Red Blood Cells' Area Deformation as the Origin of the Photoplethysmography Signal.

The origin of the photoplethysmography (PPG) signal is a debatable topic, despite plausible models being addressed. One concern revolves around the correlation between the mechanical waveform's pulsatile nature and the associated biomechanism. The interface between these domains requires a clear mathematical or physical model that can explain physiological behavior. Describing the correct origin of the recorded optical waveform not only benefits the development of the next generation of biosensors but also defines novel health markers. In this study, the assumption of a pulsatile nature is based on the mechanism of blood microcirculation. At this level, two interconnected phenomena occur: variation in blood flow velocity through the capillary network and red blood cell (RBC) shape deformation. The latter effect was qualitatively investigated in synthetic capillaries to assess the experimental data needed for PPG model development. Erythrocytes passed through 10 µm and 6 µm microchannel widths with imposed velocities between 50 µm/s and 2000 µm/s, according to real scenarios. As a result, the length and area deformation of RBCs followed a logarithmic law function of the achieved traveling speeds. Applying radiometric expertise on top, mechanical-optical insights are obtained regarding PPG's pulsatile nature. The mathematical equations derived from experimental data correlate microcirculation physiologic with waveform behavior at a high confidence level. The transfer function between the biomechanics and the optical signal is primarily influenced by the vasomotor state, capillary network orientation, concentration, and deformation performance of erythrocytes.

Field-Effect Transistors Based on Single-Layer Graphene and Graphene-Derived Materials.

The progress of advanced materials has invoked great interest in promising novel biosensing applications. Field-effect transistors (FETs) are excellent options for biosensing devices due to the variability of the utilized materials and the self-amplifying role of electrical signals. The focus on nanoelectronics and high-performance biosensors has also generated an increasing demand for easy fabrication methods, as well as for economical and revolutionary materials. One of the innovative materials used in biosensing applications is graphene, on account of its remarkable properties, such as high thermal and electrical conductivity, potent mechanical properties, and high surface area to immobilize the receptors in biosensors. Besides graphene, other competing graphene-derived materials (GDMs) have emerged in this field, with comparable properties and improved cost-efficiency and ease of fabrication. In this paper, a comparative experimental study is presented for the first time, for FETs having a channel fabricated from three different graphenic materials: single-layer graphene (SLG), graphene/graphite nanowalls (GNW), and bulk nanocrystalline graphite (bulk-NCG). The devices are investigated by scanning electron microscopy (SEM), Raman spectroscopy, and I-V measurements. An increased electrical conductance is observed for the bulk-NCG-based FET, despite its higher defect density, the channel displaying a transconductance of up to ≊4.9×10-3 A V-1, and a charge carrier mobility of ≊2.86×10-4 cm2 V-1 s-1, at a source-drain potential of 3 V. An improvement in sensitivity due to Au nanoparticle functionalization is also acknowledged, with an increase of the ON/OFF current ratio of over four times, from ≊178.95 to ≊746.43, for the bulk-NCG FETs.

Assessing Polysaccharides/Aloe Vera-Based Hydrogels for Tumor Spheroid Formation.

In vitro tumor spheroids have proven to be useful 3D tumor culture models for drug testing, and determining the molecular mechanism of tumor progression and cellular interactions. Therefore, there is a continuous search for their industrial scalability and routine preparation. Considering that hydrogels are promising systems that can favor the formation of tumor spheroids, our study aimed to investigate and develop less expensive and easy-to-use amorphous and crosslinked hydrogels, based on natural compounds such as sodium alginate (NaAlg), aloe vera (AV) gel powder, and chitosan (CS) for tumor spheroid formation. The ability of the developed hydrogels to be a potential spheroid-forming system was evaluated using MDA-MB-231 and U87MG cancer cells. Spheroid abilities were influenced by pH, viscosity, and crosslinking of the hydrogel. Addition of either AV or chitosan to sodium alginate increased the viscosity at pH 5, resulting in amorphous hydrogels with a strong gel texture, as shown by rheologic analysis. Only the chitosan-based gel allowed formation of spheroids at pH 5. Among the variants of AV-based amorphous hydrogels tested, only hydrogels at pH 12 and with low viscosity promoted the formation of spheroids. The crosslinked NaAlg/AV, NaAlg/AV/glucose, and NaAlg/CS hydrogel variants favored more efficient spheroid formation. Additional studies would be needed to use AV in other physical forms and other formulations of hydrogels, as the current study is an initiation, in evaluating the potential use of AV gel in tumor spheroid formation systems.

HT-29 Colon Cancer Cell Electromanipulation and Assessment Based on Their Electrical Properties.

This study proposes a feasible approach for the rapid, sensitive, and label-free identification of cancerous cells based on dielectrophoretic (DEP) manipulation and electrical characterization. In this method, the concentration of target cells at the level of customized microelectrodes via DEP is first determined, followed by an electrical impedance evaluation. The study demonstrates the capacity of the methodology to electrically differentiate HT-29 cancer cells from healthy blood cells based on their impedance spectra. Within a higher frequency domain, the electrical impedance of trapped cancer cells was significantly lower compared with the normal ones. In order to evaluate the functionality and reproducibility of the proposed method, the influence of the DEP and EIS (electrical impedance spectroscopy) operating voltages on the electrical characterization of trapped HT-29 cells was analyzed.

Vertical Graphene-Based Biosensor for Tumor Cell Dielectric Signature Evaluation.

The selective and rapid detection of tumor cells is of critical consequence for the theragnostic field of tumorigenesis; conventional methods, such as histopathological diagnostic methods, often require a long analysis time, excessive analytical costs, complex operations, qualified personnel and deliver many false-positive results. We are considering a new approach of an electrochemical biosensor based on graphene, which is evidenced to be a revolutionary nanomaterial enabling the specific and selective capture of tumor cells. In this paper, we report a biosensor fabricated by growing vertically aligned graphene nanosheets on the conductive surface of interdigitated electrodes which is functionalized with anti-EpCAM antibodies. The dielectric signature of the three types of tumor cells is determined by correlating the values from the Nyquist and Bode diagram: charge transfer resistance, electrical double layer capacity, Debye length, characteristic relaxation times of mobile charges, diffusion/adsorption coefficients, and variation in the electrical permittivity complex and of the phase shift with frequency. These characteristics are strongly dependent on the type of membrane molecules and the electromagnetic resonance frequency. We were able to use the fabricated sensor to differentiate between three types of tumor cell lines, HT-29, SW403 and MCF-7, by dielectric signature. The proposed evaluation method showed the permittivity at 1 MHz to be 3.63 nF for SW403 cells, 4.97 nF for HT 29 cells and 6.9 nF for MCF-7 cells.

New Amorphous Hydrogels with Proliferative Properties as Potential Tools in Wound Healing.

The study and discovery of bioactive compounds and new formulations as potential tools for promoting the repair of dermoepidermal tissue in wound healing is of continuing interest. We have developed a new formulation of amorphous hydrogel based on sodium alginate (NaAlg); type I collagen, isolated by the authors from silver carp tails (COL); glycerol (Gli); Aloe vera gel powder (AV); and silver nanoparticles obtained by green synthesis with aqueous Cinnamomum verum extract (AgNPs@CIN) and vitamin C, respectively. The gel texture of the amorphous hydrogels was achieved by the addition of Aloe vera, demonstrated by a rheological analysis. The evaluations of the cytotoxicity and cell proliferation capacity of the experimental amorphous hydrogels were performed against human foreskin fibroblast Hs27 cells (CRL-1634-ATCC). The developed gel formulations did not show a cytotoxic effect. The hydrogel variant containing AgNPs@CIN in a concentration of 8 µg Ag/gel formulation and hydrogel variant with vitamin C had proliferative activity. In addition, the antibacterial activity of the hydrogels was evaluated against S. aureus ATCC 6538, Ps. aeruginosa ATCC 27853, and E. coli ATCC 25922. The results demonstrated that the gel variant based on AgNPs@CIN in a concentration of 95 µg Ag/gel formulation and the hydrogel based on vitamin C show antibacterial activity. Therefore, the developed hydrogels with AgNPs@CIN and vitamin C could be promising alternatives in wound healing.

Investigation of Multiphase Flow in a Trifurcation Microchannel-A Benchmark Problem.

The evolution of an interface between two immiscible liquids in a three-branch symmetric microchannel is numerically and experimentally investigated. The main goals of the paper are to correlate the numeric data with the experimental results for the tested flow case and to assess the quality of the VOF procedure to trace the interface using the Fluent commercial code. The focus of the experiments was to characterize the dynamics of the oil-water interface formed in the vicinity of the bifurcation, at the entrance in the main microchannel of 400 microns width and 50 microns height. The oil core surrounded by water is visualized and micro-PIV measurements are performed in water. Experimental results qualitatively and quantitatively confirm the 3D numerical simulations. We propose the present investigated flow as a benchmark case for the study of the interface in a branching microchannel geometry.

Dielectrophoretic and Electrical Impedance Differentiation of Cancerous Cells Based on Biophysical Phenotype.

Here, we reported a study on the detection and electrical characterization of both cancer cell line and primary tumor cells. Dielectrophoresis (DEP) and electrical impedance spectroscopy (EIS) were jointly employed to enable the rapid and label-free differentiation of various cancer cells from normal ones. The primary tumor cells that were collected from two colorectal cancer patients, cancer cell lines (SW-403, Jurkat, and THP-1), and healthy peripheral blood mononuclear cells (PBMCs) were trapped first at the level of interdigitated microelectrodes with the help of dielectrophoresis. Correlation of the cells dielectric characteristics that was obtained via electrical impedance spectroscopy (EIS) allowed evident differentiation of the various types of cell. The differentiations were assigned to a "dielectric phenotype" based on their crossover frequencies. Finally, Randles equivalent circuit model was employed for highlighting the differences with regard to a series group of charge transport resistance and constant phase element for cancerous and normal cells.

Wound healing applications of creams and "smart" hydrogels.

Although superficial wounds are often easy to treat for healthy individuals, there are some more severe types of wounds (burns, ulcers, diabetic wounds, etc.) that are a challenge for clinicians. A good therapeutic result is based on the delivery of a treatment at the right time, for the right patient. Our goal was to sum up useful knowledge regarding wound healing and wound treatments, based on creams and hydrogels with various active ingredients. We concluded that both preparations have application in preventing infections and promoting healing, but their efficacy is clearly conditioned by the type, depth, severity of the wound and patient profile. However, due to their superior versatility and capability of maintaining the integrity and functionality of the active ingredient, as well as it is controlled release at site, hydrogels are more suited for incorporating different active ingredients. New wound healing devices can combine smart hydrogel dressings with physical therapies to deliver a more efficient treatment to patients if the indications are appropriate.

Low Field Optimization of a Non-Contacting High-Sensitivity GMR-Based DC/AC Current Sensor.

Many applications require galvanic isolation between the circuit where the current is flowing and the measurement device. While for AC, the current transformer is the method of choice, in DC and, especially for low currents, other sensing methods must be used. This paper aims to provide a practical method of improving the sensitivity and linearity of a giant magnetoresistance (GMR)-based current sensor by adapting a set of design rules and methods easy to be implemented. Our approach utilizes a multi-trace current trace and a double differential GMR based detection system. This essentially constitutes a planar coil which would effectively increase the usable magnetic field detected by the GMR sensor. An analytical model is developed for calculating the magnetic field generated by the current in the GMR sensing area which showed a significant increase in sensitivity up to 13 times compared with a single biased sensor. The experimental setup can measure both DC and AC currents between 2-300 mA, with a sensitivity between 15.62 to 23.19 mV/mA, for biasing fields between 4 to 8 Oe with a detection limit of 100 µA in DC and 100 to 300 µA in AC from 10 Hz to 50 kHz. Because of the double differential setup, the detection system has a high immunity to external magnetic fields and a temperature drift of the offset of about -2.59 × 10-4 A/°C. Finally, this setup was adapted for detection of magnetic nanoparticles (MNPs) which can be used to label biomolecules in lab-on-a-chip applications and preliminary results are reported.

The Impact of Internet Usage and Knowledge-Intensive Activities on Households' Healthcare Expenditures.

This paper examines the impact of the internet usage and knowledge intensive activities on households' healthcare expenditures Similarly, the paper aims to recognize and understand, from a value-creation perspective, the correlation between: internet access of households (IA), individuals frequently using the internet (IU), individuals searching on internet for health-related information (HI), payments made by households for healthcare (PHH), expressed as euro per inhabitant and employment in knowledge-intensive activities (KIA). The approach utilized in the present study consists of two steps. First, a theoretical framework was conducted to determine the existing relationship between major variables. Next, the Vector Autoregressive (VAR) approach was applied in a case study at European level to prove the three hypothesis we consider. By analyzing the connection between the major variables, a positive and long- lasting impulse response function was revealed, followed by an ascending trend. This suggests that a self-multiplying effect is being generated; and it reasonable to assume that the more individuals use the Internet, the more electronic acquisitions occur. We can thus reasonably conclude that the improvement of the internet usage and knowledge intensive activities on households' healthcare expenditures process is strongly dependent on people's capability. Improving IU and KIA is the new reading key in the decision-making process in health system approach.

Detection of Circulating Tumor Cells Using Microfluidics.

Metastasis is the main cause of death in cancer patients worldwide. During metastasis, cancer cells detach from the primary tumor and invade distant tissue. The cells that undergo this process are called circulating tumor cells (CTCs). Studies show that the number of CTCs in the peripheral blood can predict progression-free survival and overall survival and can be informative concerning the efficacy of treatment. Research is now concentrated on developing devices that can detect CTCs in the blood of cancer patients with improved sensitivity and specificity that can lead to improved clinical evaluation. This review focuses on devices that detect and capture CTCs using different cell properties (surface markers, size, deformability, electrical properties, etc.). We also discuss the process of tumor cell dissemination, the biology of CTCs, epithelial-mesenchymal transition (EMT), and several challenges and clinical applications of CTC detection.

A practical guide for the fabrication of microfluidic devices using glass and silicon.

This paper describes the main protocols that are used for fabricating microfluidic devices from glass and silicon. Methods for micropatterning glass and silicon are surveyed, and their limitations are discussed. Bonding methods that can be used for joining these materials are summarized and key process parameters are indicated. The paper also outlines techniques for forming electrical connections between microfluidic devices and external circuits. A framework is proposed for the synthesis of a complete glass/silicon device fabrication flow.