Aptamers face challenges for use outside the ideal conditions in which they are developed. These difficulties are most palpable in vivo due to nuclease activities, rapid clearance, and off-target binding. Herein, we demonstrate that a polyphosphodiester-backboned molecular brush can suppress enzymatic digestion, reduce non-specific cell uptake, enable long blood circulation, and rescue the bioactivity of a conjugated aptamer in vivo. The backbone along with the aptamer is assembled via solid-phase synthesis, followed by installation of poly(ethylene glycol) (PEG) side chains using a two-step process with near-quantitative efficiency. The synthesis allows for precise control over polymer size and architecture. Consisting entirely of building blocks that are generally recognized as safe for therapeutics, this novel molecular brush is expected to provide a highly translatable route for aptamer-based therapeutics.

The application of nanopores as label-free, single-molecule biosensors for electrical or optical probing of structural features in biomolecules has been widely explored. While biological nanopores (membrane proteins and bacteriophage portal proteins) and solid-state nanopores (thin films and two-dimensional materials) have been extensively employed, the third class of nanopores known as hybrid nanopores, where an artificial membrane substitutes the organic support membrane of proteins, has been only sparsely studied due to challenges in implementation. G20c portal protein contains a natural DNA pore that is used by viruses for filling their capsid with viral genomic DNA. We have previously developed a lipid-free hybrid nanopore by "corking" the G20c portal protein into a SiNx nanopore. Herein, we demonstrate that through chemical functionalization of the synthetic nanopore, covalent linkage between the solid-state pore and the G20c portal protein considerably improves the hybrid pore stability, lifetime, and voltage resilience. Moreover, we demonstrate electric-field-driven and motor protein-mediated transport of DNA molecules through this hybrid nanopore. Our integrated protein/solid-state device can serve as a robust and durable framework for sensing and sequencing at high voltages, potentially providing higher resolution, higher signal-to-noise ratio, and higher throughput compared to the more conventional membrane-embedded protein platforms.

The chemical reactions involved in the decomposition of 9-hydroxyellipticine (9-OH-E), an anticancer agent, in polar solvents is explained. The reactions, which involve the formation of 9-oxo-ellipticine and the addition of a nucleophilic acid on the C10 site of the heterocyclic system, have been used to measure 9-OH-E quantitatively by colorimetry in solution and by reflection on paper surfaces. A method for the stabilization of 9-OH-E in polar solvents is proposed.

Developing techniques for the high-quality synthesis of mono and few-layered two-dimensional (2D) materials with lowered complexity and cost continues to remain an important goal, both for accelerating fundamental research and for application development. We present the simplest conceivable technique to synthesize micrometer-scale single-crystal, less than 1 nm thick, triangular monolayers of MoS2, i.e., by direct heating of bulk MoS2 powder onto proximally placed substrates. Room-temperature excitonic line width values of our samples are narrower and more uniform than those of 2D-MoS2 obtained by most other techniques reported in literature, and comparable to those of ultraflat boronnitride (h-BN)-capped mechanically exfoliated samples, indicative of their high quality. Feature-rich Raman spectra absent in samples grown or obtained by most other techniques, also stand out as a testament of the high quality of our samples. A contact-growth mode facilitates direct growth of crystallographically wrinkled circular samples, which allows us to directly compare the optoelectronic properties of flat vs wrinkled growth from the same growth runs. Our method allows, for the first time, to quantitatively compare the impact of wrinkle on excitonic and Raman peak positions on identically synthesized 2D-MoS2. Wrinkles lead to average red shifts of similar to 30 meV in the A-exciton position and similar to 2 cm(-1) in the E-2g(1) Raman peak in these samples. Our findings open up several possibilities that expand 2D material research. By eliminating the need for carrier-gas flow, mechanical motion, or chemical reactions, our method can be either miniaturized for substantially low-cost, high-quality scientific research or potentially scaled-up for the mass-production of 2D crystals for commercial purposes. Moreover, we believe that this technique can also be extended to other transition metal dichalcogenides and other layered materials, providing scientists and engineers a low-cost platform for advancing research in sensing, detection, and fundamental discoveries.

Two-dimensional (2D) heterostructured electrodes built from vertical stacking of different 2D materials are among the most promising electrode architectures for electrochemical energy storage devices. These materials offer interesting opportunities for energy storage applications such as versatility in the structural design of electrode, and the possibility to integrate individual 2D building blocks with different properties into heterostructures. These features can potentially enable new materials with improved or new electrochemical features. Here, we report on large-scale liquid phase self-assembly of 2D heterostructures built from two different 2D transition metal carbides (MXenes), Ti3C2Tx and V2CTx. A cation-driven self-assembly process was used to assemble the negatively-charged flakes of the two MXenes into heterolayered flakes. The freestanding and binder-free MXene heterostructure films could deliver a high volumetric capacitance of similar to 1473 F cm(-3) and showed no capacitance loss after 50,000 charge-discharge cycles in 3 M H2SO4 electrolyte. Due to coupling of redox reactions of Ti3C2Tx and V2CTx, the heterostructure electrodes showed a nearly constant current over their entire potential window, which is reminiscent of traditional pseudocapacitive materials. This electrochemical behavior differs from individual MXene electrodes or most other emerging pseudocapacitive materials whose maximum performance is usually achieved in a narrow potential range.

Bottom-up assembly of two-dimensional (2D) materials into macroscale morphologies with emergent properties requires control of the material surroundings, so that energetically favorable conditions direct the assembly process. MXenes, a class of recently developed 2D materials, have found new applications in areas such as electrochemical energy storage, nanoscale electronics, sensors, and biosensors. In this paper, we present a lateral self-assembly method for wafer-scale deposition of a mosaic-type 2D MXene flake monolayer that spontaneously orders at the interface between two immiscible solvents. ReaxFF molecular dynamics simulations elucidate the interactions of a MXene flake with the solvents and its stability at the liquid/liquid interface, the prerequisite for MXene flakes self-assembly at the interface. Moreover, facile transfer of this monolayer onto a flat substrate (Si, glass) results in high-coverage monolayer films with uniform thickness and homogeneous optical properties. Multiscale characterization of the resulting films reveals the mosaic structure and sheds light on the electronic properties of the films, which exhibit good electrical conductivity over cm-scale areas.

In the last two decades, nanopore technology has revolutionized the single-molecule study of biomolecules by providing researchers with an inexpensive, rapid, and high-throughput tool for various biophysical studies. What was initiated as an idea for sequencing DNA by threading it through a tiny hole has evolved into not only a commercially available product for direct DNA and RNA sequencing, but also a prevalent tool in biophysics with applications spanning from studying biomolecular interactions, force spectroscopy, and single-molecule mass spectrometry to protein sequencing currently on its horizon. Nonetheless, certain gaps remain to be filled to further advance this technology in terms of resolution, device integrity, and high-yield, large-scale device fabrication. These gaps prevent the full exploitation of this technology for high-resolution sensing and sequencing applications. This Ph.D. work aimed to develop two novel nanopore platforms; although different in nature, their unique designs overcome several existing drawbacks and offer new possibilities in single-molecule nanopore technology. The first part of this Ph.D. dissertation is focused on a two-dimensional material (2D)-based nanopore platform based on an emerging family of 2D materials known as MXenes. Through serial steps of research and study, namely implementing MXene nanopores for biomolecular study, developing large-scale MXene monolayer film fabrication, and exploring actuation properties of MXene nanopores, we developed a new nanopore sensing concept by harnessing unique electrical and electrochemical properties of MXenes and their versatile chemistry. This new nanopore sensing paradigm could provide higher resolution than the commercially available technologies. The second part of this Ph.D. dissertation focuses on an integrated synthetic/biological hybrid nanopore platform by immobilizing a DNA transporter protein within a thin synthetic membrane to form a robust and durable framework for sensing and sequencing at high voltages with a potential to provide higher resolution and throughput. The outcome of this Ph.D. research will directly or indirectly open new venues in expanding the capabilities of nanopore technology and the development of new nanopore systems based on them. --Author's abstract

Site-specific, reproducible, and uniform-orientation protein immobilization on an inorganic surface while preserving protein conformation and activity is of wide interest for applications in biosensing, protein microarrays, and enzymology, among others. Successful immobilization requires understanding of material's surface chemistry, protein properties, and nature of their interaction to eliminate non-specific binding. Portal protein is a naturally occurring pore (biological nanopore) and part of the bacteriophage packaging machine that pumps the viral genome inside its capsid. In this work, we have explored different approaches to immobilize G20c portal protein from double-stranded bacteriophage G20c into a thin (∼30 nm) silicon nitride (SiNx) membrane embedded in a silicon chip. Desired orientation of the immobilized protein is achieved by maintaining a voltage bias across the membrane to electrokinetically drive a single protein into the synthetic nanopore. The nanopore geometry dictates a predominant favorable protein orientation while the portal preserves its conformation, as indicated by ion current measurements through the “hybrid nanopore”. Application of nanopores (both synthetic and biological) as label-free, single-molecule biosensors for electrical and/or optical probing of structural features in biomolecules have been widely explored. Confirmed by our single-molecule electrical sensing results, our hybrid nanopore system provides mechanically robust and chemically compatible synthetic protein framework, superior to its natural counterparts such as organic membranes (lipid bilayer, for example), and exploits tunable and engineerable characteristics of thermostable G20c portal protein rendering an active, high-resolution biomolecule sensing platform. We demonstrate here through chemical functionalization of synthetic nanopores and/or engineering G20c portal protein assemblies, a protein nanopore chemically linked to a synthetic nanopore, rendering considerably improved protein stability, sensing lifetime, and signal-to-noise ratio compared to our previous hybrid system. This development will be widely applicable to coupled nanopore sensor arrangements such as electro-optical and electro-pressure systems.

Developing techniques for high-quality synthesis of mono and few-layered 2D materials with lowered complexity and cost continues to remain an important goal, both for accelerating fundamental research and for applications development. We present the simplest conceivable technique to synthesize micrometer-scale single-crystal triangular monolayers of MoS2, i.e. by direct heating of bulk MoS2 powder onto proximally-placed substrates. Room-temperature excitonic linewidth values of our samples are narrower and more uniform than those of 2D-MoS2 obtained by most other techniques reported in literature, and comparable to those of ultraflat h-BN-capped mechanically exfoliated samples, indicative of their high quality. Feature-rich Raman spectra absent in samples grown or obtained by most other techniques, also stand out as a testament of the high quality of our samples. A contact-growth mode facilitates direct growth of crystallographically-strained circular samples, which allows us to directly compare the optoelectronic properties of flat vs. strained growth from the same growth runs. Our method allows, for the first time, to quantitatively compare the impact of strain on excitonic and Raman peak positions on identically-synthesized 2D-MoS2. Strain leads to average Red-shifts of ~ 30 meV in the A-exciton position, and ~ 2 cm-1 in the E12g Raman peak in these samples. Our findings open-up several new possibilities that expand 2D material research. By eliminating the need for carrier gas flow, mechanical motion or chemical reactions, our method can be either miniaturized for substantially low-cost, high-quality scientific research or potentially scaled-up for mass-production of 2D crystals for commercial purposes. Moreover, we believe this technique can also be extended to other transition metal dichalcogenides and other layered materials.

Label-free nanopore technology for sequencing biopolymers such as DNA and RNA could potentially replace existing methods if improvements in cost, speed, and accuracy are achieved. Solid-state nanopores have been developed over the past two decades as physically and chemically versatile sensors that mimic biological channels, through which transport and sequencing of biomolecules have already been demonstrated. Of particular interest is the use of two-dimensional (2D) materials as nanopore substrates, since these can in theory provide the highest resolution readout (<1 nm of a biopolymer segment) and opportunities for electronic multiplexed readout through their interesting electronic properties. In this work, we report on nanopores comprising atomically thin flakes of 2D transition metal carbides called MXenes. We demonstrate a high-yield (60%), contamination-free, and alignment-free transfer method that involves their self-assembly at a liquid-liquid interface to large-scale (mm-sized) films composed of sheets, followed by nanopore fabrication using focused electron beams. Our work demonstrates the feasibility of MXenes, a class of hydrophilic 2D materials with over 20 compositions known to date, as nanopore membranes for DNA translocation and single-molecule sensing applications.

In article number 1806931, flexible and freestanding films of 2D vanadium carbide MXene (V2CTx) are prepared by Majid Beidaghi and co-workers and used as pseudocapacitive electrodes. The assembled films show excellent chemical and electrochemical stability in contrast to delaminated 2D V2CTx sheets, which rapidly oxidize in ambient conditions. The electrodes show exceptional high-rate pseudocapacitive properties in supercapacitors with aqueous electrolytes and can intercalate a variety of cations, delivering capacitances in excess of 1300 F cm−3 and a capacitance retention of ≈77% after one million charge–discharge cycles.

Nanometer-sized pores (nanopores) have emerged as a novel single-molecule detection technique to probe biomolecules (protein, DNA, and RNA) electrically and/or optically whilst being threaded into the pore. Since then, naturally-occurring pores known as biological nanopores (membrane proteins and bacteriophage portal proteins) along with synthetically-assembled nanopores known as solid-state nanopores have been employed to study various biomolecular characteristics. A third class of nanopores, known as hybrid nanopores, exploits the robust framework and mechanical stability of SS nanopores with atomically reproducible and tunable characteristics of biological nanopores. Biological nanopores supported by robust synthetic membrane eliminates fragility of lipid bilayers and arbitrary geometry of SS nanopores. Our group recently demonstrated the lipid insertion and stable formation of hydrophilic G20C portal protein transmembrane channels, derived from the G20C thermostable virus. Herein, we demonstrate the improved performance of our system by substituting the lipid bilayer support of the protein by thin SiNx free-standing membrane and making further modifications to chemically fix the protein on the membrane support. Finally, we report the application of our hybrid system in nanopore-based sensing of biomolecules.

Electrochemical capacitors (ECs) that store charge based on the pseudocapacitive mechanism combine high energy densities with high power densities and rate capabilities. 2D transition metal carbides (MXenes) have been recently introduced as high-rate pseudocapacitive materials with ultrahigh areal and volumetric capacitances. So far, 20 different MXene compositions have been synthesized and many more are theoretically predicted. However, since most MXenes are chemically unstable in their 2D forms, to date only one MXene composition, Ti3 C2 Tx , has shown stable pseudocapacitive charge storage. Here, a cation-driven assembly process is demonstrated to fabricate highly stable and flexible multilayered films of V2 CTx and Ti2 CTx MXenes from their chemically unstable delaminated single-layer flakes. The electrochemical performance of electrodes fabricated using assembled V2 CTx flakes surpasses Ti3 C2 Tx in various aqueous electrolytes. These electrodes show specific capacitances as high as 1315 F cm-3 and retain ≈77% of their initial capacitance after one million charge/discharge cycles, an unprecedented performance for pseudocapacitive materials. This work opens a new venue for future development of high-performance supercapacitor electrodes using a variety of 2D materials as building blocks.

Nanopore-based sensors are advancing the sensitivity and selectivity of single-molecule detection in molecular medicine and biotechnology. Current electrical sensing devices are based on either membrane protein pores supported in planar lipid bilayers or solid-state (SS) pores fabricated in thin metallic membranes. While both types of nanosensors have been used in a variety of applications, each has inherent disadvantages that limit its use. Hybrid nanopores, consisting of a protein pore supported within a SS membrane, combine the robust nature of SS membranes with the precise and simple engineering of protein nanopores. We demonstrate here a novel lipid-free hybrid nanopore comprising a natural DNA pore from a thermostable virus, electrokinetically inserted into a larger nanopore supported in a silicon nitride membrane. The hybrid pore is stable and easy to fabricate, and, most importantly, exhibits low peripheral leakage allowing sensing and discrimination among different types of biomolecules.

Nanopore-based sensors for nucleic acid sequencing and single-molecule detection typically employ pore-forming membrane proteins with hydrophobic external surfaces, suitable for insertion into a lipid bilayer. In contrast, hydrophilic pore containing molecules, such as DNA origami, have been shown to require chemical modification to favor insertion into a lipid environment. In this work, we describe a strategy for inserting polar proteins with an inner pore into lipid membranes, focusing here on a circular 12-subunit assembly of the thermophage G20c portal protein. X-ray crystallography, electron microscopy, molecular dynamics, and thermal/chaotrope denaturation experiments all find the G20c portal protein to have a highly stable structure, favorable for nanopore sensing applications. Porphyrin conjugation to a cysteine mutant in the protein facilitates the protein's insertion into lipid bilayers, allowing us to probe ion transport through the pore. Finally, we probed the portal interior size and shape using a series of cyclodextrins of varying sizes, revealing asymmetric transport that possibly originates from the portal's DNA-ratchet function.

This study addresses the role of PANI–CA composites in the detection of acetone vapors with high sensitivity and selectivity in the presence of alcohols. The PANI–CA composites were fabricated by the solution-casting method and were cut to 4 cm × 3 mm rectangular strips of about 20-μm thickness. The composite strips behave as gas sensors/chemoactuators and respond to gaseous species by converting their relative concentration to a corresponding mechanical motion (bending). The bending-recovery responses of PANI/CA sensor was examined thoroughly by exposing it to varying headspace concentrations of acetone and alcohols, and by removing the analyte once the sensor reached its maximum bending angle. Sensitivity was determined by comparing the bending response of the composite strips to different headspace concentrations of acetone. Selectivity was determined through analysis of the angle change in 50/50 ml solutions of four different (potentially interfering) chemicals. The results indicate that the sensor highly discriminates between acetone and alcohols making it a potential wearable acetone skin sensor for indirect measurement of glucose in the blood for diabetics.