On-Chip Magnetic Extraction of Circulating Cell-Free DNA from Biological Samples.

In recent years, the analysis of circulating cell-free DNA (cfDNA) containing tumor-derived DNA has emerged as a noninvasive means for cancer monitoring and personalized medicine. However, the isolation of cfDNA from peripheral blood has remained a challenge due to the low abundance and high fragmentation of these molecules. Here, we present a dynamic Magnetic ExTRactiOn (METRO) protocol using microfluidic fluidized bed technology to isolate circulating cfDNA from raw biological materials such as undiluted serum. This protocol maximizes the surface area for DNA binding within the chip in order to capture short DNA fragments. It uses only a few µL of sample and reagents. The protocol can be automated, and it is fully compatible with sensitive DNA amplification methods such as droplet-based digital PCR (ddPCR).

Autonomous Magnetic Navigation in Endoscopic Image Mosaics.

Endoscopes navigate within the human body to observe anatomical structures with minimal invasiveness. A major shortcoming of their use is their narrow field-of-view during navigation in large, hollow anatomical regions. Mosaics of endoscopic images can provide surgeons with a map of the tool's environment. This would facilitate procedures, improve their efficiency, and potentially generate better patient outcomes. The emergence of magnetically steered endoscopes opens the way to safer procedures and creates an opportunity to provide robotic assistance both in the generation of the mosaic map and in navigation within this map. This paper proposes methods to autonomously navigate magnetic endoscopes to 1) generate endoscopic image mosaics and 2) use these mosaics as user interfaces to navigate throughout the explored area. These are the first strategies, which allow autonomous magnetic navigation in large, hollow organs during minimally invasive surgeries. The feasibility of these methods is demonstrated experimentally both in vitro and ex vivo in the context of the treatment of twin-to-twin transfusion syndrome. This minimally invasive procedure is performed in utero and necessitates coagulating shared vessels of twin fetuses on the placenta. A mosaic of the vasculature in combination with autonomous navigation has the potential to significantly facilitate this challenging surgery.

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.

A phage-based magnetic relaxation switching biosensor using bioorthogonal reaction signal amplification for Salmonella detection in foods.

Phages are uniquely suited for bacterial detection due to their low cost and ability to recognize live bacteria. Herein, our work establishes the proof-of-concept detection of Salmonella in orange juice based on a phage-mediated portable magnetic relaxation switching (MRS) biosensor. The limit of quantification (LOQ) could reach 5 CFU/mL (95 % confidence interval [CI]: 4-7, N = 4) with a linear range of 102-108 CFU/mL, which has improved 10-fold than that without bioorthogonal signal amplification. The recovery rate of the phage-based MRS biosensor was 95.0 % (95 % confidence interval [CI]: 89.0 %-100.9 %, N = 6). The specificity of the phage-based MRS biosensor was 100 % without false-positive results. In addition, this sensor was able to detect <10 CFU per 25 mL of Salmonella in orange juice with 4-h pre-enrichment. The result from the phage-based MRS biosensor is consistent with that from the standard plate count method. This sensor provides a reliable and ultrasensitive detection platform for pathogens.

Biosensors and Drug Delivery in Oncotheranostics Using Inorganic Synthetic and Biogenic Magnetic Nanoparticles.

Magnetic nanocarriers have attracted attention in translational oncology due to their ability to be employed both for tumor diagnostics and therapy. This review summarizes data on applications of synthetic and biogenic magnetic nanoparticles (MNPs) in oncological theranostics and related areas. The basics of both types of MNPs including synthesis approaches, structure, and physicochemical properties are discussed. The properties of synthetic MNPs and biogenic MNPs are compared with regard to their antitumor therapeutic efficiency, diagnostic potential, biocompatibility, and cellular toxicity. The comparative analysis demonstrates that both synthetic and biogenic MNPs could be efficiently used for cancer theranostics, including biosensorics and drug delivery. At the same time, reduced toxicity of biogenic particles was noted, which makes them advantageous for in vivo applications, such as drug delivery, or MRI imaging of tumors. Adaptability to surface modification based on natural biochemical processes is also noted, as well as good compatibility with tumor cells and proliferation in them. Advances in the bionanotechnology field should lead to the implementation of MNPs in clinical trials.

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.

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.

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 particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality.

Magnetic particle imaging (MPI) is an emerging tracer-based modality that enables real-time three-dimensional imaging of the non-linear magnetisation produced by superparamagnetic iron oxide nanoparticles (SPIONs), in the presence of an external oscillating magnetic field. As a technique, it produces highly sensitive radiation-free tomographic images with absolute quantitation. Coupled with a high contrast, as well as zero signal attenuation at-depth, there are essentially no limitations to where that can be imaged within the body. These characteristics enable various biomedical applications of clinical interest. In the opening sections of this review, the principles of image generation are introduced, along with a detailed comparison of the fundamental properties of this technique with other common imaging modalities. The main feature is a presentation on the up-to-date literature for the development of SPIONs tailored for improved imaging performance, and developments in the current and promising biomedical applications of this emerging technique, with a specific focus on theranostics, cell tracking and perfusion imaging. Finally, we will discuss recent progress in the clinical translation of MPI. As signal detection in MPI is almost entirely dependent on the properties of the SPION employed, this work emphasises the importance of tailoring the synthetic process to produce SPIONs demonstrating specific properties and how this impacts imaging in particular applications and MPI's overall performance.

Physical Bases, Indications, and Results of the Use of Magnets in Digestive Surgery: A Narrative Review.

Background: The use of magnetic devices in digestive surgery has been a matter of debate in recent years. The aim of this review was to describe the physical bases, indications, and results of the use of magnets in digestive surgery. Methods: A review of the literature was performed using Scopus, PubMed, ScienceDirect, and SciELO databases considering as inclusion criteria all articles published since 2007 to date, describing the physical basis of magnetic assisted surgery and those that describe the surgical procedure, including case reports, as well as, articles on humans and experimental animals. Results: Sixty-four studies were included, 15 detailing aspects on the physical basis and 49 about indications and results. Magnets are currently used to perform fixed traction, mobilizing structures, and anastomosis in humans and experimental animals. Conclusions: The use of magnets in digestive surgery has shown good results, and no complications arising from their use have been reported. However, more prospective and randomized studies that compare magnetic surgery and conventional techniques are needed.

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 mediators for ultrasound theranostics.

The theranostics paradigm is based on the concept of combining therapeutic and diagnostic modalities into one platform to improve the effectiveness of treatment. Combinations of multiple modalities provide numerous medical advantages and are enabled by nano- and micron-sized mediators. Here we review recent advancements in the field of ultrasound theranostics and the use of magnetic materials as mediators. Several subdisciplines are described in detail, including controlled drug delivery and release, ultrasound hyperthermia, magneto-ultrasonic heating, sonodynamic therapy, magnetoacoustic imaging, ultrasonic wave generation by magnetic fields, and ultrasound tomography. The continuous progress and improvement in theranostic materials, methods, and physical computing models have created undeniable possibilities for the development of new approaches. We discuss the prospects of ultrasound theranostics and possible expansions of other studies to the theranostic context.

Magnetically sensitive nanocomplex enhances antitumor efficacy of dendritic cell-based immunotherapy.

BACKGROUND: One of the major factors restricting in vivo efficacy of dendritic cells (DCs) based immunotherapy is the inefficient migration of these cells to the lymphoid tissue, wherein DCs activate antigen-specific T cells. A fundamentally new approach for the possibility of enhancing the antitumor effects of DC-based immunotherapy may be the use of magnetically sensitive nanocomplexes to increase the target delivery of DCs to the lymph nodes of the recipient. AIM: To study the antitumor and immunomodulatory effects of the DC-nanovaccine with magnetosensitive properties and its influence on the immunosuppressive tumor microenvironment in mice with sarcoma 37. MATERIALS AND METHODS: The antitumor, antimetastatic and immunomodulatory effects of DCs loaded with magnetic nanocomplex under magnetic field (MF) control in mice with sarcoma 37 have been investigated. RESULTS: Combined therapy contributed to a significant reduction in tumor volume and weight compared to the control group of mice and mice that received the DC vaccine without MF. Therapy with magnetically sensitive DC nanovaccine with and without the addition of the MF was accompanied by a significant down-regulation of the level of FoxP3, transforming growth factor ß, interleukin (IL)-10 and vascular endothelial growth factors, mRNA expression in tumor tissues. A significant increase in interferon-γ and IL-4 mRNA expression was found in mice treated with the magnetically sensitive DC nanovaccine under MF control. CONCLUSION: A significant increase in the antitumor efficacy of the DC vaccine can be achieved using magnetosensitive nanocarriers of tumor antigens under MF control.

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.

Rapid determination of folic acid and riboflavin in urine by polypyrrole magnetic solid-phase extractant combined ultra-performance liquid chromatography.

Determination of folic acid and riboflavin in biological samples is difficult due to their high polarity, low concentration, chemical instability, and complex matrix. In this study, the polypyrrole-coated magnetic nanocomposite (Fe3O4@PPy) was synthesized innovatively with the assistance of hexadecyltrimethylammonium bromide. To evaluate the adsorption mechanism and the feasibility of synthesized Fe3O4@PPy as an adsorbent, the adsorption capacities, kinetics and thermodynamics of folic acid and riboflavin were investigated systemically. Furthermore, in light of the chemical instability of folic acid and riboflavin a method for rapid extraction and detection of them from human urine within 10 min was developed successfully by combining magnetic solid phase extraction with ultra-performance liquid chromatography (MSPE/UPLC). The adsorption parameters including sorbent amount, pH value, extraction time, desorption solvent and desorption time were studied. Under optimum conditions, the performance of the established determination method was validated with the linearly dependent coefficients (>0.9995), the limits of detection (0.02-0.05 µg/mL), the limits of quantification (0.07-0.18 µg/mL), and the recoveries (92.2-105.1%, with relative standard deviation < 3.3%). The rapid extraction and detection of folic acid and riboflavin from real urine samples were achieved subsequently. The present study suggests that the developed method exhibits a promising application in the analysis of free folic acid and riboflavin in human urine samples, which can provide a reference for the clinical drug monitoring and treatment.

Biomechanical sensing of in vivo magnetic nanoparticle hyperthermia-treated melanoma using magnetomotive optical coherence elastography.

Rationale: Magnetic nanoparticle hyperthermia (MH) therapy is capable of thermally damaging tumor cells, yet a biomechanically-sensitive monitoring method for the applied thermal dosage has not been established. Biomechanical changes to tissue are known indicators for tumor diagnosis due to its association with the structural organization and composition of tissues at the cellular and molecular level. Here, by exploiting the theranostic functionality of magnetic nanoparticles (MNPs), we aim to explore the potential of using stiffness-based metrics that reveal the intrinsic biophysical changes of in vivo melanoma tumors after MH therapy. Methods: A total of 14 melanoma-bearing mice were intratumorally injected with dextran-coated MNPs, enabling MH treatment upon the application of an alternating magnetic field (AMF) at 64.7 kHz. The presence of the MNP heating sources was detected by magnetomotive optical coherence tomography (MM-OCT). For the first time, the elasticity alterations of the hyperthermia-treated, MNP-laden, in vivo tumors were also measured with magnetomotive optical coherence elastography (MM-OCE), based on the mechanical resonant frequency detected. To investigate the correlation between stiffness changes and the intrinsic biological changes, histopathology was performed on the excised tumor after the in vivo measurements. Results: Distinct shifts in mechanical resonant frequency were observed only in the MH-treated group, suggesting a heat-induced stiffness change in the melanoma tumor. Moreover, tumor cellularity, protein conformation, and temperature rise all play a role in tumor stiffness changes after MH treatment. With low cellularity, tumor softens after MH even with low temperature elevation. In contrast, with high cellularity, tumor softening occurs only with a low temperature rise, which is potentially due to protein unfolding, whereas tumor stiffening was seen with a higher temperature rise, likely due to protein denaturation. Conclusions: This study exploits the theranostic functionality of MNPs and investigates the MH-induced stiffness change on in vivo melanoma-bearing mice with MM-OCT and MM-OCE for the first time. It was discovered that the elasticity alteration of the melanoma tumor after MH treatment depends on both thermal dosage and the morphological features of the tumor. In summary, changes in tissue-level elasticity can potentially be a physically and physiologically meaningful metric and integrative therapeutic marker for MH treatment, while MM-OCE can be a suitable dosimetry technique.

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.

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.

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.

Magnetic ligand fishing using immobilized DPP-IV for identification of antidiabetic ligands in lingonberry extract.

In this work, a new magnetic ligand fishing probe for discovery of DPP-IV inhibitory ligands was developed and it was tested as a proof of concept on the fruit extract of Vaccinium vitis-idaea (lingonberry). The ligands were shown to have appreciable dipeptidyl peptidase IV (DPP-IV) inhibitory activity (IC50: 31.8 µg mL-1).) Inhibition of DPP-IV is a well-known therapeutic approach for management of type 2 diabetes (T2D). DPP-IV was successfully immobilized onto magnetic beads and was shown to retain its catalytic activity and selectivity over a model mixture. A total of four ligands were successfully fished out and identified as cyanidin-3-galactoside (2), cyanidin-3-arabinoside (3), proanthocynidin A (4), and 10-carboxyl-pyranopeonidin 3-O-(6″-O-p-coumaroyl)-glucoside (5) using HPLC/HRMS.