signal amplification was not observed for FET sensors functionalized with a recently identified serotonin aptamer or a previously reported dopamine aptamer. Circular dichroism spectroscopy revealed Mg2+- and Ca2+-induced changes in target-associated secondary structure for the new dopamine aptamer, but not the serotonin aptamer nor the old dopamine aptamer. Thioflavin T displacement corroborated the Mg2+ dependence of the new dopamine aptamer for target detection. These findings imply allosteric binding interactions between divalent cations and dopamine for the new dopamine aptamer. Developing and testing sensors in ionic environments that reflect intended applications are best practices for identifying aptamer candidates with favorable attributes and elucidating sensing mechanisms.

Accurate Determination of the Quantity and Spatial Distribution of Counterions around a Spherical Macroion.

The accurate distribution of countercations (Rb+ and Sr2+ ) around a rigid, spherical, 2.9-nm size polyoxometalate cluster, {Mo132 }42- , is determined by anomalous small-angle X-ray scattering. Both Rb+ and Sr2+ ions lead to shorter diffuse lengths for {Mo132 } than prediction. Most Rb+ ions are closely associated with {Mo132 } by staying near the skeleton of {Mo132 } or in the Stern layer, whereas more Sr2+ ions loosely associate with {Mo132 } in the diffuse layer. The stronger affinity of Rb+ ions towards {Mo132 } than that of Sr2+ ions explains the anomalous lower critical coagulation concentration of {Mo132 } with Rb+ compared to Sr2+ . The anomalous behavior of {Mo132 } can be attributed to majority of negative charges being located at the inner surface of its cavity. The longer anion-cation distance weakens the Coulomb interaction, making the enthalpy change owing to the breakage of hydration layers of cations more important in regulating the counterion-{Mo132 } interaction.

Re-entrant swelling and redissolution of polyelectrolytes arises from an increased electrostatic decay length at high salt concentrations.

HYPOTHESIS: A detailed understanding of the influence of electrolytes on the conformation of polyelectrolyte chains is an important goal made challenging by the strong coupling between electrostatic interactions and chain conformation. This challenge is particularly evident at moderate to high salt concentrations where mean-field theories of electrolytes are no longer applicable and are therefore unable to predict the interactions between neutral or like charged surfaces that leads to re-entrant swelling of DNA and other polyelectrolytes at high salt concentrations. Recent developments arising from studies of surface forces in ionic liquids that have been extended to include a wide variety of monovalent electrolytes reveal a hitherto unknown increase in the electrostatic decay length at high electrolyte concentrations. We hypothesise that the re-entrant behaviour of polyelectrolytes is driven by an increasing electrostatic decay length with increasing electrolyte concentration. EXPERIMENTS: We survey numerous experiments in the literature on re-entrant swelling and calculate the effect of ion pairing on the electrostatic decay length in concentrated electrolytes. FINDINGS: Re-entrant solubility is driven by an increasing electrostatic decay length at high salt concentrations and is universal across all polyelectrolytes.