Enhancing signals of microfluidic impedance cytometry through optimization of microelectrode array.

Microfluidic impedance cytometry shows a great value in biomedical diagnosis. However, the crosstalk between neighboring microelectrodes strongly weakens the impedance signal. Hereby, we demonstrate a novel microfluidic impedance cytometer consisted of sensing electrodes and ground electrodes (GNDs). The simulation reveals a signal enhancement by more than five times with GNDs compared to that without ones. We also found that the linear correlation between the impedance at a high frequency and that at a low frequency varies as microparticle size changes, which can be used for microparticle classification. The study can help with microelectrode optimization and signal processing for microfluidic impedance analysis.

Evaluating the biological safety on mice at 16 T static magnetic field with 700 MHz radio-frequency electromagnetic field.

OBJECTIVES: This study evaluated the associated biological effects of radio-frequency (RF) exposure at 16 T magnetic resonance imaging (MRI) on mice health. MATERIAL AND METHODS: A total of 48 healthy 8-week-old male C57BL/6 mice were investigated. A 16 T high static magnetic field (HiSMF) was generated by a superconducting magnet, and a radiofrequency (RF) electromagnetic field for hydrogen resonance at 16 T (700 MHz) was transmitted via a homemade RF system. The mice were exposed inside the 16 T HiSMF with the 700 MHz RF field for 60 min, and the body weight, organ coefficients, histomorphology of major organs, and blood indices were analyzed for the basal state of the mice on day 0 and day 14. The Heat Shock Protein 70 (HSP70), cyclooxygenase 2 (COX2), and interleukin- 6 (IL-6) were used to evaluate the thermal effects on the brain. Locomotor activity, the open field test, tail suspension test, forced swimming test, and grip strength test were used to assess the behavioral characteristics of the mice. RESULTS: The 16 T HiSMF with 700 MHz RF electromagnetic field exposure had no significant effects on body weight, organ coefficients, or histomorphology of major organs in the mice. On day 0, the expressions of HSP70 and COX2 in the brain were increased by 16 T HiSMF with 700 MHz RF electromagnetic field exposure. However, the expression of HSP70, COX2, and IL-6 had no significant difference compared with the sham group on day 14. Compared with the sham groups, the meancorpuscularvolume (MCV) on day 0 and the total protein (TP) on day 14 were increased significantly, whereas the other blood indices did not change significantly. The 16 T HiSMF with 700 MHz RF electromagnetic field exposure caused the mice to briefly circle tightly but had no effect on other behavioral indicators. CONCLUSIONS: In summary, 16 T HiSMF with 700 MHz RF electromagnetic field exposure for 60 min did not have severe effects on mice.

[Development of Non-invasive Endoscope System with Magnetic Anchored Ablation Electrode for Early Cancer of Digestive Tract].

This study introduces a non-invasive gastrointestinal early cancer magnetic anchor ablation electrode endoscopy system, including a magnetic anchor module and ablation electrode module. The magnetic anchoring module is composed of an external guide magnet and an internal magnet, made of permanent magnet material NdFeB; the ablation electrode module is based on the modification of the front end lens hood of the existing endoscope (CMD-90D LED electronic upper gastrointestinal endoscope). The new endoscope system not only includes all the functions of the original endoscope, but also introduces magnetic anchoring to enable the ablation electrode to be accurately positioned and controllable in the process of treating tumors, avoiding the phenomenon of gastric perforation; the introduction of steep pulse electric field ablation electrodes realizes the purpose of non-invasive treatment. Its clinical application will become a new method to treat early cancer of the digestive tract.

Biological Effects of Hypomagnetic Field: Ground-Based Data for Space Exploration.

The future of mankind is tied to the exploration and eventual colonization of space. Currently, people have resided in orbit at a space station. In the future, we will have opportunities to stay on the moon, Mars, or in deeper space, where astronauts are exposed to the hypomagnetic field (HMF), which refers to an extremely weak magnetic field environment compared with the geomagnetic field. However, the potential risks of HMF exposure to human health are often overlooked. Here, we summarize the literature related to the biological effects of HMF and calculate the magnitude of the effect. Briefly, HMF impairs multiple animal systems, especially in the central nervous system. Additionally, HMF is a stress factor in plant growth and reproduction. Finally, HMF combined with other space environments, such as radiation and microgravity, can affect organisms. Further studies are required to explore (i) countermeasures to the adverse effects of HMF, (ii) combined effects of HMF with other factors, and (iii) the intensity-effect relationship. © 2021 Bioelectromagnetics Society.

A Robust Infrared Transducer of an Ultra-Large-Scale Array.

A robust micro-electro-mechanical systems (MEMS) infrared thin film transducer of an ultra-large-scale array was proposed and fabricated on a 4-inch silicon wafer. The silicon substrate and micro cavities were introduced. This novel transducer had excellent mechanical stability, time response, and state-of-the-art pixel scale. It could bear a load of 1700 g and its load pressure was improved by more than 5.24 times and time constant decreased by 50.7% compared to the traditional soft infrared thin film transducer. The array scale of its pixels exceeded 2k × 2k. The simulation and measured results of the transient temperature and radiation intensity were well consistent. Illuminated by a 532 nm laser with a frequency of 50 Hz and 50% duty cycle, the thermal decay time of the proposed transducer was 6.0 ms. A knife-edge image was utilized for spatial resolution test and the full width at half maximum (FWHM) of the proposed transducer was 24% smaller than the traditional soft one. High-resolution infrared images were generated using the proposed robust transducer. These results proved that the robust transducer was promising in infrared image generation.

Electrokinetic biomolecule preconcentration using xurography-based micro-nano-micro fluidic devices.

In this paper we introduce a low cost rapid prototyping framework for designing Micro-Nano-Micro (MNM) fluidic preconcentration device based on ion concentration polarization (ICP) phenomenon. Xurography-based microchannels are separated by a strip of ion perm-selective Nafion membrane which plays the role of nanofluidic potential barrier for the negatively charged molecules. As a result, by using this rapid and inexpensive fabrication technique, it is possible to get preconcentration plugs as high as 5000 fold with an original symmetric electroosmotic flow (EOF) condition. Due to its simplicity and performance, this device could be implemented in various bioanalysis systems.

The Influence of Electrode Design on Detecting the Effects of Ferric Ammonium Citrate (FAC) on Pre-Osteoblast through Electrical Cell-Substrate Impedance Sensing (ECIS).

Detection sensitivity is a crucial factor in the application of ECIS sensors. For these biosensors, the electrode configuration has a direct impact on sensitivity, yet few studies on monopolar electrodes have been reported. In this study, ECIS sensor arrays, which have a series of working electrode configuration with a wide diameter range and different electrode number, were fabricated to monitor living osteoblast-like MC3T3-E1 cells. The experimental results revealed that when the electrode diameter was larger than 25 µm, electrodes with smaller diameter and number yielded higher impedance values and generated more impedance shift to cell status change. The membrane capacitance obtained by equivalent circuit fitting was at the same level. When the electrode diameter was even smaller, the results in detection of cell monolayer were opposite, and there was no distinct relationship between impedance and membrane capacitance shift to cell status change and electrode geometry. The proposed sensor chip, allowing for a sustained and stable detection of cellular impedance, provides the basis for the selection of the electrode configuration of monopolar electrodes. The test results of electrodes with a diameter of 25 µm and lower indicated the possibility of single cell impedance measurement, which can provide unique insight into the heterogeneous electrical behavior of cells, and, in this case, the electrode size should be close to the cell size.

Biophysical mechanisms underlying the effects of static magnetic fields on biological systems.

With the widespread use of static magnetic fields (SMFs) in medicine, it is imperative to explore the biological effects of SMFs and the mechanisms underlying their effects on biological systems. The presence of magnetic materials within cells and organisms could affect various biological metabolism and processes, including stress responses, proliferation, and structural alignment. SMFs were generally found to be safe at the organ and organism levels. However. human subjects exposed to strong SMFs have reported side effects. In this review, we combined the magnetic properties of biological samples to illustrate the mechanism of action of SMFs on biological systems from a biophysical point of view. We suggest that the mechanisms of action of SMFs on biological systems mainly include the induction of electric fields and currents, generation of magnetic effects, and influence of electron spins. An electrolyte flowing in a static magnetic field generates an induced current and an electric field. Magnetomechanical effects include orientation effects upon subjecting biological samples to SMFs and movement of biological samples in strong field gradients. SMFs are thought to affect biochemical reaction rates and yields by influencing electron spin. This paper helps people how can harness the favorable biological effects of SMFs.

Epidermal Wearable Biosensors for Monitoring Biomarkers of Chronic Disease in Sweat.

Biological information detection technology is mainly used for the detection of physiological and biochemical parameters closely related to human tissues and organ lesions, such as biomarkers. This technology has important value in the clinical diagnosis and treatment of chronic diseases in their early stages. Wearable biosensors can be integrated with the Internet of Things and Big Data to realize the detection, transmission, storage, and comprehensive analysis of human physiological and biochemical information. This technology has extremely wide applications and considerable market prospects in frontier fields including personal health monitoring, chronic disease diagnosis and management, and home medical care. In this review, we systematically summarized the sweat biomarkers, introduced the sweat extraction and collection methods, and discussed the application and development of epidermal wearable biosensors for monitoring biomarkers in sweat in preclinical research in recent years. In addition, the current challenges and development prospects in this field were discussed.

Epidermal Wearable Biosensors for the Continuous Monitoring of Biomarkers of Chronic Disease in Interstitial Fluid.

Healthcare technology has allowed individuals to monitor and track various physiological and biological parameters. With the growing trend of the use of the internet of things and big data, wearable biosensors have shown great potential in gaining access to the human body, and providing additional functionality to analyze physiological and biochemical information, which has led to a better personalized and more efficient healthcare. In this review, we summarize the biomarkers in interstitial fluid, introduce and explain the extraction methods for interstitial fluid, and discuss the application of epidermal wearable biosensors for the continuous monitoring of markers in clinical biology. In addition, the current needs, development prospects and challenges are briefly discussed.

Ergonomic Consideration in Pillow Height Determinants and Evaluation.

(1) Background: Sleep problems have become one of the current serious public health issues. Pillow height affects the alignment of the cervical spine and is closely related to the mechanical environment of the cervical spine. An appropriate pillow height can provide adequate support for the head and neck to reduce the stress in the cervical spine and relax the muscles of the neck and shoulder, thereby relieving pain and improving sleep quality. (2) Methods: We reviewed the current trends, research methodologies, and determinants of pillow height evaluation, summarizing the evidences published since 1997. In particular, we scrutinized articles dealing with the physiological and mechanical characteristics of the head-neck-shoulder complex. (3) Results: Through the investigation and analysis of these articles, we presented several quantitative and objective determinants for pillow height evaluation, including cervical spine alignment, body dimension, contact pressure, and muscle activity. The measurement methods and selection criteria for these parameters are described in detail. However, the suggested range for achieving optimal cervical spine alignment, appropriate pressure distribution, and minimal muscle activity during sleep cannot yet be identified considering the lack of sufficient evidence. Moreover, there remain no firm conclusions about the optimal pillow height for the supine and lateral positions. (4) Conclusions: A comprehensive evaluation combining the above determinants provides a unique solution for ergonomic pillow design and proper pillow height selection, which can effectively promote the public sleep health. Therefore, it is necessary to develop a reasonable algorithm to weigh multiple determinants.

Programmable prodrug micelle with size-shrinkage and charge-reversal for chemotherapy-improved IDO immunotherapy.

IDO blockade-based immunotherapy has been impeded by the activation of antitumor immune response and low delivery efficiency of immunotherapeutic, resulting from natural biological barriers and immune resistance. Herein, a programmable drug delivery nanosystem with enhanced tumor penetration and endocytosis is constructed for chemotherapy-enhanced immunotherapy by loading immune checkpoint IDO inhibitor NLG919 in pH/redox cascade-responsive prodrug micelle. The nanosystem shrinked micelles sizes and converted charge from negative to positive for enhanced tumor penetration and endocytosis in responding to the weakly acidic tumor microenvironment. The endocytosed nanosystem dramatically disassembled and released curcumin and NLG919 in redox-rich cytoplasm. In vitro and in vivo studies demonstrate that the nanosystem not only effectively overcame biological barriers, but also significantly boosted antitumor immune response and reduced immune resistance. It was realized by the combined effects of chemotherapy-enhanced immunogenicity, and NLG919-induced IDO-blockade immunotherapy, consequently inhibiting tumor growth, metastasis and recurrence with high efficiency in vivo. The study offers a nanoplatform with deep tumor penetration, high cellular uptake and effective antitumor immune response for the advance of chemo-immunotherapy.

Combined Effects of Electric Stimulation and Microgrooves in Cardiac Tissue-on-a-Chip for Drug Screening.

Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip is made with facile lithographic and laser-cutting processes that can be easily scaled up to high-throughput format. The maturation and phenotypic changes of CMs cultured on the heart-on-a-chip is validated and it can be treated with various drugs to evaluate cardiotoxicity and cardioprotective efficacy. The heart-on-a-chip can provide a high-throughput drug screening platform in preclinical drug development.

Electrokinetic effect for molecular recognition: A label-free approach for real-time biosensing.

We present a simple and inexpensive method for label-free detection of biomolecules. The method monitors the changes in streaming current in a fused silica capillary as target biomolecules bind to immobilized receptors on the inner surface of the capillary. To validate the concept, we show detection and time response of different protein-ligand and protein-protein systems: biotin-avidin and biotin-streptavidin, barstar-dibarnase and Z domain-immunoglobulin G (IgG). We show that specific binding of these biomolecules can be reliably monitored using a very simple setup. Using sequential injections of various proteins at a diverse concentration range and as well as diluted human serum we further investigate the capacity of the proposed technique to perform specific target detection from a complex sample. We also investigate the time for the signal to reach equilibrium and its dependence on analyte concentration and demonstrate that the current setup can be used to detect biomolecules at a concentration as low as 100pM without requiring any advanced device fabrication procedures. Finally, an analytical model based on diffusion theory has been presented to explain the dependence of the saturation time on the analyte concentration and capillary dimensions and how reducing length and inner diameter of the capillary is predicted to give faster detection and in practice also lower limit of detection.

On the free-space Gaussian beam coupling to droplet optical resonators.

In this paper, light coupling into droplet optical resonators by means of a free-space Gaussian beam (GB) is investigated through numerical simulations and experiments. This method is introduced as an alternative to previously reported methods based on coupling through tapered fibers or prisms. Though applicable to solid-state optical resonators, this method is investigated here in the context of optofluidics for preserving the integrity of the droplet shape and for facilitating the steps of alignment and light coupling. The glycerol droplet under study is supported by a super-hydrophobic surface, which consists of Teflon-coated nanostructured silicon, to provide the advantage of keeping the droplet at a specific location, while maintaining a nearly spherical shape. The effectiveness of this method is tested with millimeter-sized droplets through measurements of their spectral responses. Quality factors Q in excess of 6 × 10(3) have been recorded. An analytical model for the external quality factor associated with this coupling technique has been derived, and the effect of the coupling parameters is demonstrated, allowing discussion about the scaling effects.