Improving the Efficacy of Magnetic Nanoparticle-Mediated Hyperthermia Using Trapezoidal Pulsed Electromagnetic Fields as an In Vitro Anticancer Treatment in Melanoma and Glioblastoma Multiforme Cell Lines.

Magnetic hyperthermia (MHT) is an oncological therapy that uses magnetic nanoparticles (MNPs) to generate localized heat under a low-frequency alternating magnetic field (AMF). Recently, trapezoidal pulsed alternating magnetic fields (TPAMFs) have proven their efficacy in enhancing the efficiency of heating in MHT as compared to the sinusoidal one. Our study aims to compare the TPAMF waveform's killing effect against the sinusoidal waveform in B16F10 and CT2A cell lines to determine more efficient waveforms in causing cell death. For that purpose, we used MNPs and different AMF waveforms: trapezoidal (TP), almost-square (TS), triangular (TR), and sinusoidal signal (SN). MNPs at 1 and 4 mg/mL did not affect cell viability during treatment. The exposition of B16F10 and CT2A cells to only AMF showed nonsignificant mortality. Hence, the synergetic effect of the AMF and MNPs causes the observed cell death. Among the explored cases, the nonharmonic signals demonstrated better efficacy than the SN one as an MHT treatment. This study has revealed that the application of TP, TS, or TR waveforms is more efficient and has considerable capability to increase cancer cell death compared to the traditional sinusoidal treatment. Overall, we can conclude that the application of nonharmonic signals enhances MHT treatment efficiency against tumor cells.

ANN-Based Discernment of Septic and Inflammatory Synovial Fluid: A Novel Method Using Viscosity Data from a QCR Sensor.

The synovial fluid (SF) analysis involves a series of chemical and physical studies that allow opportune diagnosing of septic, inflammatory, non-inflammatory, and other pathologies in joints. Among the variety of analyses to be performed on the synovial fluid, the study of viscosity can help distinguish between these conditions, since this property is affected in pathological cases. The problem with viscosity measurement is that it usually requires a large sample volume, or the necessary instrumentation is bulky and expensive. This study compares the viscosity of normal synovial fluid samples with samples with infectious and inflammatory pathologies and classifies them using an ANN (Artificial Neural Network). For this purpose, a low-cost, portable QCR-based sensor (10 MHz) was used to measure the viscous responses of the samples by obtaining three parameters: Δf, ΔΓ (parameters associated with the viscoelastic properties of the fluid), and viscosity calculation. These values were used to train the algorithm. Different versions of the ANN were compared, along with other models, such as SVM and random forest. Thirty-three samples of SF were analyzed. Our study suggests that the viscosity characterized by our sensor can help distinguish infectious synovial fluid, and that implementation of ANN improves the accuracy of synovial fluid classification.

Portable Quartz Crystal Resonator Sensor for Characterising the Gelation Kinetics and Viscoelastic Properties of Hydrogels.

Hydrogel biomaterials have found use in various biomedical applications partly due to their biocompatibility and tuneable viscoelastic properties. The ideal rheological properties of hydrogels depend highly on the application and should be considered early in the design process. Rheometry is the most common method to study the viscoelastic properties of hydrogels. However, rheometers occupy much space and are costly instruments. On the other hand, quartz crystal resonators (QCRs) are devices that can be used as low-cost, small, and accurate sensors to measure the viscoelastic properties of fluids. For this reason, we explore the capabilities of a low-cost and compact QCR sensor to sense and characterise the gelation process of hydrogels while using a low sample amount and by sensing two different crosslink reactions: covalent bonds and divalent ions. The gelation of covalently crosslinked mucin hydrogels and physically crosslinked alginate hydrogels could be monitored using the sensor, clearly distinguishing the effect of several parameters affecting the viscoelastic properties of hydrogels, including crosslinking chemistry, polymer concentrations, and crosslinker concentrations. QCR sensors offer an economical and portable alternative method to characterise changes in a hydrogel material's viscous properties to contribute to this type of material design, thus providing a novel approach.

Effects of sliding window variation in the performance of acceleration-based human activity recognition using deep learning models.

Deep learning (DL) models are very useful for human activity recognition (HAR); these methods present better accuracy for HAR when compared to traditional, among other advantages. DL learns from unlabeled data and extracts features from raw data, as for the case of time-series acceleration. Sliding windows is a feature extraction technique. When used for preprocessing time-series data, it provides an improvement in accuracy, latency, and cost of processing. The time and cost of preprocessing can be beneficial especially if the window size is small, but how small can this window be to keep good accuracy? The objective of this research was to analyze the performance of four DL models: a simple deep neural network (DNN); a convolutional neural network (CNN); a long short-term memory network (LSTM); and a hybrid model (CNN-LSTM), when variating the sliding window size using fixed overlapped windows to identify an optimal window size for HAR. We compare the effects in two acceleration sources': wearable inertial measurement unit sensors (IMU) and motion caption systems (MOCAP). Moreover, short sliding windows of sizes 5, 10, 15, 20, and 25 frames to long ones of sizes 50, 75, 100, and 200 frames were compared. The models were fed using raw acceleration data acquired in experimental conditions for three activities: walking, sit-to-stand, and squatting. Results show that the most optimal window is from 20-25 frames (0.20-0.25s) for both sources, providing an accuracy of 99,07% and F1-score of 87,08% in the (CNN-LSTM) using the wearable sensors data, and accuracy of 98,8% and F1-score of 82,80% using MOCAP data; similar accurate results were obtained with the LSTM model. There is almost no difference in accuracy in larger frames (100, 200). However, smaller windows present a decrease in the F1-score. In regard to inference time, data with a sliding window of 20 frames can be preprocessed around 4x (LSTM) and 2x (CNN-LSTM) times faster than data using 100 frames.

Enhancing Magnetic Hyperthermia Nanoparticle Heating Efficiency with Non-Sinusoidal Alternating Magnetic Field Waveforms.

For decades now, conventional sinusoidal signals have been exclusively used in magnetic hyperthermia as the only alternating magnetic field waveform to excite magnetic nanoparticles. However, there are no theoretical nor experimental reasons that prevent the use of different waveforms. The only justifiable motive behind using the sinusoidal signal is its availability and the facility to produce it. Following the development of a configurable alternating magnetic field generator, we aim to study the effect of various waveforms on the heat production effectiveness of magnetic nanoparticles, seeking to prove that signals with more significant slope values, such as the trapezoidal and almost-square signals, allow the nanoparticles to reach higher efficiency in heat generation. Furthermore, we seek to point out that the nanoparticle power dissipation is dependent on the waveform's slope and not only the frequency, magnetic field intensity and the nanoparticle size. The experimental results showed a remarkably higher heat production performance of the nanoparticles when exposed to trapezoidal and almost-square signals than conventional sinusoidal signals. We conclude that the nanoparticles respond better to the trapezoidal and almost-square signals. On the other hand, the experimental results were used to calculate the normalized power dissipation value and prove its dependency on the slope. However, adjustments are necessary to the coil before proceeding with in vitro and in vivo studies to handle the magnetic fields required.

Inertial Measurement Unit Sensors in Assistive Technologies for Visually Impaired People, a Review.

A diverse array of assistive technologies have been developed to help Visually Impaired People (VIP) face many basic daily autonomy challenges. Inertial measurement unit sensors, on the other hand, have been used for navigation, guidance, and localization but especially for full body motion tracking due to their low cost and miniaturization, which have allowed the estimation of kinematic parameters and biomechanical analysis for different field of applications. The aim of this work was to present a comprehensive approach of assistive technologies for VIP that include inertial sensors as input, producing results on the comprehension of technical characteristics of the inertial sensors, the methodologies applied, and their specific role in each developed system. The results show that there are just a few inertial sensor-based systems. However, these sensors provide essential information when combined with optical sensors and radio signals for navigation and special application fields. The discussion includes new avenues of research, missing elements, and usability analysis, since a limitation evidenced in the selected articles is the lack of user-centered designs. Finally, regarding application fields, it has been highlighted that a gap exists in the literature regarding aids for rehabilitation and biomechanical analysis of VIP. Most of the findings are focused on navigation and obstacle detection, and this should be considered for future applications.

Viscosity Measurement Sensor: A Prototype for a Novel Medical Diagnostic Method Based on Quartz Crystal Resonator.

Viscosity variation in human fluids, such as Synovial Fluid (SF) or Cerebrospinal Fluid (CSF), can be used as a diagnostic factor; however, the sample volume obtained for analysis is usually small, making it difficult to measure its viscosity. On the other hand, Quartz Crystal Resonators (QCR) have been used widely in sensing applications due to their accuracy, cost, and size. This work provides the design and validation of a new viscosity measurement system based on quartz crystal resonators for low volume fluids, leading to the development of a sensor called "ViSQCT" as a prototype for a new medical diagnostic tool. The proposed method is based on measuring the resonance frequency at the crystal's maximum conductance point through a frequency sweep, where crystals with 10 MHz fundamental resonance frequency were used. For validation purposes, artificial fluids were developed to simulate SFs and CFs in healthy and pathological conditions as experiment phantoms. A commercial QCR based system was also used for validation since its methodology differs from ours. A conventional rotational viscometer was used as a reference for calibration purposes. ViSQCT demonstrates the capability to measure the sample's viscosity differentiation between healthy and pathological fluid phantoms and shows that it can be used as a basis for a diagnostic method of several pathologies related to the studied biological fluids. However, some performance differences between both QCR-based systems compared to the reference system deserves further investigation.

Slowdown intracranial glioma progression by optical hyperthermia therapy: study on a CT-2A mouse astrocytoma model.

Metallic nanorods are promising agents for a wide range of biomedical applications. We report an optical hyperthermia method capable of inducing slowdown tumor progression of an experimental in vivo CT-2A glioblastoma tumor. The tumor model used in this research is based on the transplantation of mouse astrocytoma CT-2A cells in the striatum of mice by intracranial stereotaxic surgery. Two weeks after cell implant, the resulting tumor is treated by irradiating intratumoral injected gold nanorods, biofunctionalized with CD133 antibody (B-GNRs), using a continuous wave laser. Nanoparticles convert the absorbed light into localized heat (reaching up to 44 °C) due to the effect of surface plasmon resonance. A significant slowdown in CT-2A tumor progression is evident, by histology and magnetic resonance imaging, at one (p = 0.03) and two weeks (p = 0.008) after irradiation treatment. A notable deceleration in tumor size (15%-75%) as compared to the control untreated groups, it is observed. Thus, laser irradiation of B-GNRs is found to be effective for the treatment of CT-2A tumor progression. Similarities between the pre-clinical CT-2A tumor model and the human astrocytoma disease, in terms of anatomy, metastatic behavior and histopathology, suggest that hyperthermic treatment by laser irradiation of B-GNRs administered into high-grade human astrocytoma might constitute a promising alternative treatment to limit the progression of this deadly disease.

Influence of medium viscosity and intracellular environment on the magnetization of superparamagnetic nanoparticles in silk fibroin solutions and 3T3 mouse fibroblast cell cultures.

Biomedical applications based on the magnetic properties of superparamagnetic iron oxide nanoparticles (SPIONs) may be altered by the mechanical attachment or cellular uptake of these nanoparticles. When nanoparticles interact with living cells, they are captured and internalized into intracellular compartments. Consequently, the magnetic behavior of the nanoparticles is modified. In this paper, we investigated the change in the magnetic response of 14 nm magnetic nanoparticles (Fe3O4) in different solutions, both as a stable liquid suspension (one of them mimicking the cellular cytoplasm) and when associated with cells. The field-dependent magnetization curves from inert fluids and cell cultures were determined by using an alternating gradient magnetometer, MicroMagTM 2900. The equipment was adapted to measure liquid samples because it was originally designed only for solids. In order to achieve this goal, custom sample holders were manufactured. Likewise, the nuclear magnetic relaxation dispersion profiles for the inert fluid were also measured by fast field cycling nuclear magnetic relaxation relaxometry. The results show that SPION magnetization in inert fluids was affected by the carrier liquid viscosity and the concentration. In cell cultures, the mechanical attachment or confinement of the SPIONs inside the cells accounted for the change in the dynamic magnetic behavior of the nanoparticles. Nevertheless, the magnetization value in the cell cultures was slightly lower than that of the fluid simulating the viscosity of cytoplasm, suggesting that magnetization loss was not only due to medium viscosity but also to a reduction in the mechanical degrees of freedom of SPIONs rotation and translation inside cells. The findings presented here provide information on the loss of magnetic properties when nanoparticles are suspended in viscous fluids or internalized in cells. This information could be exploited to improve biomedical applications based on magnetic properties such as magnetic hyperthermia, contrast agents and drug delivery.

Photoacoustic effect measurement in aqueous suspensions of gold nanorods caused by low-frequency and low-power near-infrared pulsing laser irradiation.

When aqueous suspensions of gold nanorods are irradiated with a pulsing laser (808 nm), pressure waves appear even at low frequencies (pulse repetition rate of 25 kHz). We found that the pressure wave amplitude depends on the dynamics of the phenomenon. For fixed concentration and average laser current intensity, the amplitude of the pressure waves shows a trend of increasing with the pulse slope and the pulse maximum amplitude. We postulate that the detected ultrasonic pressure waves are a sort of shock waves that would be generated at the beginning of each pulse, because the pressure wave amplitude would be the result of the positive interference of all the individual shock waves.

Induction of cell death in a glioblastoma line by hyperthermic therapy based on gold nanorods.

BACKGROUND: Metallic nanorods are promising agents for a wide range of biomedical applications. In this study, we developed an optical hyperthermia method capable of inducing in vitro death of glioblastoma cells. METHODS: The procedure used was based on irradiation of gold nanorods with a continuous wave laser. This kind of nanoparticle converts absorbed light into localized heat within a short period of time due to the surface plasmon resonance effect. The effectiveness of the method was determined by measuring changes in cell viability after laser irradiation of glioblastoma cells in the presence of gold nanorods. RESULTS: Laser irradiation in the presence of gold nanorods induced a significant decrease in cell viability, while no decrease in cell viability was observed with laser irradiation or incubation with gold nanorods alone. The mechanism of cell death mediated by gold nanorods during photothermal ablation was analyzed, indicating that treatment compromised the integrity of the cell membrane instead of initiating the process of programmed cell death. CONCLUSION: The use of gold nanorods in hyperthermal therapies is very effective in eliminating glioblastoma cells, and therefore represents an important area of research for therapeutic development.