Versatile and Accessible Magnetic Diagnosis Platform with Different Types of Magnetic Particles for Liquid and Solid Biopsies.

The diagnosis of liquid and solid biopsies by different instruments makes the clinic loading difficult in many aspects. Given the compositions of magnetic particles (MPs) with diverse characterizations and the innovative acoustic type of vibration sample magnetometer (VSM), the versatile, accessible magnetic diagnosis platform was proposed to meet clinical demands, such as low loading for multiple biopsies. In liquid biopsies of alpha-fetoprotein (AFP) standard solutions and subject serums, molecular concentration was analyzed from saturation magnetization by the soft type of Fe3O4 MPs with AFP bioprobe coating. In the phantom mixture simulated as bounded MPs in tissue, the bounded MPs was evaluated from the area of the hysteresis loop by hard type of cobalt MPs without bio-probes coating. Not only a calibration curve was founded for many hepatic cell carcinoma stages, but also microscale images verified the Ms increase due to magnetic protein clusters, etc. Hence, its wide populations in clinics could be expected.

Synthesised Conductive/Magnetic Composite Particles for Magnetic Ablations of Tumours.

Ablation is a clinical cancer treatment, but some demands are still unsatisfied, such as electromagnetic interferences amongst multiple ablation needles during large tumour treatments. This work proposes a physical synthesis for composite particles of biocompatible iron oxide particles and liquid metal gallium (Ga) with different alternative-current (AC)-magnetic-field-induced heat mechanisms of magnetic particle hyperthermia and superior resistance heat. By some imaging, X-ray diffraction, and vibrating sample magnetometer, utilised composite particles were clearly identified as the cluster of few iron oxides using the small weight ratio of high-viscosity liquid metal Ga as conjugation materials without surfactants for physical targeting of limited fluidity. Hence, well penetration inside the tissue and the promotion rate of heat generation to fit the ablation requirement of at least 60 °C in a few seconds are achieved. For the injection and the post-injection magnetic ablations, the volume variation ratios of mice dorsal tumours on Day 12 were expressed at around one without tumour growth. Its future powerful potentiality is expected through a percutaneous injection.

Highly efficient magnetic ablation and the contrast of various imaging using biocompatible liquid-metal gallium.

BACKGROUND: Although the powerful clinical effects of radiofrequency and microwave ablation have been established, such ablation is associated with several limitations, including a small ablation size, a long ablation time, the few treatment positioning, and biosafety risks. To overcome these limitations, biosafe and efficient magnetic ablation was achieved in this study by using biocompatible liquid gallium as an ablation medium and a contrast medium for imaging. RESULTS: Magnetic fields with a frequency (f) lower than 200 kHz and an amplitude (H) × f value lower than 5.0 × 109 Am-1 s-1 were generated using the proposed method. These fields could generate an ablation size of 3 cm in rat liver lobes under a temperature of approximately 300 °C and a time of 20 s. The results of this study indicate that biomedical gallium can be used as a contrast medium for the positioning of gallium injections and the evaluation of ablated tissue around a target site. Liquid gallium can be used as an ablation medium and imaging contrast medium because of its stable retention in normal tissue for at least 3 days. Besides, the high anticancer potential of gallium ions was inferred from the self-degradation of 100 µL of liquid gallium after around 21 days of immersion in acidic solutions. CONCLUSIONS: The rapid wireless ablation of large or multiple lesions was achieved through the simple multi-injection of liquid gallium. This approach can replace the currently favoured procedure involving the use of multiple ablation probes, which is associated with limited benefits and several side effects. METHODS: Magnetic ablation was confirmed to be highly efficient by the consistent results obtained in the simulation and in vitro tests of gallium and iron oxide as well as the electromagnetic specifics and thermotherapy performance comparison detailed in this study Ultrasound imaging, X-ray imaging, and magnetic resonance imaging were found to be compatible with the proposed magnetic ablation method. Self-degradation analysis was conducted by mixing liquid gallium in acidic solutions with a pH of approximately 5-7 (to imitate a tumour-containing microenvironment). X-ray diffraction was used to identify the gallium oxides produced by degraded gallium ions.

Low cost multifunctional 3D printed image quality and dose verification phantom for an image-guided radiotherapy system.

PURPOSE: Image-guided radiation therapy (IGRT) is used to precisely deliver radiation to a tumour to reduce the possible damage to the surrounding normal tissues. Clinics use various quality assurance (QA) equipment to ensure that the performance of the IGRT system meets the international standards set for the system. The objective of this study was to develop a low-cost and multipurpose module for evaluating image quality and dose. METHODS: A multipurpose phantom was designed to meet the clinical requirements of high accuracy, easy setup, and calibration. The outer shell of the phantom was fabricated using acrylic. Three dimensional (3D) printing technology was used to fabricate inner slabs with the characteristics of high spatial resolution, low-contrast detectability, a 3D grid, and liquid-filled uniformity. All materials were compatible with magnetic resonance (MR). Computed tomography (CT) simulator and linear accelerator (LINAC) modules were developed and validated. RESULTS: The uniformity slab filled with water is ideal for the assessment of Hounsfield units, whereas that filled with wax is suitable for consistency checks. The high-spatial-resolution slab enables measurements with a resolution up to 5 lp/cm. The low-contrast detectability slab contains rods of 5 different sizes that can be clearly visualised. These components meet the American College of Radiology (ACR) standards for QA of CT simulators and LINACs. CONCLUSIONS: The multifunctional phantom module meets the ACR recommended QA guidelines and is suitable for both LINACs and CT-sim. Further measurements in an MR simulator and an MR linear accelerator (MR-LINAC) will be arranged in the future.

Improvement of multisource localization of magnetic particles in an animal.

In this simulation work, the linearized Bregman iterative algorithm was applied to solve the magnetic source distribution problem of a magnetic particle imaging (MPI) system for small animals. MPI system can apply an excitation magnetic field, and the induced magnetic field from the magnetic nanoparticles (MNPs) can be detected by the sensors of MPI system. With a gaussian distribution source at the upper side of the mouse brain, sensors set above the mouse brain and the constant excitation magnetic field, the average deviation of the calculated source distribution from the multiplane scanning along the axis away from the mouse brain and the closest plane scanning are 2.78 × 10-3 and 2.84 × 10-3 respectively. The simulated result showed that combination of multiplane scanning hardly improves the accuracy of the source localization. In addition, a gradient scan method was developed that uses gradient magnetic field to scan the mouse brain. The position of the maximum of the lead field matrix will be controlled by the gradient field. With a set up gaussian distribution source at the bottom of the mouse brain, the average deviation of the calculated source distribution from the gradient scan method and the constant field are 4.42 × 10-2 and 5.05 × 10-2. The location error from the two method are 2.24 × 10-1 cm and 3.61 × 10-1 cm. The simulation showed that this method can improve the accuracy compared to constant field when the source is away from the sensor and having a potential for application.

Design of a motion simulation system to assist respiratory gating for radiation therapy.

Stereotactic ablative radiotherapy (SABR) aims to deliver high doses of radiation to kill cancer cells and shrink tumors in less than or equal to 6 fractions. However, organ motion during treatment is a challenging issue for this kind of technique. We develop a control system via Bluetooth technology to simulate and correct body motion during SABR. METHODS: Radiation doses were analyzed, and the radiation damage protection capability was checked by external beam therapy 3 (EBT3) films irradiated by a linear accelerator. A wireless signal test was also performed. A validation was performed with 8 previously treated patient respiratory pattern records and 8 healthy volunteers. RESULTS: The homemade simulation system consisted of 2 linear actuators, one movable stage with a maximal moving distance of 6.5 cm × 12.5 cm × 5 cm to simulate the respiratory pattern of 8 patients precisely with a median error of 0.36 mm and a maximal motion difference of 1.17 mm, and 3.17 and chipset transited signals to display them as a waveform. From the test with 8 volunteers, the chip could detect deep respiratory movement up to 3 cm. The effect of the chip on a radiation dose of 400 monitor units (MUs) by 6 MV photons and 200 MUs by 10 MV photons showed high penetration rates of 98.8% and 98.6%, respectively. CONCLUSIONS: We invented a tubeless and wireless respiratory gating detection chip. The chip has minimal interference with the treatment angles, good noise immunity and the capability to easily penetrate a variety of materials. The simulation system consisting of linear actuators also successfully simulates the respiratory pattern of real patients.

Eight-Channel AC Magnetosusceptometer of Magnetic Nanoparticles for High-Throughput and Ultra-High-Sensitivity Immunoassay.

An alternating-current magnetosusceptometer of antibody-functionalized magnetic nanoparticles (MNPs) was developed for immunomagnetic reduction (IMR). A high-sensitivity, high-critical-temperature superconducting quantum interference device was used in the magnetosusceptometer. Minute levels of biomarkers of early-stage neurodegeneration diseases were detectable in serum, but measuring each biomarker required approximately 4 h. Hence, an eight-channel platform was developed in this study to fit minimal screening requirements for Alzheimer's disease. Two consistent results were measured for three biomarkers, namely Aß40, Aß42, and tau protein, per human specimen. This paper presents the instrument configuration as well as critical characteristics, such as the low noise level variations among channels, a high signal-to-noise ratio, and the coefficient of variation for the biomarkers' IMR values. The instrument's ultrahigh sensitivity levels for the three biomarkers and the substantially shorter total measurement time in comparison with the previous single- and four-channels platforms were also demonstrated in this study. Thus, the eight-channel instrument may serve as a powerful tool for clinical high-throughput screening of Alzheimer's disease.

Characterizations of Anti-Alpha-Fetoprotein-Conjugated Magnetic Nanoparticles Associated with Alpha-Fetoprotein for Biomedical Applications.

In this work, we report characterizations of biofunctionalized magnetic nanoparticles (BMNPs) associated with alpha-fetoprotein (AFP) for biomedical applications. The example BMNP in this study is anti-alpha-fetoprotein (anti-AFP) conjugated onto dextran-coated Fe3O4 labeled as Fe3O4-anti-AFP, and the target is AFP. We characterize magnetic properties, such as increments of magnetization ΔMH and effective relaxation time Δτeff in the reaction process. It is found that both ΔMH and Δτeff are enhanced when the concentration of AFP, ФAFP, increases. The enhancements are due to magnetic interactions among BMNPs in magnetic clusters, which contribute extra MH after the association with MH and in turn enhance τeff. The screening of patients carrying hepatocellular carcinoma (HCC) is verified via ΔMH/MH. The proposed method can be applied to detect a wide variety of analytes. The scaling characteristics of ΔMH/MH show the potential to develop a vibrating sample magnetometer system with low field strength for clinic applications.

Ultrasound-Induced Magnetic Imaging of Tumors Targeted by Biofunctional Magnetic Nanoparticles.

Biofunctional magnetic nanoparticles (MNPs) have been widely applied in biomedical engineering. MNPs are used as a contrast medium in magnetic imaging. Current methods of magnetic imaging, such as magnetic particle imaging and magnetic relaxometry, use small amounts of MNPs at target points far from the surface of the patient's body; these methods always consume considerable power to produce magnetic fields of high uniformity or gradient excitations. Some drawbacks, such as a limited imaging region, imaging system shielding, and complex algorithms based on assumptions of MNP properties or environmental factors, also limit the application of MNP methods in clinics. Therefore, this work proposes an interdisciplinary methodology of ultrasound-induced magnetic imaging that lacks these drawbacks. In the proposed imaging method, magnet sets were designed with uniform magnetic fields to magnetize MNPs. Besides, magnetized MNPs are subjected to ultrasound vibrations; the motion of the MNPs induces weak induction voltages at the imaging pickup coils. The highly sensitive scanning superconducting quantum interference device biosusceptometry with three sets of ultrasound focus chips was developed to construct magnetic tomography at three depths. A phantom test showed favorable consistency between the visual photos and the magnetic images of alpha-fetoprotein antibody (anti-AFP) MNP distribution on gauzes. In animal tests, rats with liver tumors were imaged at the pre-injection and post-injection of anti-AFP MNPs. The consistent results of magnetic images and ultrasound images implied that the proposed method has high clinical potential.

Rapid and quantitative discrimination of tumour cells on tissue slices.

After a needle biopsy, immunohistochemistry is generally used to stain tissue slices for clinically confirming tumours. Currently, tissue slices are immersed in a bioprobe-linked fluorescent reagent for several minutes, washed to remove the unbound reagent, and then observed using a fluorescence microscope. However, the observation must be performed by experienced pathologists, and producing a qualitative analysis is time consuming. Therefore, this study proposes a novel scanning superconducting quantum interference device biosusceptometry (SSB) method for avoiding these drawbacks. First, stain reagents were synthesised for the dual modalities of fluorescent and magnetic imaging by combining iron-oxide magnetic nanoparticles and the currently used fluorescent reagent. The reagent for the proposed approach was stained using the same procedure as that for the current fluorescent reagent, and tissue slices were rapidly imaged using the developed SSB for obtaining coregistered optical and magnetic images. Analysing the total intensity of magnetic spots in SSB images enables quantitatively determining the tumour cells of tissue slices. To confirm the magnetic imaging results, a traditional observation methodology entailing the use of a fluorescence microscope was also performed as the gold standard. This study determined high consistency between the fluorescent and magnetic spots in different regions of the tissue slices, demonstrating the feasibility of the proposed approach, which will benefit future clinical pathology.

Using bio-functionalized magnetic nanoparticles and dynamic nuclear magnetic resonance to characterize the time-dependent spin-spin relaxation time for sensitive bio-detection.

In this work, we report the use of bio-functionalized magnetic nanoparticles (BMNs) and dynamic magnetic resonance (DMR) to characterize the time-dependent spin-spin relaxation time for sensitive bio-detection. The biomarkers are the human C-reactive protein (CRP) while the BMNs are the anti-CRP bound onto dextran-coated Fe3O4 particles labeled as Fe3O4-antiCRP. It was found the time-dependent spin-spin relaxation time, T2, of protons decreases as time evolves. Additionally, the ΔT2 of of protons in BMNs increases as the concentration of CRP increases. We attribute these to the formation of the magnetic clusters that deteriorate the field homogeneity of nearby protons. A sensitivity better than 0.1 µg/mL for assaying CRP is achieved, which is much higher than that required by the clinical criteria (0.5 mg/dL). The present MR-detection platform shows promise for further use in detecting tumors, viruses, and proteins.

A capillary dielectrophoretic chip for real-time blood cell separation from a drop of whole blood.

This study proposes a capillary dielectrophoretic chip to separate blood cells from a drop of whole blood (approximately 1 µl) sample using negative dielectrophoretic force. The separating efficiency was evaluated by analyzing the image before and after dielectrophoretic force manipulation. Blood samples with various hematocrits (10%-60%) were tested with varied separating voltages and chip designs. In this study, a chip with 50 µm gap design achieved a separation efficiency of approximately 90% within 30 s when the hematocrit was in the range of 10%-50%. Furthermore, glucose concentration was electrochemically measured by separating electrodes following manipulation. The current response increased significantly (8.8-fold) after blood cell separation, which was attributed not only to the blood cell separation but also to sample disturbance by the dielectrophoretic force.

Discriminating hepatocellular carcinoma in rats using a high-Tc SQUID detected nuclear resonance spectrometer in a magnetic shielding box.

In this study, we report the spin-lattice relaxation rate of hepatocellular carcinoma (HCC) and normal liver tissue in rats using a high-T(c) superconducting quantum interference device (SQUID) based nuclear magnetic resonance (NMR) spectrometer. The resonance spectrometer used for discriminating liver tumors in rats via the difference in longitudinal relaxation time in low magnetic fields was set up in a compact and portable magnetic shielding box. The frequency-domain NMR signals of HCC tissues and normal liver tissues were analyzed to study their respective longitudinal relaxation rate T(1) (-1). The T(1) (-1) of liver tissues for ten normal rats and ten cancerous rats were investigated respectively. The averaged T(1) (-1) value of normal liver tissue was (6.41±0.66) s(-1), and the averaged T(1) (-1) value of cancerous tissue was (3.38±0.15) s(-1). The ratio of T(1) (-1) for normal liver tissues and cancerous liver tissues of the rats investigated is estimated to be 1.9. Since this significant statistical difference, the T(1) (-1) value can be used to distinguish the HCC tissues from normal liver tissues. This method of examining liver and tumor tissues has the advantages of being convenient, easy to operate, and stable.

A study of J-coupling spectroscopy using the Earth's field nuclear magnetic resonance inside a laboratory.

In this paper, an instrumentation of the Earth's field nuclear magnetic resonance (EFNMR) inside a laboratory is presented. A lock-in analysis (LIA) technique was proposed to enhance the signal-to-noise ratio (SNR). A SNR of 137.8 was achieved in a single measurement for 9 ml tap water, and the LIA technique significantly enhanced the SNR to 188 after a 10-average in a noisy laboratory environment. The proton-phosphorus coupling in trimethyl phosphate ((CH(3)O)(3)PO) with J-coupling J[H,F]=(10.99±0.013) Hz has been demonstrated. The LIA technique improves the SNR, and a 2.6-fold improvement in SNR over that of the frequency-adjusted averaging is achieved. To reduce the noise in EFNMR, it was suggested that the LIA technique and the first order gradient shim be used to achieve a subhertz linewidth.