Streamlined Specimen Purification for Rapid COVID-19 Diagnosis Using Positively Charged Polymer Thin Film-Coated Surfaces and Chamber Digital PCR.

The ongoing coronavirus disease 2019 (COVID-19) pandemic demands rapid and straightforward diagnostic tools to prevent early-stage viral transmission. Although nasopharyngeal swabs are a widely used patient sample collection method for diagnosing COVID-19, using these samples for diagnosis without RNA extraction increases the risk of obtaining false-positive and -negative results. Thus, multiple purification steps are necessary, which are time-consuming, generate significant waste, and result in substantial sample loss. To address these issues, we developed surface-modified polymerase chain reaction (PCR) tubes using the tertiary aminated polymer poly(2-dimethylaminomethylstyrene) (pDMAMS) via initiated chemical vapor deposition. Introducing the clinical samples into the pDMAMS-coated tubes resulted in approximately 100% RNA capture efficiency within 25 min, which occurred through electrostatic interactions between the positively charged pDMAMS surface and the negatively charged RNA. The captured RNA is then detected via chamber digital PCR, enabling a sensitive, accurate, and rapid diagnosis. Our platform provides a simple and efficient RNA extraction and detection strategy that allows detection from 22 nasopharyngeal swabs and 21 saliva specimens with 0% false negatives. The proposed method can facilitate the diagnosis of COVID-19 and contribute to the prevention of early-stage transmission.

Polysaccharide-Polyplex Nanofilm Coatings Enhance Nanoneedle-Based Gene Delivery and Transfection Efficiency.

Non-viral vectors represent versatile and immunologically safer alternatives for nucleic acid delivery. Nanoneedles and high-aspect ratio nanostructures are unconventional but interesting delivery systems, in which delivery is mediated by surface interactions. Herein, nanoneedles are synergistically combined with polysaccharide-polyplex nanofilms and enhanced transfection efficiency is observed, compared to polyplexes in suspension. Different polyplex-polyelectrolyte nanofilm combinations are assessed and it is found that transfection efficiency is enhanced when using polysaccharide-based polyanions, rather than being only specific for hyaluronic acid, as suggested in earlier studies. Moreover, results show that enhanced transfection is not mediated by interactions with the CD44 receptor, previously hypothesized as a major mechanism mediating enhancement via hyaluronate. In cardiac tissue, nanoneedles are shown to increase the transfection efficiency of nanofilms compared to flat substrates; while in vitro, high transfection efficiencies are observed in nanostructures where cells present large interfacing areas with the substrate. The results of this study demonstrate that surface-mediated transfection using this system is efficient and safe, requiring amounts of nucleic acid with an order of magnitude lower than standard culture transfection. These findings expand the spectrum of possible polyelectrolyte combinations that can be used for the development of suitable non-viral vectors for exploration in further clinical trials.

Multiplex SNP Genotyping Using SWITCH: Sequence-Specific Nanoparticle with Interpretative Toehold-Mediated Sequence Decoding in Hydrogel.

Single nucleotide polymorphisms (SNPs) that can alter phenotypes of individuals play a pivotal role in disease development and, more importantly, responses to therapy. However, SNP genotyping has been challenging due to the similarity of SNP alleles and their low concentration in biological samples. Sequence-specific nanoparticle with interpretative toehold-mediated sequence decoding in hydrogel (SWITCH) for multiplex SNP genotyping is presented. The encoding with gold nanoparticle probes transduces each SNP target to ≈1000 invaders with prominently different sequences between wild and mutant types, featuring polymerase chain reaction (PCR)-free amplification. Subsequently, the toehold-mediated DNA replacement in hydrogel microparticles decodes the invaders via SNP-specific fluorescence signals. The 4-plex detection of the warfarin-associated SNP targets spiked in commercially validated human serum (S1-100ML, Merck) is successfully demonstrated with excellent specificity. This work is the first technology development presenting PCR-free, multiplex SNP genotyping with a single reporting fluorophore, to the best of knowledge.

Synthesis of ultrathin polymer insulating layers by initiated chemical vapour deposition for low-power soft electronics.

Insulating layers based on oxides and nitrides provide high capacitance, low leakage, high breakdown field and resistance to electrical stresses when used in electronic devices based on rigid substrates. However, their typically high process temperatures and brittleness make it difficult to achieve similar performance in flexible or organic electronics. Here, we show that poly(1,3,5-trimethyl-1,3,5-trivinyl cyclotrisiloxane) (pV3D3) prepared via a one-step, solvent-free technique called initiated chemical vapour deposition (iCVD) is a versatile polymeric insulating layer that meets a wide range of requirements for next-generation electronic devices. Highly uniform and pure ultrathin films of pV3D3 with excellent insulating properties, a large energy gap (>8 eV), tunnelling-limited leakage characteristics and resistance to a tensile strain of up to 4% are demonstrated. The low process temperature, surface-growth character, and solvent-free nature of the iCVD process enable pV3D3 to be grown conformally on plastic substrates to yield flexible field-effect transistors as well as on a variety of channel layers, including organics, oxides, and graphene.

Nanoscale surface coatings and topographies for neural interfaces.

With the lack of minimally invasive tools for probing neuronal systems across spatiotemporal scales, understanding the working mechanism of the nervous system and limited assessments available are imperative to prevent or treat neurological disorders. In particular, nanoengineered neural interfaces can provide a solution to this technological barrier. This review covers recent surface engineering approaches, including nanoscale surface coatings, and a range of topographies from the microscale to the nanoscale, primarily focusing on neural-interfaced biosystems. Specifically, the immobilization of bioactive molecules to fertilize the neural cell lineage, topographical engineering to induce mechanotransduction in neural cells, and enhanced cell-chip coupling using three-dimensional structured surfaces are highlighted. Advances in neural interface design will help us understand the nervous system, thereby achieving the effective treatments for neurological disorders. STATEMENT OF SIGNIFICANCE: • This review focuses on designing bioactive neural interface with a nanoscale chemical modification and topographical engineering at multiscale perspective. • Versatile nanoscale surface coatings and topographies for neural interface are summarized. • Recent advances in bioactive materials applicable for neural cell culture, electrophysiological sensing, and neural implants are reviewed.

High-Aspect-Ratio Nanostructured Surfaces as Biological Metamaterials.

Materials patterned with high-aspect-ratio nanostructures have features on similar length scales to cellular components. These surfaces are an extreme topography on the cellular level and have become useful tools for perturbing and sensing the cellular environment. Motivation comes from the ability of high-aspect-ratio nanostructures to deliver cargoes into cells and tissues, access the intracellular environment, and control cell behavior. These structures directly perturb cells' ability to sense and respond to external forces, influencing cell fate, and enabling new mechanistic studies. Through careful design of their nanoscale structure, these systems act as biological metamaterials, eliciting unusual biological responses. While predominantly used to interface eukaryotic cells, there is growing interest in nonanimal and prokaryotic cell interfacing. Both experimental and theoretical studies have attempted to develop a mechanistic understanding for the observed behaviors, predominantly focusing on the cell-nanostructure interface. This review considers how high-aspect-ratio nanostructured surfaces are used to both stimulate and sense biological systems.

Size-Tunable Nanoneedle Arrays for Influencing Stem Cell Morphology, Gene Expression, and Nuclear Membrane Curvature.

High-aspect-ratio nanostructures have emerged as versatile platforms for intracellular sensing and biomolecule delivery. Here, we present a microfabrication approach in which a combination of reactive ion etching protocols were used to produce high-aspect-ratio, nondegradable silicon nanoneedle arrays with tip diameters that could be finely tuned between 20 and 700 nm. We used these arrays to guide the long-term culture of human mesenchymal stem cells (hMSCs). Notably, we used changes in the nanoneedle tip diameter to control the morphology, nuclear size, and F-actin alignment of interfaced hMSCs and to regulate the expression of nuclear lamina genes, Yes-associated protein (YAP) target genes, and focal adhesion genes. These topography-driven changes were attributed to signaling by Rho-family GTPase pathways, differences in the effective stiffness of the nanoneedle arrays, and the degree of nuclear membrane impingement, with the latter clearly visualized using focused ion beam scanning electron microscopy (FIB-SEM). Our approach to design high-aspect-ratio nanostructures will be broadly applicable to design biomaterials and biomedical devices used for long-term cell stimulation and monitoring.

Surface enhanced Raman scattering artificial nose for high dimensionality fingerprinting.

Label-free surface-enhanced Raman spectroscopy (SERS) can interrogate systems by directly fingerprinting their components' unique physicochemical properties. In complex biological systems however, this can yield highly overlapping spectra that hinder sample identification. Here, we present an artificial-nose inspired SERS fingerprinting approach where spectral data is obtained as a function of sensor surface chemical functionality. Supported by molecular dynamics modeling, we show that mildly selective self-assembled monolayers can influence the strength and configuration in which analytes interact with plasmonic surfaces, diversifying the resulting SERS fingerprints. Since each sensor generates a modulated signature, the implicit value of increasing the dimensionality of datasets is shown using cell lysates for all possible combinations of up to 9 fingerprints. Reliable improvements in mean discriminatory accuracy towards 100% are achieved with each additional surface functionality. This arrayed label-free platform illustrates the wide-ranging potential of high-dimensionality artificial-nose based sensing systems for more reliable assessment of complex biological matrices.

Porous Silicon Nanoneedles Modulate Endocytosis to Deliver Biological Payloads.

Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles, are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane-nanoneedle interface. In particular, the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largely unexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, it is shown that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin-coated pits and caveolae. Nanoneedles enhance the internalization of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae- and clathrin-mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle-mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell-manipulation technologies.

Highly stacked 3D organic integrated circuits with via-hole-less multilevel metal interconnects.

Multilevel metal interconnects are crucial for the development of large-scale organic integrated circuits. In particular, three-dimensional integrated circuits require a large number of vertical interconnects between layers. Here, we present a novel multilevel metal interconnect scheme that involves solvent-free patterning of insulator layers to form an interconnecting area that ensures a reliable electrical connection between two metals in different layers. Using a highly reliable interconnect method, the highest stacked organic transistors to date, a three-dimensional organic integrated circuits consisting of 5 transistors and 20 metal layers, is successfully fabricated in a solvent-free manner. All transistors exhibit outstanding device characteristics, including a high on/off current ratio of ~107, no hysteresis behavior, and excellent device-to-device uniformity. We also demonstrate two vertically-stacked complementary inverter circuits that use transistors on 4 different floors. All circuits show superb inverter characteristics with a 100% output voltage swing and gain up to 35 V per V.

Organic flash memory on various flexible substrates for foldable and disposable electronics.

With the emergence of wearable or disposable electronics, there grows a demand for a flash memory realizable on various flexible substrates. Nevertheless, it has been challenging to develop a flash memory that simultaneously exhibits a significant level of flexibility and performance. This is mainly due to the scarcity of flexible dielectric materials with insulating properties sufficient for a flash memory, which involves dual dielectric layers, respectively, responsible for tunneling and blocking of charges. Here we report ultra-flexible organic flash memories based on polymer dielectrics prepared by initiated chemical vapor deposition. Using their near-ideal dielectric characteristics, we demonstrate flash memories bendable down to a radius of 300 µm that exhibits a relatively long-projected retention with a programming voltage on par with the present industrial standards. The proposed memory technology is then applied to non-conventional substrates, such as papers, to demonstrate its feasibility in a wide range of applications.Flexible flash memory is crucial to modern electronics, but its fabrication is challenging in the absence of suitable dielectric materials. Here, Lee et al. realize organic memory with retention over 10 years using tunneling and blocking dielectric layers prepared by initiated chemical vapor deposition.

Flexible, Low-Power Thin-Film Transistors Made of Vapor-Phase Synthesized High-k, Ultrathin Polymer Gate Dielectrics.

A series of high-k, ultrathin copolymer gate dielectrics were synthesized from 2-cyanoethyl acrylate (CEA) and di(ethylene glycol) divinyl ether (DEGDVE) monomers by a free radical polymerization via a one-step, vapor-phase, initiated chemical vapor deposition (iCVD) method. The chemical composition of the copolymers was systematically optimized by tuning the input ratio of the vaporized CEA and DEGDVE monomers to achieve a high dielectric constant (k) as well as excellent dielectric strength. Interestingly, DEGDVE was nonhomopolymerizable but it was able to form a copolymer with other kinds of monomers. Utilizing this interesting property of the DEGDVE cross-linker, the dielectric constant of the copolymer film could be maximized with minimum incorporation of the cross-linker moiety. To our knowledge, this is the first report on the synthesis of a cyanide-containing polymer in the vapor phase, where a high-purity polymer film with a maximized dielectric constant was achieved. The dielectric film with the optimized composition showed a dielectric constant greater than 6 and extremely low leakage current densities (<3 × 10-8 A/cm2 in the range of ±2 MV/cm), with a thickness of only 20 nm, which is an outstanding thickness for down-scalable cyanide polymer dielectrics. With this high-k dielectric layer, organic thin-film transistors (OTFTs) and oxide TFTs were fabricated, which showed hysteresis-free transfer characteristics with an operating voltage of less than 3 V. Furthermore, the flexible OTFTs retained their low gate leakage current and ideal TFT characteristics even under 2% applied tensile strain, which makes them some of the most flexible OTFTs reported to date. We believe that these ultrathin, high-k organic dielectric films with excellent mechanical flexibility will play a crucial role in future soft electronics.

Efficient organic photomemory with photography-ready programming speed.

We propose a device architecture for a transistor-type organic photomemory that can be programmed fast enough for use in electrical photography. Following the strategies used in a flash memory where an isolated charge storage node or floating gate is employed, the proposed organic photomemory adopts an isolated photo-absorption zone that is embedded between upper and lower insulator layers without directly interfacing with a semiconductor channel layer. This isolated photo-absorption zone then allows the device to operate in electrically 'on' state, in which the high electric-field region can have a maximal spatial overlap with the illuminated area for efficient and facile light-programming. With the proposed approach, a significant threshold voltage shift is attained even with the exposure time as short as 5 ms. High quality dielectric layers prepared by initiated chemical vapor deposition ensure erasing to occur only with electrical signal in a controlled manner. Retention time up to 700 s is demonstrated.

Flexible Nonvolatile Polymer Memory Array on Plastic Substrate via Initiated Chemical Vapor Deposition.

Resistive random access memory based on polymer thin films has been developed as a promising flexible nonvolatile memory for flexible electronic systems. Memory plays an important role in all modern electronic systems for data storage, processing, and communication; thus, the development of flexible memory is essential for the realization of flexible electronics. However, the existing solution-processed, polymer-based RRAMs have exhibited serious drawbacks in terms of the uniformity, electrical stability, and long-term stability of the polymer thin films. Here, we present poly(1,3,5-trimethyl-1,3,5-trivinyl cyclotrisiloxane) (pV3D3)-based RRAM arrays fabricated via the solvent-free technique called initiated chemical vapor deposition (iCVD) process for flexible memory application. Because of the outstanding chemical stability of pV3D3 films, the pV3D3-RRAM arrays can be fabricated by a conventional photolithography process. The pV3D3-RRAM on flexible substrates showed unipolar resistive switching memory with an on/off ratio of over 10(7), stable retention time for 10(5) s, excellent cycling endurance over 10(5) cycles, and robust immunity to mechanical stress. In addition, pV3D3-RRAMs showed good uniformity in terms of device-to-device distribution. The pV3D3-RRAM will pave the way for development of next-generation flexible nonvolatile memory devices.

Foldable and Disposable Memory on Paper.

Foldable organic memory on cellulose nanofibril paper with bendable and rollable characteristics is demonstrated by employing initiated chemical vapor deposition (iCVD) for polymerization of the resistive switching layer and inkjet printing of the electrode, where iCVD based on all-dry and room temperature process is very suitable for paper electronics. This memory exhibits a low operation voltage of 1.5 V enabling battery operation compared to previous reports and wide memory window. The memory performance is maintained after folding tests, showing high endurance. Furthermore, the quick and complete disposable nature demonstrated here is attractive for security applications. This work provides an effective platform for green, foldable and disposable electronics based on low cost and versatile materials.

Photolithography-Based Patterning of Liquid Metal Interconnects for Monolithically Integrated Stretchable Circuits.

We demonstrate a new patterning technique for gallium-based liquid metals on flat substrates, which can provide both high pattern resolution (∼20 µm) and alignment precision as required for highly integrated circuits. In a very similar manner as in the patterning of solid metal films by photolithography and lift-off processes, the liquid metal layer painted over the whole substrate area can be selectively removed by dissolving the underlying photoresist layer, leaving behind robust liquid patterns as defined by the photolithography. This quick and simple method makes it possible to integrate fine-scale interconnects with preformed devices precisely, which is indispensable for realizing monolithically integrated stretchable circuits. As a way for constructing stretchable integrated circuits, we propose a hybrid configuration composed of rigid device regions and liquid interconnects, which is constructed on a rigid substrate first but highly stretchable after being transferred onto an elastomeric substrate. This new method can be useful in various applications requiring both high-resolution and precisely aligned patterning of gallium-based liquid metals.

Logic circuits composed of flexible carbon nanotube thin-film transistor and ultra-thin polymer gate dielectric.

Printing electronics has become increasingly prominent in the field of electronic engineering because this method is highly efficient at producing flexible, low-cost and large-scale thin-film transistors. However, TFTs are typically constructed with rigid insulating layers consisting of oxides and nitrides that are brittle and require high processing temperatures, which can cause a number of problems when used in printed flexible TFTs. In this study, we address these issues and demonstrate a method of producing inkjet-printed TFTs that include an ultra-thin polymeric dielectric layer produced by initiated chemical vapor deposition (iCVD) at room temperature and highly purified 99.9% semiconducting carbon nanotubes. Our integrated approach enables the production of flexible logic circuits consisting of CNT-TFTs on a polyethersulfone (PES) substrate that have a high mobility (up to 9.76 cm(2) V(-1) sec(-)1), a low operating voltage (less than 4 V), a high current on/off ratio (3 × 10(4)), and a total device yield of 90%. Thus, it should be emphasized that this study delineates a guideline for the feasibility of producing flexible CNT-TFT logic circuits with high performance based on a low-cost and simple fabrication process.

Direct Observation of a Carbon Filament in Water-Resistant Organic Memory.

The memory for the Internet of Things (IoT) requires versatile characteristics such as flexibility, wearability, and stability in outdoor environments. Resistive random access memory (RRAM) to harness a simple structure and organic material with good flexibility can be an attractive candidate for IoT memory. However, its solution-oriented process and unclear switching mechanism are critical problems. Here we demonstrate iCVD polymer-intercalated RRAM (i-RRAM). i-RRAM exhibits robust flexibility and versatile wearability on any substrate. Stable operation of i-RRAM, even in water, is demonstrated, which is the first experimental presentation of water-resistant organic memory without any waterproof protection package. Moreover, the direct observation of a carbon filament is also reported for the first time using transmission electron microscopy, which puts an end to the controversy surrounding the switching mechanism. Therefore, reproducibility is feasible through comprehensive modeling. Furthermore, a carbon filament is superior to a metal filament in terms of the design window and selection of the electrode material. These results suggest an alternative to solve the critical issues of organic RRAM and an optimized memory type suitable for the IoT era.