Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA), and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc), five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group), 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second of 10, but different electric field strengths of 0 (ie, no voltage, control group), 74, 148, 296, and 592 V/cm. Before and after each extraction experiment, skin impedance was measured at 20 Hz.Results: It was found that urea could be extracted transdermally using reverse iontophoresis alone, and further enhancement of extraction could be achieved by combined use of electroporation and reverse iontophoresis. Conversely, PSA and osteopontin were found to be extracted transdermally only by use of reverse iontophoresis and electroporation with a high electrical field strength (>296 V/cm). After application of reverse iontophoresis, electroporation, or a combination of the two techniques, a reduction in skin impedance was observed.Conclusion: Simultaneous transdermal extraction of urea, PSA, and osteopontin is possible only for the condition of applying reverse iontophoresis in conjunction with high electroporation.Keywords: electroporation, reverse iontophoresis, nanochannels, noninvasive, urea, prostate-specific antigen, osteoponti

Body Massage Performance Investigation by Brain Activity Analysis

Massage has been widely applied to improve health and reduce stress. However, the performance difference between hands-on treatment and treatment by mechanical devices has been little mentioned. Therefore, the main aim of this paper is to investigate a subject's EEG performance under massage treatment applied by hand and treatment applied by mechanical devices. Massage was applied to four acupoints for three minutes each. The massage acupoint sequence was from left Jian-wai-yu, right Jian-wai-yu, left Zuo-fei-yu, and finally right Zuo-fei-yu. An EEG system of 32 channels was used. Twenty-four volunteers, mainly college students, were enrolled. EEG rhythm powers of each massage sessions were derived. Two-way ANOVA revealed that there were also significant interactions between the massage stage and the massage type on delta (P < 0.01), theta (P < 0.05), and beta rhythms (P < 0.01), and there were significant differences at different stages for the mechanical massage group (F = 5.557, P < 0.01). The mechanical massage group had more significant differences than the hands-on group for stage coherence of around coherence on alpha rhythm. Further rhythm power scalp topography between two massage methods is also investigated

IoT-based wearable health monitoring device and its validation for potential critical and emergency applications

The COVID-19 pandemic brought the world to a standstill, posing unprecedented challenges for healthcare systems worldwide. The overwhelming number of patients infected with the virus placed an enormous burden on healthcare providers, who struggled to cope with the sheer volume of cases. Furthermore, the lack of effective treatments or vaccines means that quarantining has become a necessary measure to slow the spread of the virus. However, quarantining places a significant burden on healthcare providers, who often lack the resources to monitor patients with mild symptoms or asymptomatic patients. In this study, we propose an Internet of Things (IoT)-based wearable health monitoring system that can remotely monitor the exact locations and physiological parameters of quarantined individuals in real time. The system utilizes a combination of highly miniaturized optoelectronic and electronic technologies, an anti-epidemic watch, a mini-computer, and a monitor terminal to provide real-time updates on physiological parameters. Body temperature, peripheral oxygen saturation (SpO2), and heart rate are recorded as the most important measurements for critical care. If these three physiological parameters are aberrant, then it could represent a life-endangering situation and/or a short period over which irreversible damage may occur. Therefore, these parameters are automatically uploaded to a cloud database for remote monitoring by healthcare providers. The monitor terminal can display real-time health data for multiple patients and provide early warning functions for medical staff. The system significantly reduces the burden on healthcare providers, as it eliminates the need for manual monitoring of patients in quarantine. Moreover, it can help healthcare providers manage the COVID-19 pandemic more effectively by identifying patients who require medical attention in real time. We have validated the system and demonstrated that it is well suited to practical application, making it a promising solution for managing future pandemics. In summary, our IoT-based wearable health monitoring system has the potential to revolutionize healthcare by providing a cost-effective, remote monitoring solution for patients in quarantine. By allowing healthcare providers to monitor patients remotely in real time, the burden on medical resources is reduced, and more efficient use of limited resources is achieved. Furthermore, the system can be easily scaled to manage future pandemics, making it an ideal solution for managing the health challenges of the future

Carbon nanotube composites for glucose biosensor incorporated with reverse iontophoresis function for noninvasive glucose monitoring

This study aims to develop an amperometric glucose biosensor, based on carbon nanotubes material for reverse iontophoresis, fabricated by immobilizing a mixture of glucose oxidase (GOD) and multiwalled carbon nanotubes (MWCNT) epoxy-composite, on a planar screen-printed carbon electrode. MWCNT was employed to ensure proper incorporation into the epoxy mixture and faster electron transfer between the GOD and the transducer. Results showed this biosensor possesses a low detection potential (+500 mV), good sensitivity (4 μA/mM) and an excellent linear response range (r2 = 0.999; 0–4 mM) of glucose detection at +500 mV (versus Ag/AgCl). The response time of the biosensor was about 25 s. In addition, the biosensor could be used in conjunction with reverse iontophoresis technique. In an actual evaluation model, an excellent linear relationship (r2 = 0.986) was found between the glucose concentration of the actual model and the biosensor’s current response. Thus, a glucose biosensor based on carbon nanotube composites and incorporated with reverse iontophoresis function was developed

Non-invasive and transdermal measurement of blood uric acid level in human by electroporation and reverse iontophoresis

The aim of this study was to find out the optimum combination of electroporation (EP) and reverse iontophoresis (RI) on noninvasive and transdermal determination of blood uric acid level in humans. EP is the use of high-voltage electric pulse to create nano-channels on the stratum corneum, temporarily and reversibly. RI is the use of small current to facilitate both charged and uncharged molecule transportation across the skin. It is believed that the combination of these two techniques has additional benefits on the molecules’ extraction across the human skin. In vitro studies using porcine skin and diffusion cell have indicated that the optimum mode for transdermal uric acid extraction is the combination of RI with symmetrical biphasic direct current (current density = 0.3 mA/cm2; phase duration = 180 s) and EP with 10 pulses per second (voltage = 100 V/cm2; pulse width = 1 ms). This optimum mode was applied to six human subjects. Uric acid was successfully extracted through the subjects’ skin into the collection solution. A good correlation (r2 = 0.88) between the subject’s blood uric acid level and uric acid concentrations in collection solutions was observed. The results suggest that it may be possible to noninvasively and transdermally determine blood uric acid levels

A preliminary study of the use of bioimpedance

[[abstract]]Oral cancers are the 11th most common malignancy reported worldwide, accountingfor 3% of all newly diagnosed cancer cases, and one with high mortality ratios among allmalignancies. The objective of this study was to study the electrical properties of canceroustongue tissue (CTT) and normal tongue tissue (NTT). Five tongue cancer patients participatedin this study. A disposable probe incorporating four silver electrodes was used to measure theelectrical properties of CTT and the surrounding NTT of patients. Measurements were performedat six frequencies: 20 Hz; 50 kHz; 1.3 MHz; 2.5 MHz; 3.7 MHz; and 5 MHz, with the amplitudeof the applied voltage limited to 200mV. Four measurement parameters of impedance (Z), phaseangle (θ), real part of impedance (R), and imaginary part of impedance (X) of tongue tissuewere assessed to see if there was any significant difference in the values obtained in CTT andsurrounding NTT. The intraclass correlation coefficient showed that all measurements werereliable. A significant difference (P 0.05 for the four measurement parameters) was foundat 50kHz between CTT and surrounding NTT. It was also found that Z and R of CTT weregenerally smaller than that of surrounding NTT. In conclusion, bioimpedance at a particularfrequency is a potentially promising technique for tongue cancer screening.Keywords: bioimpedance, tongue, cancer, noninvasive, detection, screening

Tissue Electrical Properties Monitoring for the Prevention of Pressure Sore.

[[abstract]]BACKGROUND: Pressure sores are a significant problem in the healthcare sector. Although they may cause considerable morbidity, they are preventable. OBJECTIVES: The objectives of this study are to (1) investigate the electrical properties of a tissue close to and away from the pressure sore site, and (2) establish a new approach for objective, reliable, low-cost and noninvasive screening or detection of pressure sore in its early stage. STUDY DESIGN: Randomised controlled trial. METHODS: Fifteen patients participated in this study. They all had stage I or stage II sacral pressure sores. Tiny surface electrodes in four-electrode configuration were used for all tissue electrical properties measurements recorded over the frequency range of 30-10 MHz. RESULTS: Intraclass correlation coefficient (ICC) showed that all measurements (ICC > 0.90 for all measurements) had good reliability and validity. The real part of impedance (R) and the imaginary part of impedance (X) of a tissue measured close to the pressure sore site was found to be significantly smaller (p < 0.05 in all cases) than that measured away from the pressure sore site at a specific frequency range (R: 30.00-38.55 Hz; X: 43.95-606.40 Hz). It was also found that the extracellular resistance (R(e)) and the ratio of extracellular resistance to intracellular resistance (R(e)/R(i)) of a tissue measured close to the pressure sore site were significantly smaller (p < 0.05 in all cases) than that measured away from the pressure sore site. CONCLUSIONS: Since the electrical properties (R, X, R(e), R(e)/R(i) ) of a tissue close to, and away from, the pressure sore site can be significantly distinguished, a potentially promising method for the screening of pressure sores at an early stage has been proposed