Enhanced Sweat Biosensing with Thread-Embedded Microfluidic Devices.

BACKGROUND This study explored the integration of conductive threads into a microfluidic compact disc (CD), developed using the xurographic method, for a potential sweat biosensing platform. MATERIAL AND METHODS The microfluidic CD platform, fabricated using the xurographic method with PVC films, included venting channels and conductive threads linked to copper electrodes. With distinct microfluidic sets for load and metering, flow control, and measurement, the CD's operation involved spinning for sequential liquid movement. Impedance analysis using HIOKI IM3590 was conducted for saline and artificial sweat solutions on 4 identical CDs, ensuring reliable conductivity and measurements over a 1 kHz to 200 kHz frequency range. RESULTS Significant differences in |Z| values were observed between saline and artificial sweat treatments. 27.5 µL of saline differed significantly from 27.5 µL of artificial sweat, 72.5 µL of saline from 72.5 µL of artificial sweat, and 192.5 µL of saline from 192.5 µL of sweat. Significant disparities in |Z| values were observed between dry fibers and Groups 2, 3, and 4 (varying saline amounts). No significant differences emerged between dry fibers and Groups 6, 7, and 8 (distinct artificial sweat amounts). These findings underscore variations in fiber characteristics between equivalent exposures, emphasizing the nuanced response of the microfluidic CD platform to different liquid compositions. CONCLUSIONS This study shows the potential of integrating conductive threads in a microfluidic CD platform for sweat sensing. Challenges in volume control and thread coating degradation must be addressed for transformative biosensing devices in personalized healthcare.

A Review of the Resistance Mechanisms for ß-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae.

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.

Optimization of Medication Delivery Drone with IoT-Guidance Landing System Based on Direction and Intensity of Light.

This paper presents an optimization of the medication delivery drone with the Internet of Things (IoT)-Guidance Landing System based on direction and intensity of light. The IoT-GLS was incorporated into the system to assist the drone's operator or autonomous system to select the best landing angles for landing. The landing selection was based on the direction and intensity of the light. The medication delivery drone system was developed using an Arduino Uno microcontroller board, ESP32 DevKitC V4 board, multiple sensors, and IoT mobile apps to optimize face detection. This system can detect and compare real-time light intensity from all directions. The results showed that the IoT-GLS has improved the distance of detection by 192% in a dark environment and exhibited an improvement in face detection distance up to 147 cm in a room with low light intensity. Furthermore, a significant correlation was found between face recognition's detection distance, light source direction, light intensity, and light color (p < 0.05). The findings of an optimal efficiency of facial recognition for medication delivery was achieved due to the ability of the IoT-GLS to select the best angle of landing based on the light direction and intensity.

Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.

Does Lower Lean Body Mass Mediate the Relationship Between Falls and Higher Body Mass Index in Asian Older Persons?

The current evidence on the relationship between a higher body mass index (BMI) and falls in older adults is conflicting. This study, therefore, evaluated the relationship between BMI and falls and explored underlying mechanisms for this relationship. Data from 1,340 individuals from the Malaysian Elders Longitudinal Research study, obtained through home-based computer-assisted interviews and followed by hospital-based health checks, were utilized. A history of the presence of falls in the previous 12 months was obtained. The presence of at least one fall in the past 12 months was associated with a higher BMI (odds ratio = 1.03, 95% confidence interval [1.01, 1.06]). The relationship between a higher BMI and falls was, however, attenuated by a lower percentage of lean body mass, which accounted for 69% of the total effect of BMI on the risk of falls. Future studies should now investigate this aforementioned relationship prospectively.

Solutions to Gender Balance in STEM Fields Through Support, Training, Education and Mentoring: Report of the International Women in Medical Physics and Biomedical Engineering Task Group.

The aim of this article is to offer a view of the current status of women in medical physics and biomedical engineering, while focusing on solutions towards gender balance and providing examples of current activities carried out at national and international levels. The International Union of Physical and Engineering Scientists in Medicine is committed to advancing women in science and health and has several initiatives overseen by the Women in Medical Physics and Biomedical Engineering Task Group. Some of the main strategies proposed by the Task Group to attain gender balance are: (a) identify and promote female role models that achieve successful work-life balance, (b) establish programs to develop female leaders, (c) create opportunities for females to increase the international visibility within the scientific community, and (d) establish archives and databases of women in STEM.

Carbon nanotube-based aptasensor for sensitive electrochemical detection of whole-cell Salmonella.

In this study, an amino-modified aptasensor using multi-walled carbon nanotubes (MWCNTs)-deposited ITO electrode was prepared and evaluated for the detection of pathogenic Salmonella bacteria. An amino-modified aptamer (ssDNA) which binds selectively to whole-cell Salmonella was immobilised on the COOH-rich MWCNTs to produce the ssDNA/MWCNT/ITO electrode. The morphology of the MWCNT before and after interaction with the aptamers were observed using scanning electron microscopy (SEM). Cyclic voltammetry and electrochemical impedance spectroscopy techniques were used to investigate the electrochemical properties and conductivity of the aptasensor. The results showed that the impedance measured at the ssDNA/MWCNT/ITO electrode surface increased after exposure to Salmonella cells, which indicated successful binding of Salmonella on the aptamer-functionalised surface. The developed ssDNA/MWCNT/ITO aptasensor was stable and maintained linearity when the scan rate was increased from 10 mV s-1 to 90 mV s-1. The detection limit of the ssDNA/MWCNT/ITO aptasensor, determined from the sensitivity analysis, was found to be 5.5 × 101 cfu mL-1 and 6.7 × 101 cfu mL-1 for S. Enteritidis and S. Typhimurium, respectively. The specificity test demonstrated that Salmonella bound specifically to the ssDNA/MWCNT/ITO aptasensor surface, when compared with non-Salmonella spp. The prepared aptasensor was successfully applied for the detection of Salmonella in food samples.

Investigation of brain electrophysiological properties among heroin addicts: Quantitative EEG and event-related potentials.

This study aims to introduce a new approach of a comprehensive paradigm to evaluate brain electrophysiological properties among addicts. Electroencephalographic spectral power as well as amplitudes and latencies of mismatch negativity (MMN), P300, and P600 components were evaluated among 19 male heroin addicts and 19 healthy nonsmoker subjects using a paradigm consisting of three subparadigms, namely (1) digit span Wechsler test, (2) auditory oddball, and (3) visual cue-reactivity oddball paradigms. Task 1 provided auditory P300 and P600 in association with working memory. Task 2 provided auditory P300 as well as small and large deviant MMN event-related potential (ERPs). Finally, task 3 provided visual cue-reactivity P300. Results show that beta power was higher among heroin addicts while delta, theta, and alpha powers were decreased compared with healthy subjects. ERP analysis confirmed the decline of brain-evoked potential amplitudes when compared with healthy subjects, thus indicating a broad neurobiological vulnerability of preattentive and attentional processing including attentional deficits and compromise of discrimination abilities. The prolonged latency of ERPs reflects poor cognitive capacity in the engagement of attention and memory resources. On the other hand, an increase of attention towards the heroin-related stimuli could be concluded from the increase of P300 in the cue-reactivity condition among heroin addicts. Findings suggest that applying this paradigm in addiction studies benefits comprehensive evaluation of neuroelectrophysiological activity among addicts, which can promote a better understanding of drugs' effects on the brain as well as define new neuroelectrophysiological characteristics of addiction properties. © 2016 Wiley Periodicals, Inc.

Graphene-based label-free electrochemical aptasensor for rapid and sensitive detection of foodborne pathogen.

Reduced graphene oxide (rGO) has emerged as a promising nanomaterial for reliable detection of pathogenic bacteria due to its exceptional properties such as ultrahigh electron transfer ability, large surface to volume ratio, biocompatibility, and its unique interactions with DNA bases of the aptamer. In this study, rGO-azophloxine (AP) nanocomposite aptasensor was developed for a sensitive, rapid, and robust detection of foodborne pathogens. Besides providing an excellent conductive and soluble rGO nanocomposite, the AP dye also acts as an electroactive indicator for redox reactions. The interaction of the label-free single-stranded deoxyribonucleic acid (ssDNA) aptamer with the test organism, Salmonella enterica serovar Typhimurium (S. Typhimurium), was monitored by differential pulse voltammetry analysis, and this aptasensor showed high sensitivity and selectivity for whole-cell bacteria detection. Under optimum conditions, this aptasensor exhibited a linear range of detection from 108 to 101 cfu mL-1 with good linearity (R 2 = 0.98) and a detection limit of 101 cfu mL-1. Furthermore, the developed aptasensor was evaluated with non-Salmonella bacteria and artificially spiked chicken food sample with S. Typhimurium. The results demonstrated that the rGO-AP aptasensor possesses high potential to be adapted for the effective and rapid detection of a specific foodborne pathogen by an electrochemical approach. Graphical abstract Fabrication of graphene-based nanocomposite aptasensor for detection of foodborne pathogen.

Dielectrophoresis for Biomedical Sciences Applications: A Review.

Dielectrophoresis (DEP) is a label-free, accurate, fast, low-cost diagnostic technique that uses the principles of polarization and the motion of bioparticles in applied electric fields. This technique has been proven to be beneficial in various fields, including environmental research, polymer research, biosensors, microfluidics, medicine and diagnostics. Biomedical science research is one of the major research areas that could potentially benefit from DEP technology for diverse applications. Nevertheless, many medical science research investigations have yet to benefit from the possibilities offered by DEP. This paper critically reviews the fundamentals, recent progress, current challenges, future directions and potential applications of research investigations in the medical sciences utilizing DEP technique. This review will also act as a guide and reference for medical researchers and scientists to explore and utilize the DEP technique in their research fields.

Neuroelectrophysiological approaches in heroin addiction research: A review of literatures.

Neuroelectrophysiological properties have been used in human heroin addiction studies. These studies vary in their approach, experimental conditions, paradigms, and outcomes. However, it is essential to integrate previous findings and experimental methods for a better demonstration of current issues and challenges in designing such studies. This Review examines methodologies and experimental conditions of neuroelectrophysiological research among heroin addicts during withdrawal, abstinence, and methadone maintenance treatment and presents the findings. The results show decrements in attentional processing and dysfunctions in brain response inhibition as well as brain activity abnormalities induced by chronic heroin abuse. Chronic heroin addiction causes increased ß and α2 power activity, latency of P300 and P600, and diminished P300 and P600 amplitude. Findings confirm that electroencephalography (EEG) band power and coherence are associated with craving indices and heroin abuse history. First symptoms of withdrawal can be seen in high-frequency EEG bands, and the severity of these symptoms is associated with brain functional connectivity. EEG spectral changes and event-related potential (ERP) properties have been shown to be associated with abstinence length and tend to normalize within 3-6 months of abstinence. From the conflicting criteria and confounding effects in neuroelectrophysiological studies, the authors suggest a comprehensive longitudinal study with a multimethod approach for monitoring EEG and ERP attributes of heroin addicts from early stages of withdrawal until long-term abstinence to control the confounding effects, such as nicotine abuse and other comorbid and premorbid conditions.

Discriminating dengue-infected hepatic cells (WRL-68) using dielectrophoresis.

Dielectrophoresis (DEP), the induced movement of dielectric particles placed in a nonuniform electric field, has been used as a potential technique for manipulation and separation of many biological samples without destructive consequences to the cell. Cells of the same genotype in different physiological and pathological states have unique morphological and structural features, therefore, it is possible to differentiate between them using their DEP responses. This paper reports the experimental discrimination of normal and dengue-infected human hepatic fetal epithelial cells (WRL-68 cells) based on their DEP crossover frequency, at which no resultant movement occurs in the cells in response to the DEP force. A microarray dot electrode was used to conduct the DEP experiments. The DEP forces applied to the cells were quantified by analyzing the light intensity shift within the electrode's dot region based on the Cumulative Modal Intensity Shift image analysis technique. The differences in dielectric properties between infected and uninfected cells were exploited by plotting a unique DEP spectrum for each set of cells. We observed that the crossover frequency decreased from 220 kHz for the normal WRL-68 cells to 140 kHz after infection with the dengue virus in a medium conductivity of 100 µS/cm. We conclude that the change in the DEP crossover frequency between dengue-infected cells and their healthy counterparts should allow direct characterization of these cell types by exploiting their electrophysiological properties.

Bioimpedance Vector Analysis in Diagnosing Severe and Non-Severe Dengue Patients.

Real-time monitoring and precise diagnosis of the severity of Dengue infection is needed for better decisions in disease management. The aim of this study is to use the Bioimpedance Vector Analysis (BIVA) method to differentiate between healthy subjects and severe and non-severe Dengue-infected patients. Bioimpedance was measured using a 50 KHz single-frequency bioimpedance analyzer. Data from 299 healthy subjects (124 males and 175 females) and 205 serologically confirmed Dengue patients (123 males and 82 females) were analyzed in this study. The obtained results show that the BIVA method was able to assess and classify the body fluid and cell mass condition between the healthy subjects and the Dengue-infected patients. The bioimpedance mean vectors (95% confidence ellipse) for healthy subjects, severe and non-severe Dengue-infected patients were illustrated. The vector is significantly shortened from healthy subjects to Dengue patients; for both genders the p-value is less than 0.0001. The mean vector of severe Dengue patients is significantly shortened compare to non-severe patients with a p-value of 0.0037 and 0.0023 for males and females, respectively. This study confirms that the BIVA method is a valid method in differentiating the healthy, severe and non-severe Dengue-infected subjects. All tests performed had a significance level with a p-value less than 0.05.

A Colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) Detection Platform for a Point-of-Care Dengue Detection System on a Lab-on-Compact-Disc.

The enzyme-linked Immunosorbent Assay (ELISA) is the gold standard clinical diagnostic tool for the detection and quantification of protein biomarkers. However, conventional ELISA tests have drawbacks in their requirement of time, expensive equipment and expertise for operation. Hence, for the purpose of rapid, high throughput screening and point-of-care diagnosis, researchers are miniaturizing sandwich ELISA procedures on Lab-on-a-Chip and Lab-on-Compact Disc (LOCD) platforms. This paper presents a novel integrated device to detect and interpret the ELISA test results on a LOCD platform. The system applies absorption spectrophotometry to measure the absorbance (optical density) of the sample using a monochromatic light source and optical sensor. The device performs automated analysis of the results and presents absorbance values and diagnostic test results via a graphical display or via Bluetooth to a smartphone platform which also acts as controller of the device. The efficacy of the device was evaluated by performing dengue antibody IgG ELISA on 64 hospitalized patients suspected of dengue. The results demonstrate high accuracy of the device, with 95% sensitivity and 100% specificity in detection when compared with gold standard commercial ELISA microplate readers. This sensor platform represents a significant step towards establishing ELISA as a rapid, inexpensive and automatic testing method for the purpose of point-of-care-testing (POCT) in resource-limited settings.

The application of biomedical engineering techniques to the diagnosis and management of tropical diseases: a review.

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.

A portable automatic endpoint detection system for amplicons of loop mediated isothermal amplification on microfluidic compact disk platform.

In recent years, many improvements have been made in foodborne pathogen detection methods to reduce the impact of food contamination. Several rapid methods have been developed with biosensor devices to improve the way of performing pathogen detection. This paper presents an automated endpoint detection system for amplicons generated by loop mediated isothermal amplification (LAMP) on a microfluidic compact disk platform. The developed detection system utilizes a monochromatic ultraviolet (UV) emitter for excitation of fluorescent labeled LAMP amplicons and a color sensor to detect the emitted florescence from target. Then it processes the sensor output and displays the detection results on liquid crystal display (LCD). The sensitivity test has been performed with detection limit up to 2.5 × 10(-3) ng/µL with different DNA concentrations of Salmonella bacteria. This system allows a rapid and automatic endpoint detection which could lead to the development of a point-of-care diagnosis device for foodborne pathogens detection in a resource-limited environment.

Development of a passive liquid valve (PLV) utilizing a pressure equilibrium phenomenon on the centrifugal microfluidic platform.

In this paper, we propose an easy-to-implement passive liquid valve (PLV) for the microfluidic compact-disc (CD). This valve can be implemented by introducing venting chambers to control the air flow of the source and destination chambers. The PLV mechanism is based on equalizing the main forces acting on the microfluidic CD (i.e., the centrifugal and capillary forces) to control the burst frequency of the source chamber liquid. For a better understanding of the physics behind the proposed PLV, an analytical model is described. Moreover, three parameters that control the effectiveness of the proposed valve, i.e., the liquid height, liquid density, and venting chamber position with respect to the CD center, are tested experimentally. To demonstrate the ability of the proposed PLV valve, microfluidic liquid switching and liquid metering are performed. In addition, a Bradford assay is performed to measure the protein concentration and evaluated in comparison to the benchtop procedure. The result shows that the proposed valve can be implemented in any microfluidic process that requires simplicity and accuracy. Moreover, the developed valve increases the flexibility of the centrifugal CD platform for passive control of the liquid flow without the need for an external force or trigger.

Recent advances in surface functionalization techniques on polymethacrylate materials for optical biosensor applications.

Biosensor chips for immune-based assay systems have been investigated for their application in early diagnostics. The development of such systems strongly depends on the effective protein immobilization on polymer substrates. In order to achieve this complex heterogeneous interaction the polymer surface must be functionalized with chemical groups that are reactive towards proteins in a way that surface functional groups (such as carboxyl, -COOH; amine, -NH2; and hydroxyl, -OH) chemically or physically anchor the proteins to the polymer platform. Since the proteins are very sensitive towards their environment and can easily lose their activity when brought in close proximity to the solid surface, effective surface functionalization and high level of control over surface chemistry present the most important steps in the fabrication of biosensors. This paper reviews recent developments in surface functionalization and preparation of polymethacrylates for protein immobilization. Due to their versatility and cost effectiveness, this particular group of plastic polymers is widely used both in research and in industry.

Three-dimensional culture environment increases the efficacy of platelet rich plasma releasate in prompting skin fibroblast differentiation and extracellular matrix formation.

Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue regeneration in clinical trials. Although, the mechanism of PRCR effect on fibroblast differentiation has been studied on 2D culture system, a detailed investigation is needed to establish the role of PRCR in cell seeded in 3D scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D and 2D culture systems. Cell viability was measured using MTT assay and DFB differentiation was evaluated by determining the expression levels of nucleostamin and alpha smooth muscle actin (α-SMA), using indirect immunostaining and Western blotting. The expression levels of extracellular matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The PRCR at 10% showed significant effect on cells viability compared with 5% and 20% in both culture environments. The decrease in the expression levels of nucleostamin and the increase in α-SMA signify the DFB differentiation to myofibroblast-like cells that was prominently greater in 3D compared to 2D culture. In 3D culture systems, the total collage production, expression levels of the extracellular matrix gene and the focal adhesion gene were increased significantly compared to 2D culture. In conclusion, 3D culture environments enhances the proliferative and differentiation effects of PRCR on DFB, thereby potentially increases the efficacy of DFB for future tissue engineering clinical application.

Dielectrophoretic manipulation and separation of microparticles using microarray dot electrodes.

This paper introduces a dielectrophoretic system for the manipulation and separation of microparticles. The system is composed of five layers and utilizes microarray dot electrodes. We validated our system by conducting size-dependent manipulation and separation experiments on 1, 5 and 15 µm polystyrene particles. Our findings confirm the capability of the proposed device to rapidly and efficiently manipulate and separate microparticles of various dimensions, utilizing positive and negative dielectrophoresis (DEP) effects. Larger size particles were repelled and concentrated in the center of the dot by negative DEP, while the smaller sizes were attracted and collected by the edge of the dot by positive DEP.