Periodic magnetic modulation enhanced electrochemical analysis for highly sensitive determination of genomic DNA methylation.

DNA methylation aberrations have a strong correlation with cancer in early detection, diagnosis, and prognosis, which make them possible candidate biomarkers. Electrochemical biosensors offer rapid protocols for detecting DNA methylation status with minimal pretreatment of samples. However, the inevitable presence of background current in the time domain, including electrochemical noise and variations, limits the detection performance of these biosensors, especially for low concentration analytes. Here, we propose an ultrasensitive frequency-domain electrochemical analysis strategy to effectively separate the weak signals from background current. To achieve this, we employed periodic magnetic field modulation of magnetic beads (MBs) on and off the electrode surface to generate a periodic electrochemical signal for subsequent frequency-domain analysis. By capturing labeled MBs with as low as 0.5 pg of DNA, we successfully demonstrated a highly sensitive electrochemical method for determination of genome-wide DNA methylation levels. We also validated the effectiveness of this methodology using DNA samples extracted from three types of hepatocellular carcinoma (HCC) cell lines. The results revealed varying genomic methylation levels among different HCC cell lines, indicating the potential application of this approach for early-stage cancer detection in terms of DNA methylation status.

Lasing in Zn-doped GaAs nanowires on an iron film.

In this work, we demonstrate optically pumped lasing in highly Zn-doped GaAs nanowires (NWs) lying on an iron film. The conically shaped NWs are first covered with an 8 nm thick Al2O3film to prevent atmospheric oxidation and mitigate band-bending effects. Multimode and single-mode lasing have been observed for NWs with a length greater or smaller than 2µm, respectively. Finite difference time domain calculations reveal a weak electric field enhancement in the Al2O3layer at the NW/iron film interface for the lasing modes. The high Zn acceptor concentration in the NWs provides enhanced radiative efficiency and enables lasing on the iron film despite plasmonic losses. Our results open avenues for integrating NW lasers on ferromagnetic substrates to achieve new functionalities, such as magnetic field-induced modulation.

Redox-Regulated Magnetic Conversions between Ferro- and Antiferromagnetism in Organic Nitroxide Diradicals.

Redox-induced magnetic transformation in organic diradicals is an appealing phenomenon. In this study, we theoretically designed twelve couples of diradicals in which two nitroxide (NO) radical groups are connected to the redox-active couplers including p-benzoquinonyl, 1,4-naphthoquinyl, 9,10-anthraquinonyl, naphthacene-5,12-dione, pentacene-6,13-dione, hexacene-6,15-dione, pyrazinyl, quinoxalinyl, phenazinyl, 5,12-diazanaphthacene, 6,13-diazapentacene, and 6,15-diazahexacene. As evidenced at both the B3LYP and M06-2X levels of theory, the calculations reveal that the magnetic reversal can take place from ferromagnetism to antiferromagnetism, or vice versa, by means of redox method in these designed organic magnetic molecules. It was observed that p-benzoquinonyl, 1,4-naphthoquinyl, 9,10-anthraquinonyl, naphthacene-5,12-dione, pentacene-6,13-dione, and hexacene-6,15-dione-bridged NO diradicals produce antiferromagnetism while their dihydrogenated counterparts exhibit ferromagnetism. Similarly, pyrazinyl, quinoxalinyl, phenazinyl, 5,12-diazanaphthacene, 6,13-diazapentacene, and 6,15-diazahexacene-bridged NO diradicals present ferromagnetism while their dihydrogenated counterparts show antiferromagnetism. The differences in the magnetic behaviors and magnetic magnitudes of each of the twelve couples of diradicals could be attributed to their distinctly different spin-interacting pathways. It was found that the nature of the coupler and the length of the coupling path are important factors in controlling the magnitude of the magnetic exchange coupling constant J. Specifically, smaller HOMO-LUMO (HOMO: highest occupied molecular orbital, LUMO: lowest unoccupied molecular orbital) gaps of the couplers and shorter coupler lengths, as well as shorter linking bond lengths, can attain stronger magnetic interactions. In addition, a diradical with an extensively π-conjugated structure is beneficial to spin transport and can effectively promote magnetic coupling, yielding a large |J| accordingly. That is, a larger spin polarization can give rise to a stronger magnetic interaction. The sign of J for these studied diradicals can be predicted from the spin alternation rule, the shape of the singly occupied molecular orbitals (SOMOs), and the SOMO-SOMO energy gaps of the triplet state. This study paves the way for the rational design of magnetic molecular switches.

Multiple Bioimaging Applications Based on the Excellent Properties of Nanodiamond: A Review.

Nanodiamonds (NDs) are emerging as a promising candidate for multimodal bioimaging on account of their optical and spectroscopic properties. NDs are extensively utilized for bioimaging probes due to their defects and admixtures in their crystal lattice. There are many optically active defects presented in NDs called color centers, which are highly photostable, extremely sensitive to bioimaging, and capable of electron leap in the forbidden band; further, they absorb or emit light when leaping, enabling the nanodiamond to fluoresce. Fluorescent imaging plays a significant role in bioscience research, but traditional fluorescent dyes have some drawbacks in physical, optical and toxicity aspects. As a novel fluorescent labeling tool, NDs have become the focus of research in the field of biomarkers in recent years because of their various irreplaceable advantages. This review primarily focuses on the recent application progress of nanodiamonds in the field of bioimaging. In this paper, we will summarize the progress of ND research from the following aspects (including fluorescence imaging, Raman imaging, X-ray imaging, magnetic modulation fluorescence imaging, magnetic resonance imaging, cathodoluminescence imaging, and optical coherence tomography imaging) and expect to supply an outlook contribution for future nanodiamond exploration in bioimaging.

Magnetic Interacted Interaction Effect in MXene Skeleton: Enhanced Thermal-Generation for Electromagnetic Interference Shielding.

With the rapid advancements of portable and wearable equipment, high-efficiency electromagnetic interference (EMI) shielding materials are highly entailed to eliminate radiated electromagnetic pollution. Herein, by assembling hexagonal SrFe12 O19 flakes into a Ti3 C2 Tx MXene/MWCNT substrate, a magnetized Ti3 C2 Tx -based film is successfully fabricated by a facile filtration approach. Carbon nanotubes are used as isolation agents to realize the submicroscopic dispersion of MXene and SrFe12 O19 . The obtained MXene/MWCNTs/SrFe12 O19 film shows a high electrical conductivity of 438 S cm-1 and an excellent EMI shielding effectiveness of 62.9 dB in X-band at a thickness of only 40 µm. Benefiting from a strong magnetic response ability and an expanded magnetic coupling space, hexagonal SrFe12 O19 sheets can efficiently consume incident magnetic field energy by domain wall migration and the ferromagnetic resonance effect. Boosted EMI shielding performance can be achieved by improving the magnetic loss in the Ti3 C2 Tx MXene/MWCNTs/SrFe12 O19 film, preventing the secondary reflection of electromagnetic waves. Meanwhile, magnetized MXene-based films display the freestanding and flexible features and are suitable for installation in electric devices. It is anticipated that this strategy offers new ideas for designing EMI shielding films and in broadening potential utility of MXene-based materials.

Recent Advances in Rapid and Highly Sensitive Detection of Proteins and Specific DNA Sequences Using a Magnetic Modulation Biosensing System.

In early disease stages, biomolecules of interest exist in very low concentrations, presenting a significant challenge for analytical devices and methods. Here, we provide a comprehensive overview of an innovative optical biosensing technology, termed magnetic modulation biosensing (MMB), its biomedical applications, and its ongoing development. In MMB, magnetic beads are attached to fluorescently labeled target molecules. A controlled magnetic force aggregates the magnetic beads and transports them in and out of an excitation laser beam, generating a periodic fluorescent signal that is detected and demodulated. MMB applications include rapid and highly sensitive detection of specific nucleic acid sequences, antibodies, proteins, and protein interactions. Compared with other established analytical methodologies, MMB provides improved sensitivity, shorter processing time, and simpler protocols.

MNP-Enhanced Microwave Medical Imaging by Means of Pseudo-Noise Sensing.

Magnetic nanoparticles have been investigated for microwave imaging over the last decade. The use of functionalized magnetic nanoparticles, which are able to accumulate selectively within tumorous tissue, can increase the diagnostic reliability. This paper deals with the detecting and imaging of magnetic nanoparticles by means of ultra-wideband microwave sensing via pseudo-noise technology. The investigations were based on phantom measurements. In the first experiment, we analyzed the detectability of magnetic nanoparticles depending on the magnetic field intensity of the polarizing magnetic field, as well as the viscosity of the target and the surrounding medium in which the particles were embedded, respectively. The results show a nonlinear behavior of the magnetic nanoparticle response depending on the magnetic field intensity for magnetic nanoparticles diluted in distilled water and for magnetic nanoparticles embedded in a solid medium. Furthermore, the maximum amplitude of the magnetic nanoparticles responses varies for the different surrounding materials of the magnetic nanoparticles. In the second experiment, we investigated the influence of the target position on the three-dimensional imaging of the magnetic nanoparticles in a realistic measurement setup for breast cancer imaging. The results show that the magnetic nanoparticles can be detected successfully. However, the intensity of the particles in the image depends on its position due to the path-dependent attenuation, the inhomogeneous microwave illumination of the breast, and the inhomogeneity of the magnetic field. Regarding the last point, we present an approach to compensate for the inhomogeneity of the magnetic field by computing a position-dependent correction factor based on the measured magnetic field intensity and the magnetic susceptibility of the magnetic particles. Moreover, the results indicate an influence of the polarizing magnetic field on the measured ultra-wideband signals even without magnetic nanoparticles. Such a disturbing influence of the polarizing magnetic field on the measurements should be reduced for a robust magnetic nanoparticles detection. Therefore, we analyzed the two-state (ON/OFF) and the sinusoidal modulation of the external magnetic field concerning the detectability of the magnetic nanoparticles with respect to these spurious effects, as well as their practical application.

Highly Sensitive and Specific Zika Virus Serological Assays Using a Magnetic Modulation Biosensing System.

BACKGROUND: Zika virus has created global alarm because it has been associated with catastrophic fetal abnormalities, including microcephaly, spontaneous abortion, and intrauterine growth restriction. Current serological assays that detect antiviral antibodies suffer from low sensitivity and high cross-reactivity among different flaviviruses. METHODS: In this study, utilizing a novel magnetic modulation biosensing (MMB) system and the Zika nonstructural 1 protein, we show highly sensitive and specific Zika serological assays. We blindly tested 60 reverse-transcription polymerase chain reaction Zika-positive samples and healthy patients' serum samples, as well as 44 serum samples from enzyme-linked immunosorbent assay (ELISA) West Nile- and dengue-positive patients. The Zika-positive samples were collected from Israeli travelers returning from Zika-endemic areas. RESULTS: The MMB Zika assays have 88%-97% sensitivity, much higher than the current state-of-the-art EUROIMMUN ELISA assays (38%-74%). In addition, the specificity is 100%, and the cross-reactivity with West Nile and dengue viruses is minimal (0%-4%). Furthermore, the MMB assays detected Zika IgM antibodies as early as 5 days and as late as 180 days postsymptoms onset, significantly extending the number of days that the antibodies are detectable. CONCLUSIONS: The sensitivity, specificity, and simplicity of the MMB assays may significantly improve Zika diagnosis and provide accurate results for public health agencies.

Improving the Sensitivity of Fluorescence-Based Immunoassays by Photobleaching the Autofluorescence of Magnetic Beads.

In fluorescence-based assays, usually a target molecule is captured using a probe conjugated to a capture surface, and then detected using a second fluorescently labeled probe. One of the most common capture surfaces is a magnetic bead. However, magnetic beads exhibit strong autofluorescence, which often overlaps with the emission of the reporter fluorescent dyes and limits the analytical performance of the assay. Here, several widely used magnetic beads are photobleached and their autofluorescence is reduced to 1% of the initial value. Their autofluorescence properties, including their photobleaching decay rates and autofluorescence spectra pre- and post-photobleaching, and the stability of the photobleaching over a period of two months are analyzed. The photobleached beads are stable over time and their surface functionality is retained. In a high-sensitivity LX-200 system using photobleached magnetic beads, human interleukin-8 is detected with a threefold improvement in detection limit and signal-to-noise ratio over results achievable with nonbleached beads. Since many contemporary immunoassays rely on magnetic beads as capture surfaces, prebleaching the beads may significantly improve the analytical performance of these assays. Moreover, nonmagnetic beads with low autofluorescence are also successfully photobleached, suggesting that photobleaching can be applied to various capture surfaces used in fluorescence-based assays.

Magnetic modulation of lysosomes for cancer therapy.

Lysosomes play a central role in biochemical signal transduction and oxidative stress in cells. Inducing lysosome membrane penetration (LMP) to cause lysosomal-dependent cell death (LCD) in tumor cells is an effective strategy for cancer therapy. Chemical drugs can destroy the stability of lysosomes by neutralizing protons within the lysosomes or enhancing the fragility of the lysosomal membranes. However, there remain several unsolved problems of traditional drugs in LMP induction due to insufficient lysosomal targeting, fast metabolism, and toxicity in normal cells. With the development of nanotechnology, magnetic nanoparticles have been demonstrated to target lysosomes naturally, providing a versatile tool for lysosomal modulation. Combined with excellent tissue penetration and spatiotemporal manipulability of magnetic fields, magnetic modulation of lysosomes progresses rapidly in inducing LMP and LCD for cancer therapy. This review comprehensively discussed the strategies of magnetic modulation of lysosomes for cancer therapy. The intrinsic mechanisms of LMP-induced LCD were first introduced. Then, the modulation of lysosomes by diverse physical outputs of magnetic fields was emphatically discussed. Looking forward, this review will shed the light on the prospect of magnetic modulation of lysosomes, inspiring future research of magnetic modulation strategy in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Stimulation of vagus nerve for patients with disorders of consciousness: a systematic review.

Purpose: The purpose of this study is to evaluate the efficacy and safety of stimulating the vagus nerve in patients with disorders of consciousness (DOCs). Methods: A comprehensive systematic review was conducted, encompassing the search of databases such as PubMed, CENTRAL, EMBASE and PEDro from their inception until July 2023. Additionally, manual searches and exploration of grey literature were performed. The literature review was conducted independently by two reviewers for search strategy, selection of studies, data extraction, and judgment of evidence quality according to the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) Study Quality Scale. Results: A total of 1,269 articles were retrieved, and 10 studies met the inclusion criteria. Among these, there were three case reports, five case series, and only two randomized controlled trials (RCTs). Preliminary studies have suggested that stimulation of vagus nerve can enhance the levels of DOCs in both vegetative state/unresponsive wakefulness state (VS/UWS) and minimally conscious state (MCS). However, due to a lack of high-quality RCTs research and evidence-based medical evidence, no definitive conclusion can be drawn regarding the intervention's effectiveness on consciousness level. Additionally, there were no significant adverse effects observed following stimulation of vagus nerve. Conclusion: A definitive conclusion cannot be drawn from this systematic review as there was a limited number of eligible studies and low-quality evidence. The findings of this systematic review can serve as a roadmap for future research on the use of stimulation of vagus nerve to facilitate recovery from DOCs.

Magnetic-Responsive Surface-Enhanced Raman Scattering Platform with Tunable Hot Spot for Ultrasensitive Virus Nucleic Acid Detection.

Surface-enhanced Raman scattering (SERS)-based biosensors are promising tools for virus nucleic acid detection. However, it remains challenging for SERS-based biosensors using a sandwiching strategy to detect long-chain nucleic acids such as nucleocapsid (N) gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because the extension of the coupling distance (CD) between the two tethered metallic nanostructures weakens electric field and SERS signals. Herein, we report a magnetic-responsive substrate consisting of heteoronanostructures that controls the CD for ultrasensitive and highly selective detection of the N gene of SARS-CoV-2. Significantly, our findings show that this platform reversibly shortens the CD and enhances SERS signals with a 10-fold increase in the detection limit from 1 fM to 100 aM, compared to those without magnetic modulation. The optical simulation that emulates the CD shortening process confirms the CD-dependent electric field strength and further supports the experimental results. Our study provides new insights into designing a stimuli-responsive SERS-based platform with tunable hot spots for long-chain nucleic acid detection.

Magnetic modulation of core@shell MoS2-based flower-like multicomponent nanocomposites to improve microwave attenuation.

Nanocomposites with a three-dimensional (3D) flower-like geometrical morphology were considered as excellent microwave absorbers (MAs) because of the numerous effective sites for the multiple reflections of electromagnetic (EM) wave. Herein, for optimizing the EM matching characteristic and taking full advantage of interface polarization, a strategy of magnetic modulation was proposed to further improve the EM wave absorption performances (EMWAPs) of MoS2-based nanocomposites. We adopted a simple hydrothermal route and a combined method of hydrothermal treatment/hydrogen reduction to synthesize core@shell CoFe2O4@MoS2 and CoFe@MoO2/MoS2 flower-like nanocomposites, respectively. The obtained results indicated that the hydrogen reduction effectively improved their magnetic properties and magnetic loss capabilities, and their 3D flower-like geometrical morphologies were well maintained during the hydrogen reduction process. The obtained core@shell CoFe@MoO2/MoS2 flower-like nanocomposites presented the extraordinary comprehensive EMWAPs including the optimal reflection loss value of -54.83 dB with the matching thicknesses (dm) value of 2.05 mm and effective absorption bandwidth value of 6.40 GHz with the dm value of 2.59 mm, which were evidently superior to the properties of CoFe2O4@MoS2. Therefore, the findings provided an effective pathway to further improve EMWAPs of MoS2-based core@shell nanocomposites and the as-prepared core@shell CoFe@MoO2/MoS2 flower-like nanocomposites could be utilized as the novel high-efficient MAs.

Rapid Biosensing Method for Detecting Protein-DNA Interactions.

Identifying and investigating protein-DNA interactions, which play significant roles in many biological processes, is essential for basic and clinical research. Current techniques for identification of protein-DNA interactions are laborious, time-consuming, and suffer from nonspecific binding and limited sensitivity. To overcome these challenges and assess protein-DNA interactions, we use a magnetic modulation biosensing (MMB) system. In MMB, one of the interacting elements (protein or DNA) is immobilized to magnetic beads, and the other is coupled to a fluorescent molecule. Thus, the link between the magnetic bead and the fluorescent molecule is established only when binding occurs, enabling detection of the protein-DNA interaction. Using magnetic forces, the beads are concentrated and manipulated in a periodic motion in and out of a laser beam, producing a detectable oscillating signal. Using MMB, we detected protein-DNA interactions between short GC-rich DNA sequences and both a purified specificity protein 1 (Sp1) and an overexpressed Buttonhead (BTD) protein in a cell lysate. The specificity of the interactions was assessed using mutated DNA sequences and competition experiments. The assays were experimentally compared with commonly used electrophoretic mobility shift assay, which takes approximately 4-72 h. In comparison, the MMB-based assay's turnaround time is ∼2 h, and it provides unambiguous results and quantitative measures of performance. The MMB system uses simple and cheap components, making it an attractive alternative method over current costly and time-consuming techniques for analyzing protein-DNA interactions. Therefore, we anticipate that the MMB-based technique will significantly advance the detection of protein-DNA interactions in biomedical research.

Magnetic Control of Optical Reflectance from Metallic Thin Film Using Surface Plasmon Resonance and Faraday Rotation.

We demonstrate magnetic control of optical reflectance with no ferromagnetic material via combining the Faraday rotation and the surface plasmon resonance (SPR) in a Kretschman configuration under magnetic fields < 0.5 T. The SPR produces the polarization sensitive reflectance from the Au or Ag thin film coated on a N-BK7 prism in which the Faraday rotation occurs. The gold (Au) or silver (Ag) metal film as a plasmonic film somewhat acts as an incident angle-dependent reflection polarizer that can sensitively sense the polarization change induced by the Faraday rotation that occurs in a prism. We find that combination of Faraday rotation and the surface plasmon can induce a significant magnetic modulation of reflectance normalized with respect to that obtained with no magnetic fields at a specific incident angle of light. The magnetic control of optical reflectance presented may find an application in polarizer-free photonic devices with no ferromagnetic material for magneto-optical modulation.

Highly Sensitive and Specific SARS-CoV-2 Serological Assay Using a Magnetic Modulation Biosensing System.

Sensitive serological assays are needed to provide valuable information about acute and past viral infections. For example, detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies could serve as the basis for an "immunity passport" that would enable individuals to travel internationally. Here, utilizing a novel Magnetic Modulation Biosensing (MMB) system and the receptor-binding domain of the SARS-CoV-2 spike protein, we demonstrate a highly sensitive and specific anti-SARS-CoV-2 IgG serological assay. Using anti-SARS-CoV-2 IgG antibodies, RT-qPCR SARS-CoV-2-positive and healthy patients' samples, and vaccinees' samples, we compare the MMB-based SARS-CoV-2 IgG assay's analytical and clinical sensitivities to those of the enzyme-linked immunosorbent assay (ELISA). Compared with ELISA, the MMB-based assay has an ~6-fold lower limit of detection (129 ng/L vs. 817 ng/L), and it detects an increase in the IgG concentration much earlier after vaccination. Using 85 RT-qPCR SARS-CoV-2-positive samples and 79 -negative samples, the MMB-based assay demonstrated similar clinical specificity (98% vs. 99%) and sensitivity (93% vs. 92%) to the ELISA test, but with a much faster turnaround time (45 min vs. 245 min). The high analytical and clinical sensitivity, short turnaround time, and simplicity of the MMB-based assay makes it a preferred method for antibody detection.

Nanodiamond-enabled biomedical imaging.

Biomedical imaging allows in vivo studies of organisms, providing valuable information of biological processes at both cellular and tissue levels. Nanodiamonds have recently emerged as a new type of probe for fluorescence imaging and contrast agent for magnetic resonance and photoacoustic imaging. Composed of sp3-carbon atoms, diamond is chemically inert and inherently biocompatible. Uniquely, its matrix can host a variety of optically and magnetically active defects suited for bioimaging applications. Since the first production of fluorescent nanodiamonds in 2005, a large number of experiments have demonstrated that fluorescent nanodiamonds are useful as photostable markers and nanoscale sensors in living cells and organisms. In this review, we focus our discussion on the recent advancements of nanodiamond-enabled biomedical imaging for preclinical applications.

Quantification and Imaging of Antigens on Cell Surface with Lipid-Encapsulated Fluorescent Nanodiamonds.

Quantifying the density and locating the position of antigens on cell surface has been a challenge in molecular biology research. The challenge lies in the need for a chemically and photophysically stable fluorophore to achieve the required sensitivity and accuracy. Here, we present a method suitable for the purpose by using lipid-encapsulated fluorescent nanodiamonds (FNDs) of 35 nm in diameter as biolabels. The encapsulation of FNDs in biotinylated phospholipids not only facilitates good dispersion of the particles in biological buffers, but also endows them with high specific targeting ability. We demonstrated a viable application of the technique for biotin-mediated immunostaining of antigens on fixed human cells, identifying their positions by two-color confocal fluorescence imaging, and determining their densities by magnetically modulated fluorescence detection. A binding capacity of 6 ± 1 × 104 antigens/cell was measured specifically for CD44 on HeLa cell surface. The result agreed well with the assay of R-phycoerythrin-conjugated antibodies by flow cytometry, supporting the reliability of this new nanoparticle-based method.