CRISPR/Cas12a antifouling nanocomposite electrochemical biosensors enable amplification-free detection of Monkeypox virus in complex biological fluids.

The escalating global threat of infectious diseases, including monkeypox virus (MPXV), necessitates advancements in point-of-care diagnostics, moving beyond the constraints of conventional methods tethered to centralized laboratories. Here, we introduce multiple CRISPR RNA (crRNA)-based biosensors that can directly detect MPXV within 35 minutes without pre-amplification, leveraging the enhanced sensitivity and antifouling attributes of the BSA-based nanocomposite. Multiple crRNAs, strategically targeting diverse regions of the F3L gene of MPXV, are designed and combined to amplify Cas12a activation and its collateral cleavage of reporter probes. Notably, our electrochemical sensors exhibit the detection limit of 669 fM F3L gene without amplification, which is approximately a 15-fold improvement compared to fluorescence detection. This sensor also shows negligible changes in peak current after exposure to complex biological fluids, such as whole blood and serum, maintaining its sensitivity at 682 fM. This sensitivity is nearly identical to the conditions when only the F3L gene was present in PBS. In summary, our CRISPR-based electrochemical biosensors can be utilized as a high-performance diagnostic tool in resource-limited settings, representing a transformative leap forward in point-of-care testing. Beyond infectious diseases, the implications of this technology extend to various molecular diagnostics, establishing itself as a rapid, accurate, and versatile platform for detection of target analytes.

Noninvasive wearable sensor for the continuous monitoring of human sound and movement signals in real-time.

Recently, with the development of non-invasive human health monitoring technology including wearable devices, a flexible sensor that monitors 'human sound and movement signals' such as human voice and muscle movement is attracting attention. In this experiment, electrospun nanofibers were mixed with highly conductive nanoparticles and coated with polyaniline to detect the patient's electrical signals. Due to the high piezoelectric effect, nanofiber-based sensors do not require charging through a separate battery, so they can be used as self-powered devices. In addition, the LCR meter test confirmed that the sensor has a high capacitance due to its high conductivity and high sensitivity to electrical signals. The sensor produced in this study can visually estimate the electrical signal of the actual human body through real-time comparison with electromyography (EMG) measuring equipment, and it was confirmed that the error is small. This sensor is expected to be widely used in the medical field, from simple sound and movement signals to disease monitoring.

Micrometer-thick and porous nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties.

Development of coating technologies for electrochemical sensors that consistently exhibit antifouling activities in diverse and complex biological environments over extended time is vital for effective medical devices and diagnostics. Here, we describe a micrometer-thick, porous nanocomposite coating with both antifouling and electroconducting properties that enhances the sensitivity of electrochemical sensors. Nozzle printing of oil-in-water emulsion is used to create a 1 micrometer thick coating composed of cross-linked albumin with interconnected pores and gold nanowires. The layer resists biofouling and maintains rapid electron transfer kinetics for over one month when exposed directly to complex biological fluids, including serum and nasopharyngeal secretions. Compared to a thinner (nanometer thick) antifouling coating made with drop casting or a spin coating of the same thickness, the thick porous nanocomposite sensor exhibits sensitivities that are enhanced by 3.75- to 17-fold when three different target biomolecules are tested. As a result, emulsion-coated, multiplexed electrochemical sensors can carry out simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid, antigen, and host antibody in clinical specimens with high sensitivity and specificity. This thick porous emulsion coating technology holds promise in addressing hurdles currently restricting the application of electrochemical sensors for point-of-care diagnostics, implantable devices, and other healthcare monitoring systems.

Self-Mixed Biphasic Liquid Metal Composite with Ultra-High Stretchability and Strain-Insensitivity for Neuromorphic Circuits.

Neuromorphic circuits that can function under extreme deformations are important for various data-driven wearable and robotic applications. Herein, biphasic liquid metal particle (BMP) with unprecedented stretchability and strain-insensitivity (ΔR/R0 = 1.4@ 1200% strain) is developed to realize a stretchable neuromorphic circuit that mimics a spike-based biologic sensory system. The BMP consists of liquid metal particles (LMPs) and rigid liquid metal particles (RLMPs), which are homogeneously mixed via spontaneous solutal-Marangoni mixing flow during coating. This permits facile single step patterning directly on various substrates at room temperature. BMP is highly conductive (2.3 × 106 S/m) without any post activation steps. BMP interconnects are utilized for a sensory system, which is capable of distinguishing variations of biaxial strains with a spiking neural network, thus demonstrating their potential for various sensing and signal processing applications.

Ultrathin Mixed Ionic-Electronic Conducting Interlayer via the Solution Shearing Technique for High-Performance Lithium-Sulfur Batteries.

The commercialization of lithium-sulfur (Li-S) batteries has been hampered by diverse challenges, including the shuttle phenomenon and low electrical/ionic conductivity of lithium sulfide and sulfur. To address these issues, extensive research has been devoted to developing multifunctional interlayers. However, interlayers capable of simultaneously suppressing the polysulfide (PS) shuttle and ensuring stable electrical and ionic conductivity are relatively uncommon. Moreover, the use of thick and heavy interlayers results in an unavoidable decline in the energy density of Li-S batteries. We developed an ultrathin (750 nm), lightweight (0.182 mg cm-2) interlayer that facilitates mixed ionic-electronic conduction using the solution shearing technique. The interlayer, composed of carbon nanotube (CNT)/Nafion/poly-3,4-ethylenedioxythiophene:tetracyanoborate (PEDOT:TCB), effectively suppresses the shuttle phenomenon through the synergistic segregation and adsorption effects on PSs by Nafion and CNT/PEDOT, respectively. Furthermore, the electrical/ionic conductivity of the interlayer can be improved via counterion exchange and homogeneous Li+ ion flux/good wettability from SO3- functional group of Nafion, respectively. Enhanced sulfur utilization and reaction kinetics through polysulfide shuttle inhibition and facilitated electron/ion transfer by interlayer enable a high discharge capacity of 1029 mA h g-1 in the Li-S pouch cell under a high sulfur loading of 5.3 mg cm-2 and low electrolyte/sulfur ratio of 5 µL mg-1.

Deep-Learning Algorithm and Concomitant Biomarker Identification for NSCLC Prediction Using Multi-Omics Data Integration.

Early diagnosis of lung cancer to increase the survival rate, which is currently at a low range of mid-30%, remains a critical need. Despite this, multi-omics data have rarely been applied to non-small-cell lung cancer (NSCLC) diagnosis. We developed a multi-omics data-affinitive artificial intelligence algorithm based on the graph convolutional network that integrates mRNA expression, DNA methylation, and DNA sequencing data. This NSCLC prediction model achieved a 93.7% macro F1-score, indicating that values for false positives and negatives were substantially low, which is desirable for accurate classification. Gene ontology enrichment and pathway analysis of features revealed that two major subtypes of NSCLC, lung adenocarcinoma and lung squamous cell carcinoma, have both specific and common GO biological processes. Numerous biomarkers (i.e., microRNA, long non-coding RNA, differentially methylated regions) were newly identified, whereas some biomarkers were consistent with previous findings in NSCLC (e.g., SPRR1B). Thus, using multi-omics data integration, we developed a promising cancer prediction algorithm.

Investigation of the Effect of 3D Meniscus Geometry on Fluid Dynamics and Crystallization via In Situ Optical Microscopy-Assisted Mathematical Modeling.

Solution-based thin-film solidification is a complex process involving various transport phenomena that are intricately dependent on multiple experimental parameters. The difficulty of analyzing this process experimentally or conducting exact numerical simulation make it challenging to understand, predict, and control the solidification process. In this work, a simple and effective technique to analyze the thin-film solidification process during solution shearing, based on 3D geometrical model of the meniscus, is proposed. The 3D meniscus geometry, which changes depending on the experimental parameters, is attained using high-speed side-view and top-view in situ microscopy. Thereafter, mass and momentum transport mathematical models are applied to obtain numerical solutions of transport phenomena within the meniscus. Utilizing these results, the underlying mechanism of dendritic growth of small molecule organic semiconductor is elucidated, which has previously been unknown. The 3D meniscus modeling is particularly important for this analysis, as dendrite formation is strongly dependent on the meniscus geometry near the contact line and mass transport variation perpendicular to the coating direction. This technique enables the study of complex relationship between experimental parameters and solidification process, which is widely applicable to various materials and coating systems; whereby, better understanding of thin-film growth and device performance optimization is possible.

Computational Method-Based Optimization of Carbon Nanotube Thin-Film Immunosensor for Rapid Detection of SARS-CoV-2 Virus.

The recent global spread of COVID-19 stresses the importance of developing diagnostic testing that is rapid and does not require specialized laboratories. In this regard, nanomaterial thin-film-based immunosensors fabricated via solution processing are promising, potentially due to their mass manufacturability, on-site detection, and high sensitivity that enable direct detection of virus without the need for molecular amplification. However, thus far, thin-film-based biosensors have been fabricated without properly analyzing how the thin-film properties are correlated with the biosensor performance, limiting the understanding of property-performance relationships and the optimization process. Herein, the correlations between various thin-film properties and the sensitivity of carbon nanotube thin-film-based immunosensors are systematically analyzed, through which optimal sensitivity is attained. Sensitivities toward SARS-CoV-2 nucleocapsid protein in buffer solution and in the lysed virus are 0.024 [fg/mL]-1 and 0.048 [copies/mL]-1, respectively, which are sufficient for diagnosing patients in the early stages of COVID-19. The technique, therefore, can potentially elucidate complex relationships between properties and performance of biosensors, thereby enabling systematic optimization to further advance the applicability of biosensors for accurate and rapid point-of-care (POC) diagnosis.

Microfluidic Screening-Assisted Machine Learning to Investigate Vertical Phase Separation of Small Molecule:Polymer Blend.

Solution-based thin-film processing is a widely utilized technique for the fabrication of various devices. In particular, the tunability of the ink composition and coating condition allows precise control of thin-film properties and device performance. Despite the advantage of having such tunability, the sheer number of possible combinations of experimental parameters render it infeasible to efficiently optimize device performance and analyze the correlation between experimental parameters and device performance. In this work, a microfluidic screening-embedded thin-film processing technique is developed, through which thin-films of varying ratios of small molecule semiconductor:polymer blend are simultaneously generated and screened in a time- and resource-efficient manner. Moreover, utilizing the thin-films of varying combinations of experimental parameters, machine learning models are trained to predict the transistor performance. Gaussian Process Regression (GPR) algorithms tuned by Bayesian optimization shows the best predictive accuracy amongst the trained models, which enables narrowing down of the combinations of experimental parameters and investigation of the degree of vertical phase separation under the predicted parameter space. The technique can serve as a guideline for elucidating the underlying complex parameter-property-performance correlations in solution-based thin-film processing, thereby accelerating the optimization of various thin-film devices in the future.

Polyvinylidene fluoride/silk fibroin-based bio-piezoelectric nanofibrous scaffolds for biomedical application.

Since the discovery that applying electrical stimulation can promote cell growth, proliferation, and tissue regeneration, research on bio-piezoelectric materials is being actively conducted. In this study, a composite material was prepared by mixing polyvinylidene fluoride (PVDF), a conventional piezoelectric polymer, and silk fibroin (SF), a natural piezoelectric material that recently attracting attention. These two polymers were fabricated into a composite fiber mat using electrospinning technology. To find optimal conditions, SF was added in various ratios to prepare electrospun PVDF/SF mats. The characteristics of these PVDF/SF composite mats were then analyzed through various evaluations and in vitro studies. It was confirmed that PVDF and SF were successfully mixed through scanning electron microscope images and structural analysis such as x-ray diffractometer and Fourier transform infrared. The results revealed that adding an appropriate amount of SF could improve the tensile strength, enhance cell proliferation rate, and generate a voltage similar to that of a conventional PVDF-only electrospinning mat. Such fabricated electrospun PVDF/SF composite mats are expected to be useful in the bio-piezoelectric field because they can maintain piezoelectricity while compensating for the shortcomings, such as low physical properties, of a PVDF electrospun mat.

Alu cell-free DNA concentration, Alu index, and LINE-1 hypomethylation as a cancer predictor.

INTRODUCTION: The liquid biopsy approach, a less-invasive diagnostic tool, enables the detection of disease-specific genetic and epigenetic aberrations. Approximately 66-69% of the human genome may be composed of transposable repetitive elements, including Alu and LINE-1. This study aimed to investigate whether Alu-derived cell-free DNA (cfDNA) concentrations, Alu index, and LINE-1 methylation could be used to distinguish patients with cancers from healthy individuals. METHODS: Two sets of primers, shorter and longer Alu fragments, were used to amplify Alu elements, followed by the quantitation of Alu DNA concentration and its integrity index. LINE-1 methylation status was then analyzed with quantitative PCR using methylation- and unmethylation-specific TaqMan probes. RESULTS: Both Alu index and LINE-1 methylation level were significantly different in comparison between patients with lung or breast cancer and the healthy controls. The area under the ROC curve of the Alu index and LINE-1 hypomethylation was 0.742 and 0.848 for lung cancer, respectively, and 0.724 and 0.890 for breast cancer, respectively. However, Alu longer fragment DNA concentration was significantly correlated with Alu index in comparison to LINE-1 hypomethylation. Regression analysis suggested that the LINE-1 methylation level, rather than the Alu index, was a good discriminator for lung and breast cancers. CONCLUSIONS: This study investigated the genome-wide Alu index and LINE-1 methylation status; their associations with cancers suggested that these combinatory panels could be implemented as a triage test to discriminate cancer patients from healthy individuals.

Simple conversion of 3D electrospun nanofibrous cellulose acetate into a mechanically robust nanocomposite cellulose/calcium scaffold.

Cellulose and its derivatives are widely used as nanofibrous biomaterials, but obtaining 3D cellulose nanofibers is difficult and relevant research is scarce. In the present study, we propose a simple method for converting electrospun 3D cellulose acetate/lactic acid nanofibers via calcium hydroxide treatment into a 3D cellulose/calcium lactate nanocomposite matrix. The conversion resulted in producing a stronger nanofibrous matrix (1.382 MPa vs. 0.112 MPa) that is more hydrophilic and cell-friendly compared to the untreated cellulose acetate/lactic acid group. The successful conversion was verified via FTIR, XPS, TGA, DTG, and XRD. The ability of the scaffolds to provide a suitable environment for cell growth and infiltration was verified by CCK assay and confocal microscopy. The porous nature, mechanical strength, and presence of calcium make the 3D cellulose/calcium lactate matrix a promising material for bone tissue engineering.

Numerical Simulations and In Situ Optical Microscopy Connecting Flow Pattern, Crystallization, and Thin-Film Properties for Organic Transistors with Superior Device-to-Device Uniformity.

Currently, due to the lack of precise control of flow behavior and the understanding of how it influences thin-film crystallization, strict tuning of thin-film properties during solution-based coating is difficult. In this work, a continuous-flow microfluidic-channel-based meniscus-guided coating (CoMiC) is introduced, which is a system that enables manipulation of flow patterns and analysis connecting flow pattern, crystallization, and thin-film properties. Continuous supply of a solution of an organic semiconductor with various flow patterns is generated using microfluidic channels. 3D numerical simulations and in situ microscopy allow the tracking of the flow pattern along its entire path (from within the microfluidic channel to near the liquid-solid boundary), and enable direct observation of thin-film crystallization process. In particular, the generation of chaotic flow results in unprecedented device-to-device uniformity, with coefficient of variation (CV) of 7.3% and average mobility of 2.04 cm2 V-1 s-1 in doped TIPS-pentacene. Furthermore, CV and average mobility of 9.6% and 11.4 cm2 V-1 s-1 are achieved, respectively, in a small molecule:polymer blend system. CoMiC can serve as a guideline for elucidating the relation between flow behavior, liquid-to-solid phase transition, and device performance, which has thus far been unknown.

Effects of fermented rice bran on DEN-induced oxidative stress in mice: GSTP1, LINE-1 methylation, and telomere length ratio.

N-diethylnitrosamine (DEN), a well-known carcinogen, not only induces excessive reactive oxygen species but also suppresses DNA methylation. This study investigated the effect of fermented rice bran (FRB) treatment on DEN-induced oxidative stress through DNA methylation and telomere length analysis. To evaluate the potential protective role of FRB in oxidative stress, two different doses of FRB, DEN, and their combination were administered to mice that were preadapted or not to FRB. Glutathione-S-transferase P1 (GSTP1) methylation levels significantly decreased at 2 and 24 hr after FRB and DEN co-administration in mice with and without pre-adaptation. Moreover, GSTP1 mRNA was upregulated under DEN-induced oxidative stress. Furthermore, changes in long interspersed nuclear element-1 methylation were observed from the viewpoint of genomic instability. In addition, FRB preadapted mice displayed a lower telomere length ratio than the non-adapted mice, suggesting that FRB adaptation offers advantages over the non-adapted conditions in terms of inflammation suppression. PRACTICAL APPLICATIONS: DEN induces excessive ROS, which is associated with oxidative stress on DNA and other cellular components, resulting in inflammation. This study shows that FRB may alleviate DEN-triggered oxidative stress, based on changes in GSTP1, LINE-1 methylation, and telomere length ratios, thereby, revealing the potential of dietary intervention during inflammation. Furthermore, this study furthers the current understanding of DNA methylation mechanisms underlying the antioxidant and anti-inflammatory effects of functional food components. These results indicate that dietary inclusion of FRB may help decrease oxidative DNA damage and its associated inflammation at early stages of a disease.

In Situ Biological Transmutation of Catalytic Lactic Acid Waste into Calcium Lactate in a Readily Processable Three-Dimensional Fibrillar Structure for Bone Tissue Engineering.

A bioinspired three-dimensional (3D) fibrous structure possesses biomimicry, valuable functionality, and performance to scaffolding in tissue engineering. In particular, an electrospun fibrous mesh has been studied as a scaffold material in various tissue regeneration applications. We produced a low-density 3D polycaprolactone/lactic acid (LA) fibrous mesh (3D-PCLS) via the novel lactic-assisted 3D electrospinning technique exploiting the catalytic properties of LA as we reported previously. In the study, we demonstrated a strategy of recycling the LA component to synthesize the osteoinductive biomolecules in situ, calcium lactate (CaL), thereby forming a 3D bioactive PCL/CaL fibrous scaffold (3D-SCaL) for bone tissue engineering. The fiber morphology of 3D-PCLS and its packing degree could have been tailored by modifying the spinning solution and the collector design. 3D-SCaL demonstrated successful conversion of CaL from LA and exhibited the significantly enhanced biomineralization capacity, cell infiltration and proliferation rate, and osteoblastic differentiation in vitro with two different cell lines, MC3T3-e1 and bone marrow stem cells. In conclusion, 3D-SCaL proves to be a highly practical and accessible strategy using a variety of polymers to produce 3D fibers as a potential candidate for future regenerative medicine and tissue engineering applications.

Effective Schottky barrier lowering of NiGe/p-Ge(100) using Terbium interlayer structure for high performance p-type MOSFETs.

Ultra-low contact resistance at the interface between NiGe and p-Ge, i.e., NiGe/p-Ge was achieved by introducing terbium (Tb) as an interlayer in forming NiGe using Tb/Ni/TiN structure. The contact resistance value obtained using the circular transmission line model for an 8-nm thick Tb interlayer sample was 7.21 × 10-8 Ω·cm2, which is two orders of magnitude less than that of reference sample (without the Tb interlayer) of 7.36 × 10-6 Ω·cm2. The current-voltage characteristics were studied at a temperature range of -110 ~ 25 °C to determine the effective Schottky barrier height (eSBH). An eSBH of 0.016 eV was obtained for the 8-nm thick Tb interlayer. Various Tb interlayer thicknesses were selected to study their effect on the contact resistance. The Tb interlayer surface and structural properties were characterized using FESEM, XRD, XPS, TEM, and SIMS analyses.

Fabrication of 3D Electrospun Polycaprolactone Sponge Incorporated with Pt@AuNPs for Biomedical Applications.

Here, we report the synthesis of three-dimensional (3D) polycaprolactone (PCL) nanofiber incorporated with core-satellite platinum nanoparticles (PtNPs, 2-3 nm) coated gold nanospheres (AuNPs, 30 nm) via the simple lactic acid assisted self-assembly electrospinning technique. The Pt-AuNPs nanoparticle in core-satellite form has been prepared by following solution based methods and characterized with TEM, HR-TEM, UV-Visible, and XRD spectroscopic techniques. The surface morphology and structural analysis of 3D nanofiber scaffolds have been performed with FTIR, TGA, FESEM, and HR-TEM analysis techniques and shown the successful preparation of 3D electrospun fibrous structure composed of Pt-AuNPs loaded PCL (PCL@Pt-AuNPs) as a potential biomaterial for bone tissue engineering applications.

Versatile Processing of Metal-Organic Framework-Fluoropolymer Composite Inks with Chemical Resistance and Sensor Applications.

We report a new class of metal-organic framework (MOF) inks with a water-repellent, photocurable fluoropolymer (PFPE) having up to 90 wt % MOF loading. These MOF inks are enabled to process various MOFs through spray coating, pen writing, stencil printing, and molding at room temperature. Upon UV curing, the hydrophobic PFPE matrix efficiently blocks water permeation but allows accessibility of chemicals into the MOF pores, thereby freeing the MOF to perform its unique function. Moreover, by introducing functional MOFs we successfully demonstrated a water-tolerant chemosensor for a class of aromatic pollutants in water and a chemical-resistant thermosensor for visualizing temperature image. This approach would open up innumerable opportunities for those MOFs that are otherwise dormant.

NLRP1 and NTN1, Deregulated Blood Differentially Methylated Regions in Mild Cognitive Impairment Patients.

Epigenetic dysregulation has been known to be involved in neurodegenerative diseases, including amnestic mild cognitive impairment (MCI). The aim of this study was to investigate the genome-wide DNA methylation analysis, in order to identify epigenetic dysregulation in blood from patients with MCI. Here, we investigated whether epigenetic dysregulation in MCI and whether such an aberration could be detected in blood circulation. Genome-wide bisulfite sequencing targeted 84 million bases covering 3.7 million CpG sites was comparatively analyzed in MCI and control groups. And correlation between DNA methylation and transcriptomic changes was sought. Significant differentially methylated regions (DMRs) distinguishing the MCI and control groups were identified and functionally annotated. Most DMRs specific to MCI were enriched between - 2 kb and + 2 kb of the CpG island start sites located within or near gene promoters. Representative hypo- and hypermethylated DMRs in MCI were confirmed to be correlated to mRNA expression changes with the comparative delta Ct method. DNA methylation aberrations involving metal ion homeostasis, axon growth, inflammasome, and others in this study may be less-invasive, easily measurable blood biomarker candidates for MCI.

Inorganic Polymer Micropillar-Based Solution Shearing of Large-Area Organic Semiconductor Thin Films with Pillar-Size-Dependent Crystal Size.

It is demonstrated that the crystal size of small-molecule organic semiconductors can be controlled during solution shearing by tuning the shape and dimensions of the micropillars on the blade. Increasing the size and spacing of the rectangular pillars increases the crystal size, resulting in higher thin-film mobility. This phenomenon is attributed as the microstructure changing the degree and density of the meniscus line curvature, thereby controlling the nucleation process. The use of allylhybridpolycarbosilane (AHPCS), an inorganic polymer, is also demonstrated as the microstructured blade for solution shearing, which has high resistance to organic solvents, can easily be microstructured via molding, and is flexible and durable. Finally, it is shown that solution shearing can be performed on a curved surface using a curved blade. These demonstrations bring solution shearing closer to industrial applications and expand its applicability to various printed flexible electronics.