Toward robust quantification of dopamine and serotonin in mixtures using nano-graphitic carbon sensors.

Monitoring the coordinated signaling of dopamine (DA) and serotonin (5-HT) is important for advancing our understanding of the brain. However, the co-detection and robust quantification of these signals at low concentrations is yet to be demonstrated. Here, we present the quantification of DA and 5-HT using nano-graphitic (NG) sensors together with fast-scan cyclic voltammetry (FSCV) employing an engineered N-shape potential waveform. Our method yields 6% error in quantifying DA and 5-HT analytes present in in vitro mixtures at concentrations below 100 nM. This advance is due to the electrochemical properties of NG sensors which, in combination with the engineered FSCV waveform, provided distinguishable cyclic voltammograms (CVs) for DA and 5-HT. We also demonstrate the generalizability of the prediction model across different NG sensors, which arises from the consistent voltammetric fingerprints produced by our NG sensors. Curiously, the proposed engineered waveform also improves the distinguishability of DA and 5-HT CVs obtained from traditional carbon fiber (CF) microelectrodes. Nevertheless, this improved distinguishability of CVs obtained from CF is inferior to that of NG sensors, arising from differences in the electrochemical properties of the sensor materials. Our findings demonstrate the potential of NG sensors and our proposed FSCV waveform for future brain studies.

Unraveling the complex electrochemistry of serotonin using engineered graphitic sensors.

Fast-scan cyclic voltammetry (FSCV) with micron-sized carbon sensors is a promising approach for monitoring the fast dynamics of serotonin (5-HT) neuromodulatory signals in the brain. However, sensor performance using FSCV can be compromised by complex chemical reactions associated with the reduction and oxidation of 5-HT, posing considerable challenges to detection of 5-HT in vivo. Herein we describe the use of engineered graphitic sensors to characterize the complex electrochemistry of 5-HT under a wide range of measurement conditions, with the aim of optimizing the FSCV conditions for in vivo quantitative 5-HT detection. These measurements reveal that water plays a significant role in driving side reactions during low-voltage FSCV measurements, leading to the observation of a well-defined secondary redox couple we associated with the redox reaction of tryptamine 4,5-dione. Remarkably, these side reactions can persist subsequent to the primary redox events associated with 5-HT. Furthermore, the results reveal a critical deviation from this ideal redox behavior if the FSCV anodic limit exceeds +0.8 V, which can be attributed to the generation of radical species from water oxidation. These new insights could lead to new FSCV protocols for more reliable 5-HT detection.

Mechanisms of Interface Cleaning in Heterostructures Made from Polymer-Contaminated Graphene.

Heterostructures obtained from layered assembly of 2D materials such as graphene and hexagonal boron nitride have potential in the development of new electronic devices. Whereas various materials techniques can now produce macroscopic scale graphene, the construction of similar size heterostructures with atomically clean interfaces is still unrealized. A primary barrier has been the inability to remove polymeric residues from the interfaces that arise between layers when fabricating heterostructures. Here, the interface cleaning problem of polymer-contaminated heterostructures is experimentally studied from an energy viewpoint. With this approach, it is established that the interface cleaning mechanism involves a combination of thermally activated polymer residue mobilization and their mechanical actuation. This framework allows a systematic approach for fabricating record large-area clean heterostructures from polymer-contaminated graphene. These heterostructures provide state-of-the-art electronic performance. This study opens new strategies for the scalable production of layered materials heterostructures.

Assessing the aneurysm occlusion efficacy of a shear-thinning biomaterial in a 3D-printed model.

Metallic coil embolization is a common method for the endovascular treatment of visceral artery aneurysms (VAA) and visceral artery pseudoaneurysms (VAPA); however, this treatment is suboptimal due to the high cost of coils, incomplete volume occlusion, poor reendothelialization, aneurysm puncture, and coil migration. Several alternative treatment strategies are available, including stent flow diverters, glue embolics, gelfoam slurries, and vascular mesh plugs-each of which have their own disadvantages. Here, we investigated the in vitro capability of a shear-thinning biomaterial (STB), a nanocomposite hydrogel composed of gelatin and silicate nanoplatelets, for the minimally-invasive occlusion of simple necked aneurysm models. We demonstrated the injectability of STB through various clinical catheters, engineered an in vitro testing apparatus to independently manipulate aneurysm neck diameter, fluid flow rate, and flow waveform, and tested the stability of STB within the models under various conditions. Our experiments show that STB is able to withstand at least 1.89 Pa of wall shear stress, as estimated by computational fluid dynamics. STB is also able to withstand up to 10 mL s-1 pulsatile flow with a waveform mimicking blood flow in the human femoral artery and tolerate greater pressure changes than those in the human aorta. We ultimately found that our in vitro system was limited by supraphysiologic pressure changes caused by aneurysm models with low compliance.

Anomalous sensitivity enhancement of nano-graphitic electrochemical micro-sensors with reducing the operating voltage.

Microscopic interactions between electrochemical sensors and biomolecules critically influence the sensitivity. Here, we report an unexpected dependence of the sensitivity on the upper potential limit (UPL) in voltammetry experiments. In particular, we find that the sensitivity of substrate-supported nano-graphitic micro-sensors in response to dopamine increases almost linearly with the inverse of UPL in voltammetry experiments with rapid potential sweeps. Our experiments and multi-physics simulations reveal that the main cause behind this phenomenon is the UPL-induced electrostatic force that influences the steady-state number of dopamine molecules on the sensor surface. Our findings illustrate a new strategy for enhancing the performance of planar electrochemical micro-sensors.

An Electrochemical Biochip for Measuring Low Concentrations of Analytes With Adjustable Temporal Resolutions.

Electrochemical micro-sensors made of nano-graphitic (NG) carbon materials could offer high sensitivity and support voltammetry measurements at vastly different temporal resolutions. Here, we implement a configurable CMOS biochip for measuring low concentrations of bio-analytes by leveraging these advantageous features of NG micro-sensors. In particular, the core of the biochip is a discrete-time ∆Σ modulator, which can be configured for optimal power consumption according to the temporal resolution requirements of the sensing experiments while providing a required precision of ≈ 13 effective number of bits. We achieve this new functionality by developing a design methodology using the physical models of transistors, which allows the operating region of the modulator to be switched on-demand between weak and strong inversion. We show the application of this configurable biochip through in-vitro measurements of dopamine with concentrations as low as 50 nM and 200 nM at temporal resolutions of 100 ms and 10 s, respectively.

Nano-engineering the material structure of preferentially oriented nano-graphitic carbon for making high-performance electrochemical micro-sensors.

Direct synthesis of thin-film carbon nanomaterials on oxide-coated silicon substrates provides a viable pathway for building a dense array of miniaturized (micron-scale) electrochemical sensors with high performance. However, material synthesis generally involves many parameters, making material engineering based on trial and error highly inefficient. Here, we report a two-pronged strategy for producing engineered thin-film carbon nanomaterials that have a nano-graphitic structure. First, we introduce a variant of the metal-induced graphitization technique that generates micron-scale islands of nano-graphitic carbon materials directly on oxide-coated silicon substrates. A novel feature of our material synthesis is that, through substrate engineering, the orientation of graphitic planes within the film aligns preferentially with the silicon substrate. This feature allows us to use the Raman spectroscopy for quantifying structural properties of the sensor surface, where the electrochemical processes occur. Second, we find phenomenological models for predicting the amplitudes of the redox current and the sensor capacitance from the material structure, quantified by Raman. Our results indicate that the key to achieving high-performance micro-sensors from nano-graphitic carbon is to increase both the density of point defects and the size of the graphitic crystallites. Our study offers a viable strategy for building planar electrochemical micro-sensors with high-performance.

Versatile construction of van der Waals heterostructures using a dual-function polymeric film.

The proliferation of van der Waals (vdW) heterostructures formed by stacking layered materials can accelerate scientific and technological advances. Here, we report a strategy for constructing vdW heterostructures through the interface engineering of the exfoliation substrate using a sub-5 nm polymeric film. Our construction method has two main features that distinguish it from existing techniques. First is the consistency of its exfoliation process in increasing the yield and in producing large (>10,000 µm2) monolayer graphene. Second is the applicability of its layer transfer process to different layered materials without requiring a specialized stamp-a feature useful for generalizing the assembly process. We demonstrate vdW graphene devices with peak carrier mobility of 200,000 and 800,000 cm2 V-1 s-1 at room temperature and 9 K, respectively. The simplicity of our construction method and its versatility to different layered materials may open doors for automating the fabrication process of vdW heterostructures.

Quantum Tunneling Mediated Interfacial Synthesis of a Benzofuran Derivative.

Reaction pathways involving quantum tunneling of protons are fundamental to chemistry and biology. They are responsible for essential aspects of interstellar synthesis, the degradation and isomerization of compounds, enzymatic activity, and protein dynamics. On-surface conditions have been demonstrated to open alternative routes for organic synthesis, often with intricate transformations not accessible in solution. Here, we investigate a hydroalkoxylation reaction of a molecular species adsorbed on a Ag(111) surface by scanning tunneling microscopy complemented by X-ray electron spectroscopy and density functional theory. The closure of the furan ring proceeds at low temperature (down to 150 K) and without detectable side reactions. We unravel a proton-tunneling-mediated pathway theoretically and confirm experimentally its dominant contribution through the kinetic isotope effect with the deuterated derivative.