Current methods for hyperpolarized [1-13C]pyruvate MRI human studies.

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of HP agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate-by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation; (2) MRI system setup and calibrations; (3) data acquisition and image reconstruction; and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the "HP 13C MRI Consensus Group" as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods and Equipment study groups. It further aims to provide a comprehensive reference for future consensus, building as the field continues to advance human studies with this metabolic imaging modality.

The organo-metal-like nature of long-range conduction in cable bacteria.

Cable bacteria are filamentous, multicellular microorganisms that display an exceptional form of biological electron transport across centimeter-scale distances. Currents are guided through a network of nickel-containing protein fibers within the cell envelope. Still, the mechanism of long-range conduction remains unresolved. Here, we characterize the conductance of the fiber network under dry and wet, physiologically relevant, conditions. Our data reveal that the fiber conductivity is high (median value: 27 S cm-1; range: 2 to 564 S cm-1), does not show any redox signature, has a low thermal activation energy (Ea = 69 ± 23 meV), and is not affected by humidity or the presence of ions. These features set the nickel-based conduction mechanism in cable bacteria apart from other known forms of biological electron transport. As such, conduction resembles that of an organic semi-metal with a high charge carrier density. Our observation that biochemistry can synthesize an organo-metal-like structure opens the way for novel bio-based electronic technologies.

Simultaneous Measurement of GABA, Glutathione, and Glutamate-Glutamine in the Thalamus using Edited MR Spectroscopy: Feasibility and Applications in Traumatic Brain Injury.

BACKGROUND: MR spectroscopy (MRS) is a noninvasive tool for evaluating biochemical alterations, such as glutamate (Glu)/gamma-aminobutyric acid (GABA) imbalance and depletion of antioxidative glutathione (GSH) after traumatic brain injury (TBI). Thalamus, a critical and vulnerable region post-TBI, is challenging for MRS acquisitions, necessitating optimization to simultaneously measure GABA/Glu and GSH. PURPOSE: To assess the feasibility and optimize acquisition and processing approaches for simultaneously measuring GABA, Glx (Glu + glutamine (Gln)), and GSH in the thalamus, employing Hadamard encoding and reconstruction of MEscher-GArwood (MEGA)-edited spectroscopy (HERMES). STUDY TYPE: Prospective. SUBJECTS: 28 control subjects (age: 35.9 ± 15.1 years), and 17 mild TBI (mTBI) patients (age: 32.4 ± 11.3 years). FIELD STRENGTH/SEQUENCE: 3T/T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE), HERMES. ASSESSMENT: We evaluated the impact of acquisition with spatial saturation bands and post-processing with spectral alignment on HERMES performance in the thalamus among controls. Within-subject variability was examined in five controls through repeated scans within a week. The HERMES spectra in the posterior cingulate cortex (PCC) of controls were used as a reference for assessing HERMES performance in a reliable target. Furthermore, we compared metabolite levels and fitting quality in the thalamus between mTBI patients and controls. STATISTICAL TESTS: Unpaired t-tests and within-subject coefficient-of-variation (CV). A P-value <0.05 was deemed significant. RESULTS: HERMES spectra, acquired with saturation bands and processed with spectral alignment, yielded reliable metabolite measurements in the thalamus. The mean within-subject CV for GABA, Glx, and GSH levels were 18%, 10%, and 16% in the thalamus (7%, 9%, and 16% in the PCC). GABA (3.20 ± 0.60 vs 2.51 ± 0.55, P < 0.01) and Glx (8.69 ± 1.23 vs 7.72 ± 1.19, P = 0.03) levels in the thalamus were significantly higher in mTBI patients than in controls, with GSH (1.27 ± 0.35 vs 1.22 ± 0.28, P = 0.65) levels showing no significant difference. DATA CONCLUSION: Simultaneous measuring GABA/Glx and GSH using HERMES is feasible in the thalamus, providing valuable insight into TBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Investigating the origin of the 13 C lactate signal in the anesthetized healthy rat brain in vivo after hyperpolarized [1-13 C]pyruvate injection.

The goal of this study was to investigate the origin of brain lactate (Lac) signal in the healthy anesthetized rat after injection of hyperpolarized (HP) [1-13 C]pyruvate (Pyr). Dynamic two-dimensional spiral chemical shift imaging with flow-sensitizing gradients revealed reduction in both vascular and brain Pyr, while no significant dependence on the level of flow suppression was detected for Lac. These results support the hypothesis that the HP metabolites predominantly reside in different compartments in the brain (i.e., Pyr in the blood and Lac in the parenchyma). Data from high-resolution metabolic imaging of [1-13 C]Pyr further demonstrated that Lac detected in the brain was not from contributions of vascular signal attributable to partial volume effects. Additionally, metabolite distributions and kinetics measured with dynamic imaging after injection of HP [1-13 C]Lac were similar to Pyr data when Pyr was used as the substrate. These data do not support the hypothesis that Lac observed in the brain after Pyr injection was generated in other organs and then transported across the blood-brain barrier (BBB). Together, the presented results provide further evidence that even in healthy anesthetized rats, the transport of HP Pyr across the BBB is sufficiently fast to permit detection of its metabolic conversion to Lac within the brain.

Highly sensitive detection of malaria biomarker through matching channel and gate capacitance of integrated organic electrochemical transistors.

Organic electrochemical transistors (OECTs) possess versatile advantages for biochemical and electrophysiological applications due to electrochemical gating and ion-to-electron conversion capability. Although OECTs have been successfully applied for biochemical sensing, the effect of relative capacitance for specific sensing events is still unclear. In the present work, we design integrated interdigitated OECTs (iOECTs) with on-plane gold gate and different channel geometries for point-of-care diagnosis of malaria using aptamer as receptor. The transconductance of the iOECTs gated with micro-size gold electrodes decreased with increasing the channel thicknesses, especially for devices with large channel areas, which is inconsistent with devices gated by typical Ag/AgCl electrodes, attributing to the limited gating efficiency of the micro-size gate electrode. The capacitance of gate electrode was heavily suppressed by receptors but increased with the incubation of targets. In addition, the integrated iOECTs with thin channels exhibited superior sensitivity for malaria detection with the detection limit as low as 3.2 aM, much lower than their thick channel counterpart and other state-of-the-art biosensors. These deviations could be caused by the high relative capacitances, with respect to the gate and channel capacitance (Cg/Cch), resulting in a high gate potential drop over the organic channel and thus entirely gating on the thin channel device. These findings provide guidance to optimize the geometry of OECT devices with on-chip integrated gates and the fabrication of miniaturized OECTs for biosensing applications.

Truncated Electrochemical Aptasensor with Enhanced Antifouling Capability for Highly Sensitive Serotonin Detection.

Accurate determination of serotonin (ST) provides insight into neurological processes and enables applications in clinical diagnostics of brain diseases. Herein, we present an electrochemical aptasensor based on truncated DNA aptamers and a polyethylene glycol (PEG) molecule-functionalized sensing interface for highly sensitive and selective ST detection. The truncated aptamers have a small size and adopt a stable stem-loop configuration, which improves the accessibility of the aptamer for the analyte and enhances the sensitivity of the aptasensor. Upon target binding, these aptamers perform a conformational change, leading to a variation in the Faraday current of the redox tag, which was recorded by square wave voltammetry (SWV). Using PEG as blocking molecules minimizes nonspecific adsorption of other interfering molecules and thus endows an enhanced antifouling ability. The proposed electrochemical aptamer sensor showed a wide range of detection lasting from 0.1 nM to 1000 nM with a low limit of detection of 0.14 nM. Owing to the unique properties of aptamer receptors, the aptasensor also exhibits high selectivity and stability. Furthermore, with the reduced unspecific adsorption, assaying of ST in human serum and artificial cerebrospinal fluid (aCSF) showed excellent performance. The reported strategy of utilizing antifouling PEG describes a novel approach to building antifouling aptasensors and holds great potential for neurochemical investigations and clinical diagnosis.

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies.

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation, (2) MRI system setup and calibrations, (3) data acquisition and image reconstruction, and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the "HP 13C MRI Consensus Group" as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods & Equipment study groups. It further aims to provide a comprehensive reference for future consensus building as the field continues to advance human studies with this metabolic imaging modality.

A Combined Plasmonic and Electrochemical Aptasensor Based on Gold Nanopit Arrays for the Detection of Human Serum Albumin.

Electrochemical and optical platforms are commonly employed in designing biosensors. However, one signal readout can easily lead to inaccuracies due to the effect of nonstandard test procedures, different operators, and experimental environments. We have developed a dual-signal protocol that combined two transducer principles in one aptamer-based biosensor by simultaneously performing electrochemical- and extraordinary optical transmission (EOT)-based plasmonic detection using gold nanopit arrays (AuNpA). Compared with full hole structures, we found that nanopits, that did not fully penetrate the gold film, not only exhibited a better plasmonic bandwidth and refractive index sensitivity both in the finite-difference time-domain simulation and in experiments by shielding the gold/quartz mode but also enlarged the electrochemical active surface area. Therefore, the periodic non-fully penetrating AuNpA were modified with ferrocene-labeled human serum albumin aptamer receptors. The formation of the receptor layer and human serum albumin binding complex induced a conformational change, which resulted in variation in the electron transfer between the electro-active ferrocene units and the AuNpA surface. Simultaneously, the binding event caused a surface plasmon polaritons wavelength shift corresponding to a change in the surface refractive index. Interestingly, although both transducers recorded the same binding process, they led to different limits of detection, dynamic ranges, and sensitivities. The electrochemical transducer showed a dynamic detection range from 1 nM to 600 µM, while the optical transducer covered high concentrations from 100 µM to 600 µM. This study not only provides new insights into the design of plasmonic nanostructures but also potentially opens an exciting avenue for dual-signal disease diagnosis and point-of-care testing applications.

Validation of transparent and flexible neural implants for simultaneous electrophysiology, functional imaging, and optogenetics.

The combination of electrophysiology and neuroimaging methods allows the simultaneous measurement of electrical activity signals with calcium dynamics from single neurons to neuronal networks across distinct brain regions in vivo. While traditional electrophysiological techniques are limited by photo-induced artefacts and optical occlusion for neuroimaging, different types of transparent neural implants have been proposed to resolve these issues. However, reproducing proposed solutions is often challenging and it remains unclear which approach offers the best properties for long-term chronic multimodal recordings. We therefore created a streamlined fabrication process to produce, and directly compare, two types of transparent surface micro-electrocorticography (µECoG) implants: nano-mesh gold structures (m-µECoGs) versus a combination of solid gold interconnects and PEDOT:PSS-based electrodes (pp-µECoGs). Both implants allowed simultaneous multimodal recordings but pp-µECoGs offered the best overall electrical, electrochemical, and optical properties with negligible photo-induced artefacts to light wavelengths of interest. Showing functional chronic stability for up to four months, pp-µECoGs also allowed the simultaneous functional mapping of electrical and calcium neural signals upon visual and tactile stimuli during widefield imaging. Moreover, recordings during two-photon imaging showed no visible signal attenuation and enabled the correlation of network dynamics across brain regions to individual neurons located directly below the transparent electrical contacts.

Determination of Stiffness and the Elastic Modulus of 3D-Printed Micropillars with Atomic Force Microscopy-Force Spectroscopy.

Nowadays, many applications in diverse fields are taking advantage of micropillars such as optics, tribology, biology, and biomedical engineering. Among them, one of the most attractive is three-dimensional microelectrode arrays for in vivo and in vitro studies, such as cellular recording, biosensors, and drug delivery. Depending on the application, the micropillar's optimal mechanical response ranges from soft to stiff. For long-term implantable devices, a mechanical mismatch between the micropillars and the biological tissue must be avoided. For drug delivery patches, micropillars must penetrate the skin without breaking or bending. The accurate mechanical characterization of the micropillar is pivotal in the fabrication and optimization of such devices, as it determines whether the device will fail or not. In this work, we demonstrate an experimental method based only on atomic force microscopy-force spectroscopy that allows us to measure the stiffness of a micropillar and the elastic modulus of its constituent material. We test our method with four different types of 3D inkjet-printed micropillars: silver micropillars sintered at 100 and 150 °C and polyacrylate microstructures with and without a metallic coating. The estimated elastic moduli are found to be comparable with the corresponding bulk values. Furthermore, our findings show that neither the sintering temperature nor the presence of a thin metal coating plays a major role in defining the mechanical properties of the micropillar.

On-Chip Electrokinetic Micropumping for Nanoparticle Impact Electrochemistry.

Single-entity electrochemistry is a powerful technique to study the interactions of nanoparticles at the liquid-solid interface. In this work, we exploit Faradaic (background) processes in electrolytes of moderate ionic strength to evoke electrokinetic transport and study its influence on nanoparticle impacts. We implemented an electrode array comprising a macroscopic electrode that surrounds a set of 62 spatially distributed microelectrodes. This configuration allowed us to alter the global electrokinetic transport characteristics by adjusting the potential at the macroscopic electrode, while we concomitantly recorded silver nanoparticle impacts at the microscopic detection electrodes. By focusing on temporal changes of the impact rates, we were able to reveal alterations in the macroscopic particle transport. Our findings indicate a potential-dependent micropumping effect. The highest impact rates were obtained for strongly negative macroelectrode potentials and alkaline solutions, albeit also positive potentials lead to an increase in particle impacts. We explain this finding by reversal of the pumping direction. Variations in the electrolyte composition were shown to play a critical role as the macroelectrode processes can lead to depletion of ions, which influences both the particle oxidation and the reactions that drive the transport. Our study highlights that controlled on-chip micropumping is possible, yet its optimization is not straightforward. Nevertheless, the utilization of electro- and diffusiokinetic transport phenomena might be an appealing strategy to enhance the performance in future impact-based sensing applications.

Prototype Digital Lateral Flow Sensor Using Impact Electrochemistry in a Competitive Binding Assay.

This work demonstrates a lateral flow assay concept on the basis of stochastic-impact electrochemistry. To this end, we first elucidate requirements to employ silver nanoparticles as redox-active labels. Then, we present a prototype that utilizes nanoimpacts from biotinylated silver nanoparticles as readouts to detect free biotin in solution based on competitive binding. The detection is performed in a membrane-based microfluidic system, where free biotin and biotinylated particles compete for streptavidin immobilized on embedded latex beads. Excess nanoparticles are then registered downstream at an array of detection electrodes. In this way, we establish a proof of concept that serves as a blueprint for future "digital" lateral flow sensors.

Delineating charge and capacitance transduction in system-integrated graphene-based BioFETs used as aptasensors for malaria detection.

Despite significant eradication efforts, malaria remains a persistent infectious disease with high mortality due to the lack of efficient point-of-care (PoC) screening solutions required to manage low-density asymptomatic parasitemia. In response, we demonstrate a quantitative electrical biosensor based on system-integrated two-dimensional field-effect transistors (2DBioFETs) of reduced graphene oxide (rGO) as transducer for high sensitivity screening of the main malaria biomarker, Plasmodium falciparum lactate dehydrogenase (PfLDH). The 2DBioFETs were biofunctionalized with pyrene-modified 2008s aptamers as specific PfLDH receptors. While we systematically optimize biosensor interface for optimal performance, aptamer-protein transduction at 2DBioFETs is elucidated based on delineation of charge and capacitance in an updated analytical model for two-dimensional rGO/biofunctional layer/electrolyte (2DiBLE) interfaces. Our 2DBioFET-aptasensors display a limit-of-detection down to 0.78 fM (0.11 pg/mL), dynamic ranges over 9 orders of magnitude (subfemto to submicromolar), high sensitivity, and selectivity in human serum validating their diagnostic potential as rapid PoC tests for malarial management.

DNA aptamer selection for SARS-CoV-2 spike glycoprotein detection.

The rapid spread of SARS-CoV-2 infection throughout the world led to a global public health and economic crisis triggering an urgent need for the development of low-cost vaccines, therapies and high-throughput detection assays. In this work, we used a combination of Ideal-Filter Capillary Electrophoresis SELEX (IFCE-SELEX), Next Generation Sequencing (NGS) and binding assays to isolate and validate single-stranded DNA aptamers that can specifically recognize the SARS-CoV-2 Spike glycoprotein. Two selected non-competing DNA aptamers, C7 and C9 were successfully used as sensitive and specific biological recognition elements for the development of electrochemical and fluorescent aptasensors for the SARS-CoV-2 Spike glycoprotein with detection limits of 0.07 fM and 41.87 nM, respectively.

Gold nanostructures: synthesis, properties, and neurological applications.

Recent advances in technology are expected to increase our current understanding of neuroscience. Nanotechnology and nanomaterials can alter and control neural functionality in both in vitro and in vivo experimental setups. The intersection between neuroscience and nanoscience may generate long-term neural interfaces adapted at the molecular level. Owing to their intrinsic physicochemical characteristics, gold nanostructures (GNSs) have received much attention in neuroscience, especially for combined diagnostic and therapeutic (theragnostic) purposes. GNSs have been successfully employed to stimulate and monitor neurophysiological signals. Hence, GNSs could provide a promising solution for the regeneration and recovery of neural tissue, novel neuroprotective strategies, and integrated implantable materials. This review covers the broad range of neurological applications of GNS-based materials to improve clinical diagnosis and therapy. Sub-topics include neurotoxicity, targeted delivery of therapeutics to the central nervous system (CNS), neurochemical sensing, neuromodulation, neuroimaging, neurotherapy, tissue engineering, and neural regeneration. It focuses on core concepts of GNSs in neurology, to circumvent the limitations and significant obstacles of innovative approaches in neurobiology and neurochemistry, including theragnostics. We will discuss recent advances in the use of GNSs to overcome current bottlenecks and tackle technical and conceptual challenges.

Single-Impact Electrochemistry in Paper-Based Microfluidics.

Microfluidic paper-based analytical devices (µPADs) have experienced an unprecedented story of success. In particular, as of today, most people have likely come into contact with one of their two most famous examples─the pregnancy or the SARS-CoV-2 antigen test. However, their sensing performance is constrained by the optical readout of nanoparticle agglomeration, which typically allows only qualitative measurements. In contrast, single-impact electrochemistry offers the possibility to quantify species concentrations beyond the pM range by resolving collisions of individual species on a microelectrode. Within this work, we investigate the integration of stochastic sensing into a µPAD design by combining a wax-patterned microchannel with a microelectrode array to detect silver nanoparticles (AgNPs) by their oxidative dissolution. In doing so, we demonstrate the possibility to resolve individual nanoparticle collisions in a reference-on-chip configuration. To simulate a lateral flow architecture, we flush previously dried AgNPs along a microchannel toward the electrode array, where we are able to record nanoparticle impacts. Consequently, single-impact electrochemistry poses a promising candidate to extend the limits of lateral flow-based sensors beyond current applications toward a fast and reliable detection of very dilute species on site.

Double-Resonant Nanostructured Gold Surface for Multiplexed Detection.

A novel double-resonant plasmonic substrate for fluorescence amplification in a chip-based apta-immunoassay is herein reported. The amplification mechanism relies on plasmon-enhanced fluorescence (PEF) effect. The substrate consists of an assembly of plasmon-coupled and plasmon-uncoupled gold nanoparticles (AuNPs) immobilized onto a glass slide. Plasmon-coupled AuNPs are hexagonally arranged along branch patterns whose resonance lies in the red band (∼675 nm). Plasmon-uncoupled AuNPs are sprinkled onto the substrate, and they exhibit a narrow resonance at 524 nm. Numerical simulations of the plasmonic response of the substrate through the finite-difference time-domain (FDTD) method reveal the presence of electromagnetic hot spots mainly confined in the interparticle junctions. In order to realize a PEF-based device for potential multiplexing applications, the plasmon resonances are coupled with the emission peak of 5-carboxyfluorescein (5-FAM) fluorophore and with the excitation/emission peaks of cyanine 5 (Cy5). The substrate is implemented in a malaria apta-immunoassay to detect Plasmodium falciparum lactate dehydrogenase (PfLDH) in human whole blood. Antibodies against Plasmodium biomarkers constitute the capture layer, whereas fluorescently labeled aptamers recognizing PfLDH are adopted as the top layer. The fluorescence emitted by 5-FAM and Cy5 fluorophores are linearly correlated (logarithm scale) to the PfLDH concentration over five decades. The limits of detection are 50 pM (1.6 ng/mL) with the 5-FAM probe and 260 fM (8.6 pg./mL) with the Cy5 probe. No sample preconcentration and complex pretreatments are required. Average fluorescence amplifications of 160 and 4500 are measured in the 5-FAM and Cy5 channel, respectively. These results are reasonably consistent with those worked out by FDTD simulations. The implementation of the proposed approach in multiwell-plate-based bioassays would lead to either signal redundancy (two dyes for a single analyte) or to a simultaneous detection of two analytes by different dyes, the latter being a key step toward high-throughput analysis.

Highly selective and sensitive detection of glutamate by an electrochemical aptasensor.

An electrochemical aptamer-based sensor was developed for glutamate, the major excitatory neurotransmitter in the central nervous system. Determining glutamic acid release and glutamic acid levels is crucial for studying signal transmission and for diagnosing pathological conditions in the brain. Glutamic acid-selective oligonucleotides were isolated from an ssDNA library using the Capture-SELEX protocol in complex medium. The selection permitted the isolation of an aptamer 1d04 with a dissociation constant of 12 µM. The aptamer sequence was further used in the development of an electrochemical aptamer sensor. For this purpose, a truncated aptamer sequence named glu1 was labelled with a ferrocene redox tag at the 3'-end and immobilized on a gold electrode surface via Au-thiol bonds. Using 6-mercapto-1-hexanol as the backfill, the sensor performance was characterized by alternating current voltammetry. The glu1 aptasensor showed a limit of detection of 0.0013 pM, a wide detection range between 0.01 pM and 1 nM, and good selectivity for glutamate in tenfold diluted human serum. With this enzyme-free aptasensor, the highly selective and sensitive detection of glutamate was demonstrated, which possesses great potential for implementation in microelectrodes and for in vitro as well as in vivo monitoring of neurotransmitter release.

Electrochemical Immunosensor Using Electroactive Carbon Nanohorns for Signal Amplification for the Rapid Detection of Carcinoembryonic Antigen.

In this work, a novel sandwich-type electrochemical immunosensor was developed for the quantitative detection of the carcinoembryonic antigen, an important tumor marker in clinical tests. The capture antibodies were immobilized on the surface of a gold disk electrode, while detection antibodies were attached to redox-tagged single-walled carbon nanohorns/thionine/AuNPs. Both types of antibody immobilization were carried out through Au-S bonds using the novel photochemical immobilization technique that ensures control over the orientation of the antibodies. The electroactive SWCNH/Thi/AuNPs nanocomposite worked as a signal tag to carry out both the detection of carcinoembryonic antigen and the amplification of the detection signal. The current response was monitored by differential pulse voltammetry. A clear dependence of the thionine redox peak was observed as a function of the carcinoembryonic antigen concentration. A linear detection range from 0.001-200 ng/mL and a low detection limit of 0.1385 pg/mL were obtained for this immunoassay. The results showed that carbon nanohorns represent a promising matrix for signal amplification in sandwich-type electrochemical immune assays working as a conductive and binding matrix with easy and versatile modification routes to antibody and redox tag immobilization, which possesses great potential for clinical diagnostics of CEA and other biomarkers.

The Structure of the Electric Double Layer of the Protic Ionic Liquid [Dema][TfO] Analyzed by Atomic Force Spectroscopy.

Protic ionic liquids are promising electrolytes for fuel cell applications. They would allow for an increase in operation temperatures to more than 100 °C, facilitating water and heat management and, thus, increasing overall efficiency. As ionic liquids consist of bulky charged molecules, the structure of the electric double layer significantly differs from that of aqueous electrolytes. In order to elucidate the nanoscale structure of the electrolyte-electrode interface, we employ atomic force spectroscopy, in conjunction with theoretical modeling using molecular dynamics. Investigations of the low-acidic protic ionic liquid diethylmethylammonium triflate, in contact with a platinum (100) single crystal, reveal a layered structure consisting of alternating anion and cation layers at the interface, as already described for aprotic ionic liquids. The structured double layer depends on the applied electrode potential and extends several nanometers into the liquid, whereby the stiffness decreases with increasing distance from the interface. The presence of water distorts the layering, which, in turn, significantly changes the system's electrochemical performance. Our results indicate that for low-acidic ionic liquids, a careful adjustment of the water content is needed in order to enhance the proton transport to and from the catalytic electrode.