Immunomagnetic microscopy of tumor tissues using quantum sensors in diamond.

Histological imaging is essential for the biomedical research and clinical diagnosis of human cancer. Although optical microscopy provides a standard method, it is a persistent goal to develop new imaging methods for more precise histological examination. Here, we use nitrogen-vacancy centers in diamond as quantum sensors and demonstrate micrometer-resolution immunomagnetic microscopy (IMM) for human tumor tissues. We immunomagnetically labeled cancer biomarkers in tumor tissues with magnetic nanoparticles and imaged them in a 400-nm resolution diamond-based magnetic microscope. There is barely magnetic background in tissues, and the IMM can resist the impact of a light background. The distribution of biomarkers in the high-contrast magnetic images was reconstructed as that of the magnetic moment of magnetic nanoparticles by employing deep-learning algorithms. In the reconstructed magnetic images, the expression intensity of the biomarkers was quantified with the absolute magnetic signal. The IMM has excellent signal stability, and the magnetic signal in our samples had not changed after more than 1.5 y under ambient conditions. Furthermore, we realized multimodal imaging of tumor tissues by combining IMM with hematoxylin-eosin staining, immunohistochemistry, or immunofluorescence microscopy in the same tissue section. Overall, our study provides a different histological method for both molecular mechanism research and accurate diagnosis of human cancer.

Magnetic Nanoparticles: A Review on Synthesis, Characterization, Functionalization, and Biomedical Applications.

Nowadays, magnetic nanoparticles (MNPs) are applied in numerous fields, especially in biomedical applications. Since biofluidic samples and biological tissues are nonmagnetic, negligible background signals can interfere with the magnetic signals from MNPs in magnetic biosensing and imaging applications. In addition, the MNPs can be remotely controlled by magnetic fields, which make it possible for magnetic separation and targeted drug delivery. Furthermore, due to the unique dynamic magnetizations of MNPs when subjected to alternating magnetic fields, MNPs are also proposed as a key tool in cancer treatment, an example is magnetic hyperthermia therapy. Due to their distinct surface chemistry, good biocompatibility, and inducible magnetic moments, the material and morphological structure design of MNPs has attracted enormous interest from a variety of scientific domains. Herein, a thorough review of the chemical synthesis strategies of MNPs, the methodologies to modify the MNPs surface for better biocompatibility, the physicochemical characterization techniques for MNPs, as well as some representative applications of MNPs in disease diagnosis and treatment are provided. Further portions of the review go into the diagnostic and therapeutic uses of composite MNPs with core/shell structures as well as a deeper analysis of MNP properties to learn about potential biomedical applications.

Diamond-Based Nanoscale Quantum Relaxometry for Sensing Free Radical Production in Cells.

Diamond magnetometry makes use of fluorescent defects in diamonds to convert magnetic resonance signals into fluorescence. Because optical photons can be detected much more sensitively, this technique currently holds several sensitivity world records for room temperature magnetic measurements. It is orders of magnitude more sensitive than conventional magnetic resonance imaging (MRI) for detecting magnetic resonances. Here, the use of diamond magnetometry to detect free radical production in single living cells with nanometer resolution is experimentally demonstrated. This measuring system is first optimized and calibrated with chemicals at known concentrations. These measurements serve as benchmarks for future experiments. While conventional MRI typically has millimeter resolution, measurements are performed on individual cells to detect nitric oxide signaling at the nanoscale, within 10-20 nm from the internalized particles localized with a diffraction limited optical resolution. This level of detail is inaccessible to the state-of-the-art techniques. Nitric oxide is detected and the dynamics of its production and inhibition in the intra- and extracellular environment are followed.

Catheter knot around the mitral valve apparatus: An exceptional complication of remote magnetic navigation.

Remote magnetic navigation (RMN) is as safe and effective as manual navigation for catheter ablation of ventricular arrhythmias. This case is the first description of a soft-tip ablation catheter entrapment in the mitral valve apparatus during an RMN ablation procedure. The tight knot created by the catheter around a mitral valve chordae required surgical removal. This complication, which has never been reported before, highlights the need for closer fluoroscopic monitoring when performing catheter loops inside the ventricles when using the RMN system.

Magnetic nanoparticles coated with carboxylate-terminated carbosilane dendrons as a reusable and green approach to extract/purify proteins.

Extraction/purification of proteins, at both analytical and industrial levels, is a limiting step that usually requires the use of organic solvents and involves tedious work and a high cost. This work proposes a more sustainable alternative based on the use of magnetic nanoparticles (MNPs) coated with carboxylate-terminated carbosilane dendrons. MNPs coated with first- and second-generation carbosilane dendrons and bare MNPs were employed for the extraction of proteins with different molecular weights and charges. Interaction of proteins with MNPs significantly varied with the pH, the protein, and the dendron generation (different sizes and number of charges in the periphery). Optimal dendron:protein molar ratios and suitable conditions for disrupting interactions after protein extraction were also researched. Second-generation dendron-coated MNPs showed 100% retention capability for all proteins when using acidic conditions. They were reused without losing magnetism or interaction capacity after a disruption of protein-dendron interactions with 0.2% SDS at 100 °C for 10 min. The capacity of dendron-coated MNPs was successfully applied to the recovery/purification of proteins from two food by-products, olive seeds and cheese whey.

A rapid magnetic bead-based immunoassay for sensitive determination of diclofenac.

Increasing contamination of environmental waters with pharmaceuticals represents an emerging threat for the drinking water quality and safety. In this regard, fast and reliable analytical methods are required to allow quick countermeasures in case of contamination. Here, we report the development of a magnetic bead-based immunoassay (MBBA) for the fast and cost-effective determination of the analgesic diclofenac (DCF) in water samples, based on diclofenac-coupled magnetic beads and a robust monoclonal anti-DCF antibody. A novel synthetic strategy for preparation of the beads resulted in an assay that enabled for the determination of diclofenac with a significantly lower limit of detection (400 ng/L) than the respective enzyme-linked immunosorbent assay (ELISA). With shorter incubation times and only one manual washing step required, the assay demands for remarkably shorter time to result (< 45 min) and less equipment than ELISA. Evaluation of assay precision and accuracy with a series of spiked water samples yielded results with low to moderate intra- and inter-assay variations and in good agreement with LC-MS/MS reference analysis. The assay principle can be transferred to other, e.g., microfluidic, formats, as well as applied to other analytes and may replace ELISA as the standard immunochemical method.

Solid-phase extraction methods for nucleic acid separation. A review.

The separation and purification of biomacromolecules such as nucleic acid is a perpetual topic in separation processes and bioengineering (fine chemicals, biopharmaceutical engineering, diagnostics, and biological characterization). In principle, the solid-phase extraction for nucleic acid exhibits efficient phase separation, low pollution risk, and small sample demand, compared to the conventional liquid-phase extraction. Herein, solid-phase extraction methods are systematically reviewed to outline research progress and explore additional solid-phase sorbents and devices for novel, flexible, and high-efficiency nucleic acid separation processes. The functional materials capture nucleic acid, magnetic and magnetic-free solid-phase extraction methods, separation device design and optimization, and high-throughput automatable applications based on high-performance solid-phase extraction are summarized. Finally, the current challenges and promising topics are discussed.

The First Evaluation of Remote Magnetic Navigation-Guided Pediatric Ventricular Arrhythmia Ablation.

Catheter ablation (CA) is an important treatment option for ventricular arrhythmias (VA) in pediatric cardiology. Currently, various CA techniques are available, including remote magnetic navigation (RMN)-guided radiofrequency (RF) ablation. However, no studies evaluate RMN-guided ablative therapy outcomes in children with VA yet. This study aimed to compare procedural and long-term outcomes between RMN-guided and manual (MAN)-guided VA ablation in children. This single-center, retrospective study included all CA procedures for VA performed in children with or without structural heart disease from 2008 until 2020. Two study groups were defined by CA technique: RMN or MAN. Primary outcome was recurrence of VA. Baseline clinical, procedural and safety data were also evaluated. This study included 22 patients, who underwent 30 procedures, with a median age of 15 (IQR 14-17; range 1-17) years and a mean weight of 57 ± 20 kg. In total, 14 procedures were performed using RMN and 16 using MAN (22 first and 8 redo procedures). Regarding first procedures, recurrence rates were significantly lower in RMN compared to MAN (20% versus 67%, P = 0.029), at a mean follow-up of 5.2 ± 3.0 years. Moreover, fluoroscopy dosages were significantly lower in RMN compared to MAN [20 (IQR 14-54) versus 48 (IQR 38-62) mGy, P = 0.043]. In total, 20 patients (91%) were free of VA following their final ablation procedure. This is the first study to investigate the use of RMN in pediatric VA ablation. RMN showed improved outcomes compared to MAN, resulting in lower VA recurrence and reduced fluoroscopy exposure.

Core-shell-structured magnetic covalent organic frameworks for effective extraction of parabens prior to their determination by HPLC.

Covalent organic framework (COF)-decorated magnetic nanoparticles (Fe3O4@DhaTab) with core-shell structure have been synthesized by one-pot method. The prepared Fe3O4@DhaTab was well characterized, and parameters of magnetic solid-phase extraction (MSPE) for parabens were also investigated in detail. Under optimized conditions, the adsorbent dosage was only 3 mg and extraction time was 10 min. The developed Fe3O4@DhaTab-based MSPE-HPLC analysis method offered good linearity (0.01-20 µg mL-1) with R2 (0.999) and low limits of detection (3.3-6.5 µg L-1) using UV detector at 254 nm. The proposed method was applied to determine four parabens in environmental water samples with recoveries in the range 64.0-105% and relative standard deviations of 0.16-7.8%. The adsorption mechanism was explored and indicated that porous DhaTab shell provided π-π, hydrophobic, and hydrogen bonding interactions in the MSPE process. The results revealed the potential of magnetic-functionalized COFs in determination of environmental contaminants.

Magnetic supercluster particles for highly sensitive magnetic biosensing of proteins.

A strategy is reported to improve the detection limits of current giant magnetoresistance (GMR) biosensors by augmenting the effective magnetic moment that the magnetic tags on the biosensors can exert. Magnetic supercluster particles (MSPs), each of which consists of ~ 1000 superparamagnetic cores, are prepared by a wet-chemical technique and are utilized to improve the limit of detection of GMR biosensors down to 17.6 zmol for biotin as a target molecule. This value is more than four orders of magnitude lower than that of the conventional colorimetric assay performed using the same set of reagents except for the signal transducer. The applicability of MSPs in immunoassay is further demonstrated by simultaneously detecting vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) in a duplex assay format. MSPs outperform commercially available magnetic nanoparticles in terms of signal intensity and detection limit.

Probing Magnetic Defects in Ultra-Scaled Nanowires with Optically Detected Spin Resonance in Nitrogen-Vacancy Center in Diamond.

Magnetic nanowires (NWs) are essential building blocks of spintronics devices as they offer tunable magnetic properties and anisotropy through their geometry. While the synthesis and compositional control of NWs have seen major improvements, considerable challenges remain for the characterization of local magnetic features at the nanoscale. Here, we demonstrate nonperturbative field distribution mapping in ultrascaled magnetic nanowires with diameters down to 6 nm by scanning nitrogen-vacancy magnetometry. This enables localized, minimally invasive magnetic imaging with sensitivity down to 3 µT Hz-1/2. The imaging reveals the presence of weak magnetic inhomogeneities inside in-plane magnetized nanowires that are largely undetectable with standard metrology and can be related to local fluctuations of the NWs' saturation magnetization. In addition, the strong magnetic field confinement in the nanowires allows for the study of the interaction between the stray magnetic field and the nitrogen-vacancy sensor, thus clarifying the contrasting formation mechanisms for technologically relevant magnetic nanostructures.

Screening value for gastrointestinal lesions of magnetic-controlled capsule endoscopy in asymptomatic individuals.

BACKGROUND AND AIM: Most patients with gastric tumors and precancerous lesions are asymptomatic, which often results in delayed diagnosis and treatment. Compared with conventional gastroscopy and capsule endoscopy, magnetic-controlled capsule endoscopy is a non-invasive, effective, and cost-efficient diagnostic modality for gastric examination. We retrospectively investigated magnetic-controlled capsule endoscopy as a screening tool for gastrointestinal lesions (particularly gastric tumors and precancerous lesions) in asymptomatic individuals. METHODS: In this retrospective study, 1757 patients who voluntarily underwent magnetic-controlled capsule endoscopy between January and December 2019 at nine medical centers across Shaanxi province based on strict inclusion and exclusion criteria were enrolled. The primary outcomes were gastric tumor and precancerous lesion detection rates and procedural safety. RESULTS: The upper and lower gastrointestinal lesion detection rates were 98.35% (1728/1757) and 21.61% (78/361), respectively; 2.28% of patients were diagnosed with gastric tumors including gastric cancer (4/1757) and submucosal tumors (36/1757). Three types of precancerous lesions were found in 591 patients (33.64%), including chronic atrophic gastritis (23.16%), gastric polyp (10.98%), and gastric ulcer (2.96%). For patients aged over 40 years, the detection rate of precancerous lesions was higher (14.36% vs 42.58%, P < 0.001). No patient was diagnosed with small intestinal cancer. No adverse events occurred. CONCLUSIONS: Magnetic-controlled capsule endoscopy could be used as a promising novel screening modality for diagnosis of gastrointestinal lesions in asymptomatic individuals, specifically gastric tumors and precancerous lesions, with the advantages of safety, non-invasiveness, effectiveness, and cost-efficiency.

Immunoengineered magnetic-quantum dot nanobead system for the isolation and detection of circulating tumor cells.

BACKGROUND: Highly efficient capture and detection of circulating tumor cells (CTCs) remain elusive mainly because of their extremely low concentration in patients' peripheral blood. METHODS: We present an approach for the simultaneous capturing, isolation, and detection of CTCs using an immuno-fluorescent magnetic nanobead system (iFMNS) coated with a monoclonal anti-EpCAM antibody. RESULTS: The developed antibody nanobead system allows magnetic isolation and fluorescent-based quantification of CTCs. The expression of EpCAM on the surface of captured CTCs could be directly visualized without additional immune-fluorescent labeling. Our approach is shown to result in a 70-95% capture efficiency of CTCs, and 95% of the captured cells remain viable. Using our approach, the isolated cells could be directly used for culture, reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry (ICC) identification. We applied iFMNS for testing CTCs in peripheral blood samples from a lung cancer patient. CONCLUSIONS: It is suggested that our iFMNS approach would be a promising tool for CTCs enrichment and detection in one step.

Hydrophilic molecularly imprinted polymers functionalized magnetic carbon nanotubes for selective extraction of cyclic adenosine monophosphate from winter jujube.

In this work, a green strategy was developed to prepare molecularly imprinted polymers functionalized magnetic carbon nanotubes in aqueous phase under mild conditions for cyclic adenosine monophosphate. Thanks to water solubility of chitosan, a natural polysaccharide which is rich in amino and hydroxyl groups, provided the feasibility to synthesize the green molecularly imprinted polymers for water soluble template in aqueous media. Coupled with high-performance liquid chromatography, the method exhibited a short equilibrium time (6 min), high adsorption capacity (22.42 µg/mg), high magnetic susceptibility, and good selectivity to template molecule with the imprinting factor of 2.94. A good linearity in the range of 0.020-3.0 mg/mL for target was obtained with a correlation coefficient of 0.9998. The limit of detection (signal-to-noise ratio = 3) and limit of quantitation (signal-to-noise ratio = 10) of the magnetic solid phase extraction method for cyclic adenosine monophosphate were 5 and 15 ng/mg, respectively. And the practical application of chitosan-based molecularly imprinted polymers as adsorbent to isolate and determine cyclic adenosine monophosphate in real natural samples (winter jujube) was demonstrated.

Extraction of human noroviruses from leafy greens and fresh herbs using magnetic silica beads.

Consumption of leafy greens and to a lesser extent fresh herbs has been associated with several foodborne outbreaks including human norovirus (HuNoV). However, the extraction and detection of viruses from these matrices present multiple challenges such as low recovery yields and relatively high PCR inhibition. A new magnetic silica bead based (MSB) extraction protocol was developed and used to recover norovirus from leafy greens and fresh herbs. The performance results were compared to the ISO 15216-1:2017 standard. The HuNoV GII.4 and GI.5 recovery yields from spiked lettuce using the MSB extraction protocol range from 33 to 82%. There was a good correlation between murine norovirus (MNV) and HuNoV recovery yields from fresh herbs and leafy greens. No reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) inhibition was detected from leafy green extracts using the MSB methodology. The selected commercial RT-qPCR detection kit had a major impact on RT-qPCR inhibition levels detected in the ISO 15216-1:2017 RNA extracts. RNase treatment was used to estimate genome recovery from HuNoV with intact capsids. This treatment resulted in similar HuNoV and MNV recovery yields. Between 2019 and 2020, the MSB protocol was used to conduct a survey of HuNoV in domestic and imported leafy greens and fresh herbs sold at retail in Canada. All of the 280 samples tested were negative. Overall, the use of MSB was shown to be an efficient approach to recover HuNoV from leafy greens and certain types of fresh herbs and to conduct surveys.

Magnetic map in nonanadromous Atlantic salmon.

Long-distance migrants, including Pacific salmon (Oncorhynchus spp), can use geomagnetic information to navigate. We tested the hypothesis that a "magnetic map" (i.e., an ability to extract positional information from Earth's magnetic field) also exists in a population of salmon that do not undertake oceanic migrations. This study examined juvenile Atlantic salmon (Salmo salar) originally from a nonanadromous population in Maine transferred ∼60 years ago to a lake in central Oregon. We exposed juveniles to magnetic displacements representative of locations at the latitudinal boundaries of the Pacific salmon oceanic range in the North Pacific and at the periphery of their ancestral oceanic range in the North Atlantic. Orientation differed among the magnetic treatments, indicating that Atlantic salmon detect map information from the geomagnetic field. Despite no recent history of ocean migration, these fish displayed adaptive orientation responses similar to those observed in native Pacific salmonids. These findings indicate that use of map information from the geomagnetic field is a shared ancestral character in the family Salmonidae and is not restricted to populations with anadromous life histories. Lastly, given that Atlantic salmon are transported throughout the world for capture fisheries and aquaculture, such a robust navigational system is of some concern. Escaped individuals may have greater potential to successfully navigate, and thus invade, introduced habitats than previously suspected.

Radio frequency plasma assisted surface modification of Fe3O4 nanoparticles using polyaniline/polypyrrole for bioimaging and magnetic hyperthermia applications.

Surface modification of superparamagnetic Fe3O4 nanoparticles using polymers (polyaniline/polypyrrole) was done by radio frequency (r.f.) plasma polymerization technique and characterized by XRD, TEM, TG/DTA and VSM. Surface-passivated Fe3O4 nanoparticles with polymers were having spherical/rod-shaped structures with superparamagnetic properties. Broad visible photoluminescence emission bands were observed at 445 and 580 nm for polyaniline-coated Fe3O4 and at 488 nm for polypyrrole-coated Fe3O4. These samples exhibit good fluorescence emissions with L929 cellular assay and were non-toxic. Magnetic hyperthermia response of Fe3O4 and polymer (polyaniline/polypyrrole)-coated Fe3O4 was evaluated and all the samples exhibit hyperthermia activity in the range of 42-45 °C. Specific loss power (SLP) values of polyaniline and polypyrrole-coated Fe3O4 nanoparticles (5 and 10 mg/ml) exhibit a controlled heat generation with an increase in the magnetic field.

Modifications of EHPDB Physical Properties through Doping with Fe2O3 Nanoparticles (Part II).

The aim of our study was to analyze the influence of various concentrations of γ-Fe2O3 nanoparticles on the physical properties of the liquid crystalline ferroelectric SmC* phase, as well as to check the effect of introducing nanoparticles in the LC matrix on their properties in the prepared five nanocomposites. UV-vis spectroscopy showed that the admixture reduced the absorption of nanocomposites in the UV range, additional absorption bands appeared, and all nanocomposites were transparent in the range of 500-850 nm. The molecular dynamics in particular phases of the nanocomposites were investigated by the dielectric spectroscopy method, and it was found that nanoparticles caused a significant increase in the dielectric constant at low frequencies, a strong modification of the dielectric processes in the SmC* phase, and the emergence of new relaxation processes for the highest dopant concentrations. SQUID magnetometry allowed us to determine the magnetic nature of the nanoparticles used, and to show that the blocked state of nanoparticles was preserved in nanocomposites (hysteresis loops were also registered in the ferroelectric SmC* phase). The dependence of the coercive field on the admixture concentration and the widening of the hysteresis loop in nanocomposites in relation to pure nanoparticles were also found. In turn, the FT-MIR spectroscopy method was used to check the influence of the impurity concentration on the formation/disappearance or modification of the absorption bands, and the modification of both the FWHM and the maximum positions for the four selected vibrations in the MIR range, as well as the discontinuous behavior of these parameters at the phase transitions, were found.

A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy.

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.

Effect of Polymer Removal on the Morphology and Phase of the Nanoparticles in All-Inorganic Heterostructures Synthesized via Two-Step Polymer Infiltration.

Polymer templates play an essential role in the robust infiltration-based synthesis of functional multicomponent heterostructures with controlled structure, porosity, and composition. Such heterostructures are be used as hybrid organic-inorganic composites or as all-inorganic systems once the polymer templates are removed. Using iron oxide/alumina heterostructures formed by two-step infiltration of polystyrene-block-polyvinyl pyridine block copolymer with iron and aluminum precursors from the solution and vapor-phases, respectively, we show that the phase and morphology of iron oxide nanoparticles dramatically depend on the approach used to remove the polymer. We demonstrate that thermal and plasma oxidative treatments result in iron oxide nanoparticles with either solid or hollow morphologies, respectively, that lead to different magnetic properties of the resulting materials. Our study extends the boundaries of structure manipulations in multicomponent heterostructures synthesized using polymer infiltration synthesis, and hence their properties.