Electrical Skin Impedance Research Articles

Active biointegrated living electronics for managing inflammation.

Seamless interfaces between electronic devices and biological tissues stand to revolutionize disease diagnosis and treatment. However, biological and biomechanical disparities between synthetic materials and living tissues present challenges at bioelectrical signal transduction interfaces. We introduce the active biointegrated living electronics (ABLE) platform, encompassing capabilities across the biogenic, biomechanical, and bioelectrical properties simultaneously. The living biointerface, comprising a bioelectronics layout and a Staphylococcus epidermidis-laden hydrogel composite, enables multimodal signal transduction at the microbial-mammalian nexus. The extracellular components of the living hydrogels, prepared through thermal release of naturally occurring amylose polymer chains, are viscoelastic, capable of sustaining the bacteria with high viability. Through electrophysiological recordings and wireless probing of skin electrical impedance, body temperature, and humidity, ABLE monitors microbial-driven intervention in psoriasis.

Time-Dependent Differences in the Effects of Oleic Acid and Oleyl Alcohol on the Human Skin Barrier.

Oleic acid and oleyl alcohol are commonly used permeation and penetration enhancers to facilitate topical drug delivery. Here, we aimed to better understand the mechanism of their enhancing effects in terms of their interactions with the human skin barrier using diclofenac diethylamine (DIC-DEA), a nonsteroidal anti-inflammatory drug for topical pain management. Oleic acid promoted DIC-DEA permeation through ex vivo human skin more rapidly than oleyl alcohol (both applied at 0.75%) due to fluidization of stratum corneum lipids as revealed by infrared spectroscopy. After 12 h, the effect of these enhancers on DIC-DEA permeation leveled off, fluidization was no longer evident, and skin permeabilization was mainly due to the formation of fluid enhancer-rich domains. Contrary to oleyl alcohol, oleic acid adversely affected two indicators of the skin barrier integrity, transepidermal water loss and skin electrical impedance. The content of oleyl alcohol in the stratum corneum was lower than that of oleic acid (even 12 h after the enhancers were removed from the skin surface), but it caused higher DIC-DEA retention in both epidermis and dermis compared to oleic acid. The effects of oleyl alcohol and oleic acid on DIC-DEA permeation and retention in the skin were similar after a single and repeated application (4 doses every 12 h). Thus, oleyl alcohol offers several advantages over oleic acid for topical drug delivery.

A fabric-based wearable sensor for continuous monitoring of decubitus ulcer of subjects lying on a bed

For multifunctional wearable sensing systems, problems related to wireless and continuous communication and soft, noninvasive, and disposable functionality issues should be solved for precise physiological signal detection. To measure the critical transitions of pressure, temperature, and skin impedance when continuous pressure is applied on skin and tissue, we developed a sensor for decubitus ulcers using conventional analog circuitry for wireless and continuous communication in a disposable, breathable fabric-based multifunctional sensing system capable of conformal contact. By integrating the designed wireless communication module into a multifunctional sensor, we obtained sensing data that were sent sequentially and continuously to a customized mobile phone app. With a small-sized and lightweight module, our sensing system operated over 24 h with a coin-cell battery consuming minimum energy for intermittent sensing and transmission. We conducted a pilot test on healthy subjects to evaluate the adequate wireless operation of the multifunctional sensing system when applied to the body. By solving the aforementioned practical problems, including those related to wireless and continuous communication and soft, noninvasive, and disposable functionality issues, our fabric-based multifunctional decubitus ulcer sensor successfully measured applied pressure, skin temperature, and electrical skin impedance.

Proline, hydroxyproline, and pyrrolidone carboxylic acid derivatives as highly efficient but reversible transdermal permeation enhancers

Overcoming the skin barrier properties efficiently, temporarily, and safely for successful transdermal drug delivery remains a challenge. We synthesized three series of potential skin permeation enhancers derived from natural amino acid derivatives proline, 4-hydroxyproline, and pyrrolidone carboxylic acid, which is a component of natural moisturizing factor. Permeation studies using in vitro human skin identified dodecyl prolinates with N-acetyl, propionyl, and butyryl chains (Pro2, Pro3, and Pro4, respectively) as potent enhancers for model drugs theophylline and diclofenac. The proline derivatives were generally more active than 4-hydroxyprolines and pyrrolidone carboxylic acid derivatives. Pro2–4 had acceptable in vitro toxicities on 3T3 fibroblast and HaCaT cell lines with IC50 values in tens of µM. Infrared spectroscopy using the human stratum corneum revealed that these enhancers preferentially interacted with the skin barrier lipids and decreased the overall chain order without causing lipid extraction, while their effects on the stratum corneum protein structures were negligible. The impacts of Pro3 and Pro4 on an in vitro transepidermal water loss and skin electrical impedance were fully reversible. Thus, proline derivatives Pro3 and Pro4 have an advantageous combination of high enhancing potency, low cellular toxicity, and reversible action, which is important for their potential in vivo use as the skin barrier would quickly recover after the drug/enhancer administration is terminated.

Skin Electrical Impedance Model for Evaluation of the Thickness and Water Content of the Stratum Corneum

Skin Electrical Impedance Model for Evaluation of the Thickness and Water Content of the Stratum Corneum

Low Electrical Resistance Properties of Acupoints: Roles of NOergic Signaling Molecules and Neuropeptides in Skin Electrical Conductance.

Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance. New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness, skin thickness, size of the sensing electrode, pressure applied on the electrode, interelectrode distance, room temperature, and humidity. Morphological studies have identified that blood vessels, hair follicles, and nervous components are enhanced in the meridians/acupoints, which represent areas of potentially high neuronal activity. Recent evidence shows that nitric oxide (NO) concentrations are enhanced in skin acupoints/meridians. L-arginine-derived NO synthesis modifies skin norepinephrine (NE) synthesis/release in acupoints/meridians, and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation. NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1. Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area. Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints. Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field, the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components, and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints. The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system, which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.

Can changes in skin impedance be used to monitor sedation after midazolam and during recovery from anesthesia?

It has been suggested that sympathetic activity, measured as changes in electrical skin impedance (SI), can be used to assess the adequacy of general anesthesia. Our prospective study investigated if measurements of skin impedance can determine levels of sedation induced by midazolam. Twenty-seven patients scheduled for arthroscopy requiring general anesthesia were served as their own control. These were blinded to the order of injections by telling them that they will be randomly administered a placebo (saline) orsedative agent. A DM 3900 multimeter was used for SI measurements. The degree of sedation was measured using the modified Observer's Assessment of Alertness and Sedation (mOAAS) scale. Resting SI values were noted, and all participants were then administered the placebo followed 5 min later by midazolam 2 mg i.v. Five min after that, patients were administered standard general anesthesia with propofol, oxygen, nitrous oxide 60 %, and isoflurane 1 MAC via a laryngeal mask, and sufentanil 5 - 10 µg. SI significantly increased after administration of midazolam and induction of anesthesia. There were no significant differences between pre-administration (baseline) and placebo and end of surgery and end of anesthesia with closed eyes. There were highly significant differences (p<0.001) between pre-administration vs. midazolam, placebo vs. midazolam, pre-administration vs. induction of anesthesia. We found slight correlation between mOAAS and SI. There were no significant changes between the end of surgery and the end of anesthesia with closed eyes, but SI significantly decreased (p<0.01) after eyes opened.

Study of the skin electrical impedance model for assessment of the skin barrier function

Study of the skin electrical impedance model for assessment of the skin barrier function

In vivo electrical impedance measurement in human skin assessment

Abstract Structural and chemical alterations in living tissue are reflected in electrical impedance changes. However, due to the complexity of skin structure, the relation between electrical parameters and physiological/pathological conditions is difficult to establish. The impedance dispersion reflects the clinical status of the examined skin tissue and, therefore, it is frequently used in a non-invasive evaluation of exposing skin to various factors. The method has been used to assess the effect of the fish collagen on the skin of patients suffering from the leg ulcer. Therefore, from a number of different approaches to skin electrical impedance dispersion, the one considered to be safe was selected and applied. This paper presents a short review of different technical approaches to in vivo electrical impedance measurements, as well as an analysis of the results and the effect of fish collagen locally administered on human skin.

Low impedance nature of 12 acupoints on the limbs, and the unexpected dependence on limb angle

OBJECTIVETo better understand the working mechanism of acupuncture, we investigated the skin electrical impedance distribution around acupoints, and the impedance changes at 12 original acupoints bilaterally after bending the limbs. METHODSWe measured the skin electrical impedance in three study subjects in the frequency range of 40 to 10 kHz using the four-electrode method with a sharp probe and a large reference electrode. A measurement matrix of 7 mm × 7 mm with spacing of 2.0 (or 3.0) mm was measured to obtain 2D impedance mapping of acupoints. The impedance spectra of 12 original acupoints were measured at the 0° position and the 90° position. RESULTSThe electrical impedance of some acupoints, such as Yangchi (TE 4), was 16 times lower than that of the surrounding area, showing a recognizable small central area of low impedance with a diameter of less than 4 mm. In contrast, other acupoints, such as Laogong (PC 8), had an electrical impedance that was not significantly different from that of the surrounding area. When the limb was bent from a straight position (0°) to a vertical position (90°), the electrical impedance of the 12 original acupoints showed varied trends, either increasing or decreasing by a factor of up to ten times, or remaining at the same level. CONCLUSIONNot all acupoints tested show the property of low impedance, which might be related to the varied depth of the openings of superficial collaterals. The unexpected dependence of acupoint impedance on limb angle is a novel discovery, which implies that the channel paths are located in interstitial structures in the limbs. It might be possible to determine an optimized limb position for each particular acupuncture treatment in clinical practice.

Young and advanced tumor-some 2D electrodynamic distinctions: melanoma and satellite during a vascular occlusion test: feasibility study.

Conventional methods of electrobioimpedance imaging are not suited for adequate visualization of the skin electrical impedance landscape (SEL) because they do not provide high spatial resolution at large enough area of view. The skin electrodynamics introscopy (SEI) enabled dynamic spectral imaging of the SEL at 32×64mm2 area with 1mm spatial resolution. The focus of the study was to investigate the SEL distinguishing features between early and advanced-stage cancer at the model object of melanoma and its satellite. The analysis of the test-induced SEL metamorphoses was carried out at the periods of blood-stop and blood-restoration. It was found that the young tumor could be reliably visualized and distinguished by its antiphase hypoxia-induced response as compared to that of the advanced one. In response to the blood-restoration, an appearance of newly formed SEL clusters pointed out apparently at vascular abnormalities associated with the tumor. Similar SEL clusterization can be supposedly expected in response to any other test factors which affect cell permeability or/and blood viscosity. The proposed approach might be useful for more thorough mapping and staging malignancies.

Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids.

Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin. To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic. Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin. Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.

Paper-Based Capacitive Touchpad Using Home Inkjet Printer

In this paper, an inkjet-printed paper-based capacitive touchpad is proposed. This touchpad detects finger contact by sensing the change in effective capacitance caused by the skin electrical impedance. A low-cost flexible disposable touchpad with nine capacitive buttons is fabricated, using paper as a substrate. The use of home inkjet printing technology with silver nanoparticle ink makes the fabrication process simple, fast, cheap, and environmentally friendly. The performance of the proposed touchpad is measured with a microcontroller, and tests are conducted for both the cases of finger and touch pen operation. The measured capacitance of the non-touched state is 228–236 pF, whereas the measured capacitance of the touched state is 340–564 pF. The differences in the capacitance of each state are sufficiently large to indicate that a finger has made contact with the touchpad. The sensitivity of the proposed sensor is evaluated, and the parameters of the proposed sensor are compared with those of other paper-based touch pads.

Characterization of skin penetration efficacy by Au-coated Si microneedle array electrode

Investigation of skin penetration efficacy by a silicon microneedle array is presented. Experiments were performed on porcine and chicken skin samples in vitro and on human skin in vivo. Solid microneedle arrays (13×13mm2), each consisting of 100 microneedles, were designed and fabricated by deep reactive ion etching process. To evaluate the penetration efficacy through the mechanically and electrically resistant upper skin layer of stratum corneum, the electrical skin impedance change with applied force was measured by using Au-coated Si microneedle array as working electrode in 2 and 3 electrode configurations. Skin impedance changes between 2 and 8% were measured when applying incremental force, increased from 1 to 10N on a Au metalized microneedle array electrode. When impact assisted penetration of microneedle array was applied instead of incremental increase of applied force, a significant impedance reduction of up to 50% on animal skin and 95% on human skin was obtained, which is a strong evidence of successful skin penetration. Furthermore, the microneedle array electrode showed consistently lower interface impedance compared to the flat electrode for the samples involved. Analyses of Si microneedle mechanical properties revealed that by proper use a satisfactory safety margin (>60) can be achieved.

RegentK and Physiotherapy-Electrodermal Mapping.

BackgroundWithin this study, a new system which measures and analyzes electrical skin impedance in 48 channels within a 2.5 × 3.5 cm matrix is used in rehabilitation medicine for the first time.MethodsElectrodermal activity was measured in 20 patients before and after two different non-surgical treatments of a completely ruptured anterior cruciate ligament. The first treatment, RegentK, was developed by Mohamed Khalifa, the second is a standard physiotherapy.ResultsThe patients in the two groups were age-matched, and all demographic data showed no significant differences. It was interesting that electrodermal activity was significantly decreased only after RegentK.ConclusionWe conclude that not only local effects of pressure application are responsible for these results, rather as yet unknown neurovegetative mechanisms have to be taken into consideration.

Facts and artefacts regarding correlation between skin electrical impedance spectroscopy (EIS) and blood glucose

Earlier observations on possible co-variation between skin EIS and blood glucose prompted us to map and include other factors at play in the predictive model. Skin pH would be one such factor. A cohort of 20 diabetics was investigated, taking around 30 measurements spread over each of two different days 2–21 days apart. Each measurement comprises skin EIT in the frequency range 1kHz to 2.5MHz, skin pH, and immediately evaluated blood samples. There is a co-variation for some, but not all, test persons. The relationship gets stronger on the group level by adding pH-information, but is still poor or non-existent for some test persons. Non-invasive EIS measurements on skin is influenced by skin hydration, blood glucose, skin pH, body location, season, environmental factors, and variables not yet understood. Since impedance related parameters are used to estimate skin hydration, users of such devices should be aware that skin pH may influence as much as the water content of the stratum corneum.

Amino acid derivatives as transdermal permeation enhancers

Transdermal permeation enhancers are compounds that temporarily decrease skin barrier properties to promote drug flux. In this study, we investigated enhancers with amino acids (proline, sarcosine, alanine, β-alanine, and glycine) attached to hydrophobic chain(s) via a biodegradable ester link. The double-chain lipid-like substances displayed no enhancing effect, whereas single-chain substances significantly increased skin permeability. The proline derivative l-Pro2 reached enhancement ratios of up to 40 at 1% concentration, which is higher than that of the well-established and standard enhancers Azone, DDAIP, DDAK, and Transkarbam 12. No stereoselectivity was observed. l-Pro2 acted synergistically with propylene glycol. Infrared studies revealed that l-Pro2 forms a separate liquid ordered phase in the stratum corneum lipids and has no significant effect on proteins. l-Pro2 action was at least partially reversible as measured by skin electrical impedance. Toxicity in keratinocyte (HaCaT) and fibroblast (3T3) cell lines showed IC50 values ranging from tens to hundreds of μM, which is comparable with standard enhancers. Furthermore, l-Pro2 was rapidly decomposed in plasma. In vivo transdermal absorption studies in rats confirmed the enhancing activity of l-Pro2 and suggested its negligible skin toxicity and minimal effect on transepidermal water loss. These properties make l-Pro2 a promising candidate for potential clinical use.

Development and Evaluation of a Novel Four-Electrode Device System for Monitoring Skin Impedance

Qi, meridians, and acupoints are important issues in Chinese medicine. One of the theories claims that acupuncture points and meridians have unique electrical properties. The associations between acupuncture points or meridians and special electrical properties are still under debate. In the current study, we introduced and explained a device for this kind of research and evaluated the reliability of this device as well as effects of pressure, cleaning the skin by alcohol and exfoliation on electrical skin measurements. Fifteen subjects (10 female, 5 male) were recruited to participate in the study. An impedance meter based on the four-electrode technique was designed and fabricated specifically for this study. The effects of pressure, cleaning of the skin by alcohol, and exfoliation on electrical skin impedance were evaluated separately. The device repeatability was also evaluated 30 times in a 30 minutes period. Scale weight up to 200 grams, cleaning the skin with alcohol, and exfoliation didn't affect the performance of this device. The device performance didn't change significantly during the 30 minutes measurement either. The new system we evaluated can be a reliable tool for researches on electrical skin impedance in acupuncture, as its performance is fairly stable even in the presence of various confounding factors such as various pressures on the probe, cleaning the skin with alcohol and exfoliation.

Characterisation of Human Skin Impedance at Acupuncture Point Pc4 Ximen and pericardium meridian using the four-electrode method

Traditional Chinese medicine offers several theories to explain the mechanism of acupuncture. One of these theories proposes that acupuncture points and meridians have unique electrical properties and their electrical skin impedance is lower than surrounding areas. The aim of this study was to evaluate the differences in electrical skin impedance between PC4 and the pericardium meridian compared with the surrounding areas. Eighteen healthy subjects (10 women) were recruited to participate in the study. An impedance meter based on the four-electrode technique was designed specifically for the study. Twenty-five points were marked on the skin: one on the point PC4, four others on the pericardium meridian and 20 points around it. The electrical impedance of each point was measured with the four-electrode device. The mean electrical skin impedance at PC4 was significantly different from the 20 of the surrounding points but not significantly different from the four adjacent points. The mean skin impedance of the five points over the pericardium meridian was significantly different from that of parallel rows of points using repeated measures analysis of variance (p<0.001) Within the possible limits of this measurement technique, skin impedance along the pericardium meridian is lower than surrounding areas, supporting the idea of different properties of the pericardium meridian compared with the control areas. Evidence on skin impedance at PC4 is inconclusive and further studies are needed.

Electrotactile Display with Real-Time Impedance Feedback Using Pulse Width Modulation.

An electrotactile display is a tactile interface composed of skin surface electrodes. The use of such a device is limited by the variability of the elicited sensation. One possible solution to this problem is to monitor skin electrical impedance. Previous studies revealed a correlation between impedance and threshold, but did not construct real-time feedback loops. In this study, an electrotactile display was constructed using a 1.45 μs feedback loop. Real-time pulse width modulation was proposed, and the relationship between skin resistance and absolute threshold was measured to find a function for determining a suitable pulse width from skin resistance. An evaluation experiment revealed that the proposed algorithm suppressed spatial variation and reduced temporal change.