Membrane-based microfluidic systems for medical and biological applications.

Microfluidic devices with integrated membranes that enable control of mass transport in constrained environments have shown considerable growth over the last decade. Membranes are a key component in several industrial processes such as chemical, pharmaceutical, biotechnological, food, and metallurgy separation processes as well as waste management applications, allowing for modular and compact systems. Moreover, the miniaturization of a process through microfluidic devices leads to process intensification together with reagents, waste and cost reduction, and energy and space savings. The combination of membrane technology and microfluidic devices allows therefore magnification of their respective advantages, providing more valuable solutions not only for industrial processes but also for reproducing biological processes. This review focuses on membrane-based microfluidic devices for biomedical science with an emphasis on microfluidic artificial organs and organs-on-chip. We provide the basic concepts of membrane technology and the laws governing mass transport. The role of the membrane in biomedical microfluidic devices, along with the required properties, available materials, and current challenges are summarized. We believe that the present review may be a starting point and a resource for researchers who aim to replicate a biological phenomenon on-chip by applying membrane technology, for moving forward the biomedical applications.

Edible Bite Force Sensor: A Novel Approach to Measuring Bite Force in Biomedical and Dental Applications.

BACKGROUND Measurement of bite force plays a crucial role in assessment of the masticatory system. With a growing interest in detecting occlusal irregularities, bite force sensors have garnered attention in the biomedical field. This study aimed to introduce a hydrogel bite force sensor, based on hydroxyethyl-cellulose-fructose-water (HEC-F-water), for premolar and molar teeth, and to evaluate it using optical profilometry, infrared spectroscopy (FTIR), and Instron Tension testing system, with 2.5 cm (1 inch) margins at top, bottom, right, and left. MATERIAL AND METHODS We fabricated 20 HEC-F-water hydrogel samples sized with surface of 1×1 cm, with 2 different widths - 1 mm and 5 mm. The samples were characterized using optical profilometry and FTIR and their electrical characteristics were determined using an impedance analyzer. Aluminum (Al) electrodes, fabricated using Cutting Plotter, were used to form a HEC-F-water-based transducer, which was used for bite force sensing. The Instron tensile testing system was employed, utilizing 3D printed models of the upper and lower jaw, to simulate biting. Forces in the range between 40 N and 540 N were exerted upon the transducer, and the output change in the electrical signal was measured. RESULTS The study determined the transfer function between bite force and capacitance. The fabricated sensor exhibited a sensitivity of 3.98 pF/N, an input range of 500 N, output range of 2 nF, and accuracy of 95.9%. CONCLUSIONS This study introduces an edible bite force sensor employing an edible hydrogel as a dielectric, presenting a novel avenue in the development of edible sensorics in dentistry.

A fully textile-based, tunable, force and strain sensing resistor for e-textile applications.

This work presents a novel approach towards integrating electronic components with textiles, by successfully creating a fully textile-based element that is capable of detecting applied forces by variation in its resistance value. The fabrication of the device consists of a specialized siliconized conductive fabric, which is placed above and below a layer of switch fabric, which acts as a force sensor. In this paper, the effects of three different geometries are observed, as well as the washability of the device, along with tension testing. Μoreover, the device behavior is simulated as well as applied in a real-life scenario. The proposed element demonstrates a good dynamic range, high repeatability and stability, and minimal impact of washing, creating a great candidate for integration in e-textiles.

Fabrication of Bilayer Nanofibrous-Hydrogel Scaffold from Bacterial Cellulose, PVA, and Gelatin as Advanced Dressing for Wound Healing and Soft Tissue Engineering.

Tissue engineering is currently one of the fastest-growing areas of engineering, requiring the fabrication of advanced and multifunctional materials that can be used as scaffolds or dressings for tissue regeneration. In this work, we report a bilayer material prepared by electrospinning a hybrid material of poly(vinyl alcohol) (PVA) and bacterial cellulose (BC NFs) (top layer) over a highly interconnected porous 3D gelatin-PVA hydrogel obtained by a freeze-drying process (bottom layer). The techniques were combined to produce an advanced material with synergistic effects on the physical and biological properties of the two materials. The bilayer material was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a water contact measurement system (WCMS). Studies on swelling, degradability, porosity, drug release, cellular and antibacterial activities were performed using standardized procedures and assays. FTIR confirmed cross-linking of both the top and bottom layers, and SEM showed porous structure for the bottom layer, random deposition of NFs on the surface, and aligned NFs in the cross section. The water contact angle (WCA) showed a hydrophilic surface for the bilayer material. Swelling analysis showed high swelling, and degradation analysis showed good stability. The bilayer material released Ag-sulfadiazine in a sustained and controlled manner and showed good antibacterial activities against severe disease-causing gram + ive and -ive (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) bacterial strains. In vitro biological studies were performed on fibroblasts (3T3) and human embryonic kidneys (HEK-293), which showed desirable cell viability, proliferation, and adhesion to the bilayer. Thus, the synergistic effect of NFs and the hydrogel resulted in a potential wound dressing material for wound healing and soft tissue engineering.

Fundamental properties of smart hydrogels for tissue engineering applications: A review.

Tissue engineering is an advanced and potential biomedical approach to treat patients suffering from lost or failed an organ or tissue to repair and regenerate damaged tissues that increase life expectancy. The biopolymers have been used to fabricate smart hydrogels to repair damaged tissue as they imitate the extracellular matrix (ECM) with intricate structural and functional characteristics. These hydrogels offer desired and controllable qualities, such as tunable mechanical stiffness and strength, inherent adaptability and biocompatibility, swellability, and biodegradability, all crucial for tissue engineering. Smart hydrogels provide a superior cellular environment for tissue engineering, enabling the generation of cutting-edge synthetic tissues due to their special qualities, such as stimuli sensitivity and reactivity. Numerous review articles have presented the exceptional potential of hydrogels for various biomedical applications, including drug delivery, regenerative medicine, and tissue engineering. Still, it is essential to write a comprehensive review article on smart hydrogels that successfully addresses the essential challenging issues in tissue engineering. Hence, the recent development on smart hydrogel for state-of-the-art tissue engineering conferred progress, highlighting significant challenges and future perspectives. This review discusses recent advances in smart hydrogels fabricated from biological macromolecules and their use for advanced tissue engineering. It also provides critical insight, emphasizing future research directions and progress in tissue engineering.

Oral micro-electronic platform for temperature and humidity monitoring.

Intraoral theranostics, the integration of diagnostics and therapeutics within the oral cavity, is gaining significant traction. This pioneering approach primarily addresses issues like xerostomia (dry mouth), commonly resulting from cancer treatment, with a specific focus on monitoring temperature and humidity. This paper introduces the innovative Intra-Oral Portable Micro-Electronic (IOPM) fluidic theranostic device platform. It leverages conventional dental spoons by incorporating advanced sensors for precise measurements of oral temperature and humidity. Personalization options include a microfluidic chip and a tooth model, enabling targeted delivery of therapeutic agents to optimize treatment outcomes. The electronic control system simplifies the administration of fluid dosages, intelligently adjusted based on real-time oral cavity temperature and humidity readings. Rigorous experimental evaluations validate the platform's precision in delivering fluid volumes at predefined intervals. This platform represents a transformative advancement for individuals contending with oral health challenges such as xerostomia (dry mouth). Furthermore, it has the potential to elevate oral healthcare standards by providing advanced diagnostics and tailored therapeutic solutions, benefiting both patients and dental professionals alike.

Toothpaste ingestion-evaluating the problem and ensuring safety: systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the ingestion of toothpaste and its sequelae. The study adhered to the PRISMA guidelines and was registered in the PROSPERO database. A comprehensive search strategy was conducted across multiple databases, resulting in the inclusion of 18 relevant publications. Eligible studies encompassed various designs and included both children and adults as the study population. Data extraction was carried out systematically, and relevant information on study characteristics, interventions, and outcomes were collected. The assessment of bias was performed using the Joanna Briggs Institute's Critical Appraisal Tools showing variations of bias among the included studies. The overall risk of systemic toxicity was found to be low, and no severe or life-threatening events were reported in the included studies. Furthermore, some toothpaste formulations containing higher concentrations of fluoride were associated with an increased risk of dental fluorosis. These findings have several implications for practice and policy. Healthcare providers and dental professionals should emphasize the importance of promoting safe toothpaste use, especially in vulnerable populations such as young children who are more prone to accidental ingestion. Public health campaigns and educational initiatives should aim to raise awareness about appropriate toothpaste usage and the potential risks. In addition, toothpaste manufacturers and regulatory bodies should consider revising guidelines and regulations to ensure the safety of oral care products, including the appropriate concentration of active ingredients. Future research should focus on investigating the long-term effects of toothpaste ingestion, exploring potential interactions between different active ingredients, and evaluating the efficacy of current preventive measures.

Graphene Oxide-Functionalized Bacterial Cellulose-Gelatin Hydrogel with Curcumin Release and Kinetics: In Vitro Biological Evaluation.

Biopolymer-based bioactive hydrogels are excellent wound dressing materials for wound healing applications. They have excellent properties, including hydrophilicity, tunable mechanical and morphological properties, controllable functionality, biodegradability, and desirable biocompatibility. The bioactive hydrogels were fabricated from bacterial cellulose (BC), gelatin, and graphene oxide (GO). The GO-functionalized-BC (GO-f-BC) was synthesized by a hydrothermal method and chemically crosslinked with bacterial cellulose and gelatin using tetraethyl orthosilicate (TEOS) as a crosslinker. The structural, morphological, and wettability properties were studied using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a universal testing machine (UTM), respectively. The swelling analysis was conducted in different media, and aqueous medium exhibited maximum hydrogel swelling compared to other media. The Franz diffusion method was used to study curcumin (Cur) release (Max = 69.32%, Min = 49.32%), and Cur release kinetics followed the Hixson-Crowell model. Fibroblast (3T3) cell lines were employed to determine the cell viability and proliferation to bioactive hydrogels. Antibacterial activities of bioactive hydrogels were evaluated against infection-causing bacterial strains. Bioactive hydrogels are hemocompatible due to their less than 0.5% hemolysis against fresh human blood. The results show that bioactive hydrogels can be potential wound dressing materials for wound healing applications.

Role of Graphene Oxide in Bacterial Cellulose-Gelatin Hydrogels for Wound Dressing Applications.

Biopolymer-based hydrogels have several advantages, including robust mechanical tunability, high biocompatibility, and excellent optical properties. These hydrogels can be ideal wound dressing materials and advantageous to repair and regenerate skin wounds. In this work, we prepared composite hydrogels by blending gelatin and graphene oxide-functionalized bacterial cellulose (GO-f-BC) with tetraethyl orthosilicate (TEOS). The hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscope (AFM), and water contact angle analyses to explore functional groups and their interactions, surface morphology, and wetting behavior, respectively. The swelling, biodegradation, and water retention were tested to respond to the biofluid. Maximum swelling was exhibited by GBG-1 (0.01 mg GO amount) in all media (aqueous = 1902.83%, PBS = 1546.63%, and electrolyte = 1367.32%). All hydrogels were hemocompatible, as their hemolysis was less than 0.5%, and blood coagulation time decreased as the hydrogel concentration and GO amount increased under in vitro standard conditions. These hydrogels exhibited unusual antimicrobial activities against Gram-positive and Gram-negative bacterial strains. The cell viability and proliferation were increased with an increased GO amount, and maximum values were found for GBG-4 (0.04 mg GO amount) against fibroblast (3T3) cell lines. The mature and well-adhered cell morphology of 3T3 cells was found for all hydrogel samples. Based on all findings, these hydrogels would be a potential wound dressing skin material for wound healing applications.

Paper card-like electrochemical platform as a smart point-of-care device for reagent-free glucose measurement in tears.

This communication describes the development of polyvinyl chloride electrochemical system in which a paper layer loaded with reagents is inserted into the device, demonstrating a new concept of a paper card-like pad for a reagent-free and easy measurement of the target analyte in solution. This device detects glucose in artificial tears in the range of 0.2-2 mM with a detection limit of 50 µM by simply adding the artificial tears to the paper card-like pad. The novel configuration goes beyond the state of the art, widening the application range of paper in the design of smart analytical devices.

A novel method for in-situ extracting bio-impedance model parameters optimized for embedded hardware.

A novel method for embedded hardware-based parameter estimation of the Cole model of bioimpedance is developed and presented. The model parameters R∞, R1 and C are estimated using the derived set of equations based on measured values of real (R) and imaginary part (X) of bioimpedance, as well as the numerical approximation of the first derivative of quotient R/X with respect to angular frequency. The optimal value for parameter α is estimated using a brute force method. The estimation accuracy of the proposed method is very similar with the relevant work from the existing literature. Moreover, performance evaluation was performed using the MATLAB software installed on a laptop, as well as on the three embedded-hardware platforms (Arduino Mega2560, Raspberry Pi Pico and XIAO SAMD21). Obtained results showed that the used platforms can perform reliable bioimpedance processing with the same accuracy, while Raspberry Pi Pico is the fastest solution with the smallest energy consumption.

A novel microfluidic compact disc to investigate electrochemical property changes between artificial and real salivary samples mixed with mouthwashes using electrical impedance analysis.

Diagnosing oral diseases at an early stage may lead to better preventive treatments, thus reducing treatment burden and costs. This paper introduces a systematic design of a microfluidic compact disc (CD) consisting of six unique chambers that run simultaneously from sample loading, holding, mixing and analysis. In this study, the electrochemical property changes between real saliva and artificial saliva mixed with three different types of mouthwashes (i.e. chlorhexidine-, fluoride- and essential oil (Listerine)-based mouthwashes) were investigated using electrical impedance analysis. Given the diversity and complexity of patient's salivary samples, we investigated the electrochemical impedance property of healthy real saliva mixed with different types of mouthwashes to understand the different electrochemical property which could be a foundation for diagnosis and monitoring of oral diseases. On the other hand, electrochemical impedance property of artificial saliva, a commonly used moisturizing agent and lubricant for the treatment of xerostomia or dry mouth syndrome was also studied. The findings indicate that artificial saliva and fluoride-based mouthwash showed higher conductance values compared to real saliva and two other different types of mouthwashes. The ability of our new microfluidic CD platform to perform multiplex processes and detection of electrochemical property of different types of saliva and mouthwashes is a fundamental concept for future research on salivary theranostics using point-of-care microfluidic CD platform.

Wearable humidity sensor embroidered on a commercial face mask and its electrical properties.

Owing to the rapid development in the field of e-textile-based flexible and portable sensors, the present work demonstrates a fully textile-based stretchable face mask humidity sensor which was created using digital embroidery technique. The design of the sensor was comprised of interdigitated structured electrodes made up of polymer core-based conductive silver-coated threads and hygroscopic threads embedded between them. The fabricated sensor performed well towards moisture detection in accordance with the principle where resistance of the face mask sensor decreased with the increase in the relative humidity along with the changing operational frequency in the range from 1 Hz to 200 kHz. The electrical response (resistance, impedance, capacitance and phase angle) of the novel thread-based sensor towards change in relative humidity was recorded and showed in the present work. The embroidery of polymer-based threads onto the face mask towards humidity sensing offers a novel wearable platform for more extended biomedical applications for detection of various breath biomarkers and thus early diagnosis of diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s10853-022-08135-2.

Polymer-Thread-Based Fully Textile Capacitive Sensor Embroidered on a Protective Face Mask for Humidity Detection.

The COVID-19 pandemic has created a situation where wearing personal protective masks is a must for every human being and introduced them as a part of everyday life. This work demonstrates a new functionality embedded in single-use face masks through an embroidered humidity sensor. The design of the face mask humidity sensor is comprised of interdigitated electrodes made of polyamide-based conductive threads and common polyester threads which act as a dielectric sensing layer embroidered between them. Therefore, the embroidered sensor acts as a capacitor, the performance of which was studied in increasing humidity conditions in the frequency range from 1 Hz to 100 kHz. The moisture adsorbed by sensitive hygroscopic polyester threads altered their dielectric and permittivity properties which were detected by the change in capacitance values of the face mask sensors at different relative humidity (RH) levels. The calculated limit of detection (LOD) values for the two proposed sensors at different frequencies (1, 10, and 100 kHz) were found in the range from 11.46% RH-27.41% RH and 29.79% RH-38.65% RH. The tested sensors showed good repeatability and stability under different humidity conditions over a period of 80 min. By employing direct embroidery of silver-coated polyamide conductive threads and moisture-sensitive polyester threads onto the face mask, the present work exploits the application of polymer-based textile materials in developing novel stretchable sensing devices toward e-textile applications.

Nanotopography Evaluation of NiTi Alloy Exposed to Artificial Saliva and Different Mouthwashes.

Nitinol (NiTi) alloy is a widely used material for the production of orthodontic archwires. Its corrosion behavior in conditions that exist in the oral cavity still remains a great characterization challenge. The motivation behind this work is to reveal the influence of commercially available mouthwashes on NiTi orthodontic archwires by performing non-electrochemical corrosion tests and quantifying the changes in the nanotopography of commercially available NiTi orthodontic wires. In this study, we examined the behavior of NiTi alloy archwires exposed for 21.5 days to different corrosive media: artificial saliva, Eludril®, Aquafresh®, and Listerine®. The corrosion was characterized by contact mode atomic force microscopy (AFM) before and after the corrosion tests. A novel analysis methodology was developed to obtain insight into locations of material gain or material loss based on standard surface roughness parameters Sa, Sdr, Ssk, and S10z. The developed methodology revealed that fluoride-containing mouthwashes (Aquafresh® and Listerine®) dominantly cause material loss, while chloride-containing mouthwash (Eludril®) can cause both material loss and material gain. The sample exposed to artificial saliva did not display significant changes in any parameter.

Gold Leaf-Based Microfluidic Platform for Detection of Essential Oils Using Impedance Spectroscopy.

Drug delivery systems are engineered platforms for the controlled release of various therapeutic agents. This paper presents a conductive gold leaf-based microfluidic platform fabricated using xurography technique for its potential implication in controlled drug delivery operations. To demonstrate this, peppermint and eucalyptus essential oils (EOs) were selected as target fluids, which are best known for their medicinal properties in the field of dentistry. The work takes advantage of the high conductivity of the gold leaf, and thus, the response characteristics of the microfluidic chip are studied using electrochemical impedance spectroscopy (EIS) upon injecting EOs into its micro-channels. The effect of the exposure time of the chip to different concentrations (1% and 5%) of EOs was analyzed, and change in electrical resistance was measured at different time intervals of 0 h (the time of injection), 22 h, and 46 h. It was observed that our fabricated device demonstrated higher values of electrical resistance when exposed to EOs for longer times. Moreover, eucalyptus oil had stronger degradable effects on the chip, which resulted in higher electrical resistance than that of peppermint. 1% and 5% of Eucalyptus oil showed an electrical resistance of 1.79 kΩ and 1.45 kΩ at 10 kHz, while 1% and 5% of peppermint oil showed 1.26 kΩ and 1.07 kΩ of electrical resistance at 10 kHz respectively. The findings obtained in this paper are beneficial for designing suitable microfluidic devices to expand their applications for various biomedical purposes.

Portable Heating and Temperature-Monitoring System with a Textile Heater Embroidered on the Facemask.

Personal heating systems are getting increasing interest because of the need to reduce the negative impact of cold weather on the health of people and animals. Heating the air before inhalation is of great importance as it can reduce the probability of various diseases. In this paper, we present a textile-based heater composed of commercial conductive threads, embroidered on an ordinary protective facemask. We also present the design and implementation details of the temperature monitoring and controlling circuit. Air temperature inside the facemask was monitored by a thermocouple placed in close proximity to the nose (nostrils). Preliminary testing revealed that the difference among temperatures in repeated heating cycles is in the range of ±1.5 °C. The response time for temperature increase from 29.9 to 40.5 °C was about 4 min, while the recovery time from 40.5 to 31.3 °C was about 4.3 min. Safety for human use and wireless data transmission to an application installed on a mobile phone are also demonstrated.

Role of Nanomaterials in the Fabrication of bioNEMS/MEMS for Biomedical Applications and towards Pioneering Food Waste Utilisation.

bioNEMS/MEMS has emerged as an innovative technology for the miniaturisation of biomedical devices with high precision and rapid processing since its first R&D breakthrough in the 1980s. To date, several organic including food waste derived nanomaterials and inorganic nanomaterials (e.g., carbon nanotubes, graphene, silica, gold, and magnetic nanoparticles) have steered the development of high-throughput and sensitive bioNEMS/MEMS-based biosensors, actuator systems, drug delivery systems and implantable/wearable sensors with desirable biomedical properties. Turning food waste into valuable nanomaterials is potential groundbreaking research in this growing field of bioMEMS/NEMS. This review aspires to communicate recent progress in organic and inorganic nanomaterials based bioNEMS/MEMS for biomedical applications, comprehensively discussing nanomaterials criteria and their prospects as ideal tools for biomedical devices. We discuss clinical applications for diagnostic, monitoring, and therapeutic applications as well as the technological potential for cell manipulation (i.e., sorting, separation, and patterning technology). In addition, current in vitro and in vivo assessments of promising nanomaterials-based biomedical devices will be discussed in this review. Finally, this review also looked at the most recent state-of-the-art knowledge on Internet of Things (IoT) applications such as nanosensors, nanoantennas, nanoprocessors, and nanobattery.

A Study of the Performance Degradation of Conductive Threads Based on the Effects of Tensile Forces and Repeated Washing.

In recent years, after the ongoing success in the creation of portable electronic devices, an increasing effort has been put in creating wearable devices capable of sensing multiple parameters while being imperceptible to the user. A field that has recently gained attention due to this is that of textile electronics. For this purpose, one of the most commonly used materials is conductive threads, capable of sustaining an electrical connection, while at the same time being part of a garment. As research on the performance and stability of such threads is scarce, the aim of this work is to study the effects of tension on readily available conductive threads and to verify their suitability and reliability for e-textile applications. After testing seven commercially available threads, this study demonstrates that the nominal parameters provided by the manufacturers are not in line with experimentation, and that both embroidery and washing have an impact on their performance.

Bioactive scaffold (sodium alginate)-g-(nHAp@SiO2@GO) for bone tissue engineering.

Globally, people suffering from bone disorders are steadily increasing and bone tissue engineering is an advanced approach to treating fractured and defected bone tissues. In this study, we have prepared polymeric nanocomposite by free-radical polymerization from sodium alginate, hydroxyapatite, and silica with different GO amounts. The porous scaffolds were fabricated using the freeze drying technique. The structural, morphological, mechanical, and wetting investigation was conducted by Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscope, universal tensile machine, and water contact angle characterization techniques. The swelling, biodegradation, and water retention were also studied. The biological studies were performed (cell viability, cell adherence, proliferation, and mineralization) against osteoblast cell lines. Scaffolds have exhibited different pore morphology SAG-1 (pore size = 414.61 ± 56 µm and porosity = 81.45 ± 2.17 %) and SAG-4 (pore size = 195.97 ± 82 µm and porosity = 53.82 ± 2.45 %). They have different mechanical behavior as SAG-1 has the least compression strength and compression modulus 2.14 ± 2.35 and 16.51 ± 1.27 MPa. However, SAG-4 has maximum compression strength and compression modulus 13.67 ± 2.63 and 96.16 ± 1.97 MPa with wetting behavior 80.70° and 58.70°, respectively. Similarly, SAG-1 exhibited the least and SAG-4 presented maximum apatite mineral formation, cell adherence, cell viability, and cell proliferation against mouse pre-osteoblast cell lines. The increased GO amount provides different multifunctional materials with different characteristics. Hence, the fabricated scaffolds could be potential scaffold materials to treat and regenerate fracture bone tissues in bone tissue engineering.