Bottom-up designing nanostructured oxide libraries under a lab-on-chip paradigm towards a low-cost highly-selective E-nose

M. A. Solomatin; F. S. Fedorov; D. A. Kirilenko; V. Trouillet; A. S. Varezhnikov et al. 

Background: The multisensor concept has been developed as a powerful alternative to well-known gas-analytical instrumentation for applications where a fast but accurate and reliable assessment of the environment is required. The concept follows a biology-inspired approach where the selectivity towards various gases/odors is attained via pattern recognition of multisensory signal vectors. Herein, we discuss how to design a selective multisensor library based on various metal oxide nanostructures like a lab-on-chip using a simple but efficient bottom-up growth of materials over the multi-electrode chip under robust dc electrochemical protocols. Results: In addition to a conventional growth of oxide layers over the metal electrodes, we show that the fine nanowall-like oxide structures appear as a quasi-matrixed percolation film over the SiO2 substrate surface in the inter-electrode gaps to constitute a chemiresistive film. We have tested two directions while applying the technique to grow Co, Ni, Mn, and Zn oxides to develop on-chip sensor arrays of, (i) monoxide type employing the oxide films with gradual change of growth time, and (ii) multi-oxide type based on the four oxides. The materials were thoroughly characterized by electron microscopy, X-ray diffraction, thermogravimetric analysis, and X-ray photoelectron spectroscopy/mapping to prove the composition and structure. Among tested oxides, ZnO readily appears not only at the electric potential-targeted chip zone but also in other areas to dope the films for yielding heterojunctions with other oxides that enhances a variability of functional properties in the on-chip sensor array. The gas-sensing performance of the chips has been tested versus various chemically akin alcohol vapors at the sub- and low ppm range of concentrations in a mixture with air. Significance: We show that the grown oxide nanostructures exhibit a high-sensitive chemiresistive signal which allows one to build a multisensor vector signal, selective to the kind of alcohols, even at sub-ppm concentrations. Moreover, the multi-oxide library yields options for a superior selectivity under LDA metrics than the gradient-grown mono-oxide one due to the versatility of materials while the low-cost growth protocols remain to be the same in both cases. The delivered method to produce multisensor arrays allows one producing low-cost but efficient electronic nose units for numerous applications.

Controlled Sensing of User-Defined Aptamer-Based Targets Using Scanning Ionic Conductance Spectroscopy

H. Miljkovic; L. Feletti; G. Pistoletti Blanchet; M. Penedo; Z. Ayar et al. 

Solid-state nanopores offer the possibility of detecting disease biomarkers in early diagnostic applications. Standard approaches harness fingerprinting, where protein targets are bound to DNA carriers and detected in free translocation with a solid-state nanopore. However, they suffer from several drawbacks, including uncontrolled fast translocations, which lead to low detection accuracy and a low signal-to-noise ratio (SNR). This has hampered their application in clinical settings. Here, we propose a nanopore-based system capable of sensing selected molecules of interest from biological fluids by harnessing programmable aptamer sequences attached to DNA carrier systems that are tethered to glass surfaces. This allows for spatial and velocity control over translocation in the x, y, and z directions and enables the repeated scanning of the same analyte. The scanning ion conductance spectroscopy (SICS) based approach distinguishes itself from standard nanopore-based approaches with its ability to repeatedly scan the same aptamer molecule target site more than 5 times. We designed a DNA carrier with multiple binding sites for different aptamers to increase the yield of the experiment. Our approach achieves a detection rate of up to 74%, significantly higher than the 14% achieved with standard solid-state nanopore measurements. The strong spatial control also allows for significantly increased densities of aptamer target sites along the same DNA carrier, thereby paving the way for multiplexed sensing. The system offers user-defined programmability with different aptamer sequences, potentially expanding the use of our system to sense other disease biomarkers.

Intelligent and Self-Driving Microscopy of Protein Aggregation in Neurodegenerative Diseases

Monitoring Electrochemical Dynamics through Single-Molecule Imaging of hBN Surface Emitters in Organic Solvents

E. Mayner; N. Ronceray; M. Lihter; T-H. Chen; K. Watanabe et al. 

Electrochemical techniques conventionally lack spatial resolution and average local information over an entire electrode. While advancements in spatial resolution have been made through scanning probe methods, monitoring dynamics over large areas is still challenging, and it would be beneficial to be able to decouple the probe from the electrode itself. In this work, we leverage single molecule microscopy to spatiotemporally monitor analyte surface concentrations over a wide area using unmodified hexagonal boron nitride (hBN) in organic solvents. Through a sensing scheme based on redox-active species interactions with fluorescent emitters at the surface of hBN, we observe a region of a linear decrease in the number of emitters against increasingly positive potentials applied to a nearby electrode. We find consistent trends in electrode reaction kinetics vs overpotentials between potentiostat-reported currents and optically read emitter dynamics, showing Tafel slopes greater than 290 mV·decade-1. Finally, we draw on the capabilities of spectral single-molecule localization microscopy (SMLM) to monitor the fluorescent species’ identity, enabling multiplexed readout. Overall, we show dynamic measurements of analyte concentration gradients on a micrometer-length scale with nanometer-scale depth and precision. Considering the many scalable options for engineering fluorescent emitters with two-dimensional (2D) materials, our method holds promise for optically detecting a range of interacting species with exceptional localization precision.

Improvement of DERA activity and stability in the synthesis of statin precursors by immobilization on magnetic nanoparticles

D. Skendrović; A. Švarc; T. Rezić; A. Chernev; A. Radenovic et al. 

Higher stability and hyperactivation of the DERA enzyme were achieved by covalent bonding to magnetic nanoparticles with succinic anhydride as an activating agent.

CVD graphene contacts for lateral heterostructure MoS2 field effect transistors

D. S. Schneider; L. Lucchesi; E. Reato; Z. Wang; A. Piacentini et al. 

Intensive research has been carried out on two-dimensional materials, in particular molybdenum disulfide, towards high-performance field effect transistors for integrated circuits 1 . Fabricating transistors with ohmic contacts is a challenging task due to the formation of a high Schottky barrier that severely limits the performance of the transistors for real-world applications. Graphene-based heterostructures can be used in addition to, or as a substitute for unsuitable metals. In this paper, we present lateral heterostructure transistors made of scalable chemical vapor-deposited molybdenum disulfide and chemical vapor-deposited graphene achieving a low contact resistances of about 9 k Omegamu m and high on/off current ratios of 108. Furthermore, we also present a theoretical model calibrated on our experiments showing further potential for scaling transistors and contact areas into the few nanometers range and the possibility of a substantial performance enhancement by means of layer optimizations that would make transistors promising for use in future logic integrated circuits.

Nanofluidic logic with mechano-ionic memristive switches

T. Emmerich; Y. Teng; N. Ronceray; E. Lopriore; R. Chiesa et al. 

Neuromorphic systems are typically based on nanoscale electronic devices, but nature relies on ions for energy-efficient information processing. Nanofluidic memristive devices could thus potentially be used to construct electrolytic computers that mimic the brain down to its basic principles of operation. Here we report a nanofluidic device that is designed for circuit-scale in-memory processing. The device, which is fabricated using a scalable process, combines single-digit nanometric confinement and large entrance asymmetry and operates on the second timescale with a conductance ratio in the range of 9 to 60. In operando optical microscopy shows that the memory capabilities are due to the reversible formation of liquid blisters that modulate the conductance of the device. We use these mechano-ionic memristive switches to assemble logic circuits composed of two interactive devices and an ohmic resistor.

Label-Free Imaging of DNA Interactions with 2D Materials

J. Sülzle; W. Yang; Y. Shimoda; N. Ronceray; E. Mayner et al. 

Two-dimensional (2D) materials offer potential as substrates for biosensing devices, as their properties can be engineered to tune interactions between the surface and biomolecules. Yet, not many methods can measure these interactions in a liquid environment without introducing labeling agents such as fluorophores. In this work, we harness interferometric scattering (iSCAT) microscopy, a label-free imaging technique, to investigate the interactions of single molecules of long dsDNA with 2D materials. The millisecond temporal resolution of iSCAT allows us to capture the transient interactions and to observe the dynamics of unlabeled DNA binding to a hexagonal boron nitride (hBN) surface in solution for extended periods (including a fraction of 10%, of trajectories lasting longer than 110 ms). Using a focused ion beam technique to engineer defects, we find that DNA binding affinity is enhanced at defects; when exposed to long lanes, DNA binds preferentially at the lane edges. Overall, we demonstrate that iSCAT imaging is a useful tool to study how biomolecules interact with 2D materials, a key component in engineering future biosensors.

Open-source microscope add-on for structured illumination microscopy

M. T. M. Hannebelle; E. Raeth; S. M. Leitao; T. Lukes; J. Pospisil et al. 

Super-resolution techniques expand the abilities of researchers who have the knowledge and resources to either build or purchase a system. This excludes the part of the research community without these capabilities. Here we introduce the openSIM add-on to upgrade existing optical microscopes to Structured Illumination super-resolution Microscopes (SIM). The openSIM is an open-hardware system, designed and documented to be easily duplicated by other laboratories, making super-resolution modality accessible to facilitate innovative research. The add-on approach gives a performance improvement for pre-existing lab equipment without the need to build a completely new system.|Researchers developed an open-hardware structured illumination microscopy add-on. This affordable upgrade provides super-resolution capabilities for normal optical microscopes. Detailed instructions enable easy reproduction to help democratize advanced microscopy.

AI-driven detection and analysis of label-free protein aggregates

K. A. Ibrahim 

In this Tools of the Trade article, Khalid Ibrahim (Radenovic and Lashuel labs) describes a tool for the artificial intelligence (AI)-driven detection of cellular aggregates that bypasses the need for fluorescent labelling.

Resolution in super-resolution microscopy — definition, trade-offs and perspectives

Kirti Prakash; David Baddeley; Christian Eggeling; Reto Fiolka; Rainer Heintzmann et al. 

Super-resolution microscopy (SRM) is gaining popularity in biosciences; however, claims about optical resolution are contested and often misleading. In this Viewpoint, experts share their views on resolution and common trade-offs, such as labelling and post-processing, aiming to clarify them for biologists and facilitate deeper understanding and best use of SRM.

Fluorescence microscopy: A statistics-optics perspective

M. Fazel; K. S. Grussmayer; B. Ferdman; A. Radenovic; Y. Shechtman et al. 

Fundamental properties of light unavoidably impose features on images collected using fluorescence microscopes. Accounting for these features is often critical in quantitatively interpreting microscopy images, especially those gathering information at scales on par with or smaller than light’s emission wavelength. Here the optics responsible for generating fluorescent images, fluorophore properties, and microscopy modalities leveraging properties of both light and fluorophores, in addition to the necessarily probabilistic modeling tools imposed by the stochastic nature of light and measurement, are reviewed.

Label-Free Techniques for Probing Biomolecular Condensates

K. A. Ibrahim; A. S. Naidu; H. Miljkovic; A. Radenovic; W. Yang 

Biomolecular condensates play important roles in a wide array of fundamental biological processes, such as cellular compartmentalization, cellular regulation, and other biochemical reactions. Since their discovery and first observations, an extensive and expansive library of tools has been developed to investigate various aspects and properties, encompassing structural and compositional information, material properties, and their evolution throughout the life cycle from formation to eventual dissolution. This Review presents an overview of the expanded set of tools and methods that researchers use to probe the properties of biomolecular condensates across diverse scales of length, concentration, stiffness, and time. In particular, we review recent years’ exciting development of label-free techniques and methodologies. We broadly organize the set of tools into 3 categories: (1) imaging-based techniques, such as transmitted-light microscopy (TLM) and Brillouin microscopy (BM), (2) force spectroscopy techniques, such as atomic force microscopy (AFM) and the optical tweezer (OT), and (3) microfluidic platforms and emerging technologies. We point out the tools’ key opportunities, challenges, and future perspectives and analyze their correlative potential as well as compatibility with other techniques. Additionally, we review emerging techniques, namely, differential dynamic microscopy (DDM) and interferometric scattering microscopy (iSCAT), that have huge potential for future applications in studying biomolecular condensates. Finally, we highlight how some of these techniques can be translated for diagnostics and therapy purposes. We hope this Review serves as a useful guide for new researchers in this field and aids in advancing the development of new biophysical tools to study biomolecular condensates.

Exploring ion and analyte transport in beta-barrel forming biological nanopores

Optical imaging of molecules and their dynamics from surfaces to nanoscale confinement

Nature-inspired stalactite nanostructures such as nanopores for biosensing and energy harvesting

A. Chernev; Y. Teng; A. Radenovic 

A method of forming a structure, preferably a pore, comprises the steps of providing a template comprising at least one template aperture, and growing at least one material at an orifice of the template aperture by depositing the material, whereby the structure is formed.

Tunnel junction sensing of TATP explosive at the single-molecule level

A. Z. Tomovic; H. Miljkovic; M. S. Drazic; V. P. Jovanovic; R. Zikic 

Triacetone triperoxide (TATP) is a highly potent homemade explosive commonly used in terrorist attacks. Its detection poses a significant challenge due to its volatility, and the lack of portability of current sensing techniques. To address this issue, we propose a novel approach based on single-molecule TATP detection in the air using a device where tunneling current in N-terminated carbon-nanotubes nanogaps is measured. By employing the density functional theory combined with the non-equilibrium Green’s function method, we show that current of tens of nanoamperes passes through TATP trapped in the nanogap, with a discrimination ratio of several orders of magnitude even against prevalent indoor volatile organic compounds (VOCs). This high tunneling current through TATP’s highest occupied molecular orbital (HOMO) is facilitated by the strong electric field generated by N-C polar bonds at the electrode ends and by the hybridization between TATP and the electrodes, driven by oxygen atoms within the probed molecule. The application of the same principle is discussed for graphene nanogaps and break-junctions.|This DFT+NEGF study explores the sensing of the TATP explosive at a single molecule level. The real-time sensing via tunneling current measurement of a TATP molecule between N-terminated (3,3) CNT electrodes could be a solution for portable devices.

Confinement-Controlled Water Engenders Unusually High Electrochemical Capacitance

S. Melnik; A. Ryzhov; A. Kiselev; A. Radenovic; T. Weil et al. 

The electrodynamicsof nanoconfined water have been shownto changedramatically compared to bulk water, opening room for safe electrochemicalsystems. We demonstrate a nanofluidic “water-only” batterythat exploits anomalously high electrolytic properties of pure waterat firm confinement. The device consists of a membrane electrode assemblyof carbon-based nanomaterials, forming continuously interconnectedwater-filled nanochannels between the separator and electrodes. Theefficiency of the cell in the 1-100 nm pore size range showsa maximum energy density at 3 nm, challenging the region of the currentmetal-ion batteries. Our results establish the electrodynamic fundamentalsof nanoconfined water and pave the way for low-cost and inherentlysafe energy storage solutions that are much needed in the renewableenergy sector.

Selective Growth of van der Waals Heterostructures Enabled by Electron-Beam Irradiation

J. Sitek; K. Czerniak-Losiewicz; A. P. Gertych; M. Giza; P. Dabrowski et al. 

Van der Waals heterostructures (vdWHSs) enable the fabricationof complex electronic devices based on two-dimensional (2D) materials.Ideally, these vdWHSs should be fabricated in a scalable and repeatableway and only in the specific areas of the substrate to lower the numberof technological operations inducing defects and impurities. Here,we present a method of selective fabrication of vdWHSs via chemicalvapor deposition by electron-beam (EB) irradiation. We distinguishtwo growth modes: positive (2D materials nucleate on the irradiatedregions) on graphene and tungsten disulfide (WS2) substrates,and negative (2D materials do not nucleate on the irradiated regions)on the graphene substrate. The growth mode is controlled by limitingthe air exposure of the irradiated substrate and the time betweenirradiation and growth. We conducted Raman mapping, Kelvin-probe forcemicroscopy, X-ray photoelectron spectroscopy, and density-functionaltheory modeling studies to investigate the selective growth mechanism.We conclude that the selective growth is explained by the competitionof three effects: EB-induced defects, adsorption of carbon species,and electrostatic interaction. The method here is a critical steptoward the industry-scale fabrication of 2D-materials-based devices.

Nature-Inspired Stalactite Nanopores for Biosensing and Energy Harvesting

A. Chernev; Y. Teng; M. Thakur; V. Boureau; L. Navratilova et al. 

Nature provides a wide range of self-assembled structures from the nanoscale to the macroscale. Under the right thermodynamic conditions and with the appropriate material supply, structures like stalactites, icicles, and corals can grow. However, the natural growth process is time-consuming. This work demonstrates a fast, nature-inspired method for growing stalactite nanopores using heterogeneous atomic deposition of hafnium dioxide at the orifice of templated silicon nitride apertures. The stalactite nanostructures combine the benefits of reduced sensing region typically for 2-dimensional material nanopores with the asymmetric geometry of capillaries, resulting in ionic selectivity, stability, and scalability. The proposed growing method provides an adaptable nanopore platform for basic and applied nanofluidic research, including biosensing, energy science, and filtration technologies.