Multi-Modal Spectroscopic Assessment of Skin Hydration.

Human skin acts as a protective barrier, preserving bodily functions and regulating water loss. Disruption to the skin barrier can lead to skin conditions and diseases, emphasizing the need for skin hydration monitoring. The gold-standard sensing method for assessing skin hydration is the Corneometer, monitoring the skin's electrical properties. It relies on measuring capacitance and has the advantage of precisely detecting a wide range of hydration levels within the skin's superficial layer. However, measurement errors due to its front end requiring contact with the skin, combined with the bipolar configuration of the electrodes used and discrepancies due to variations in various interfering analytes, often result in significant inaccuracy and a need to perform measurements under controlled conditions. To overcome these issues, we explore the merits of a different approach to sensing electrical properties, namely, a tetrapolar bioimpedance sensing approach, with the merits of a novel optical sensing modality. Tetrapolar bioimpedance allows for the elimination of bipolar measurement errors, and optical spectroscopy allows for the identification of skin water absorption peaks at wavelengths of 970 nm and 1450 nm. Employing both electrical and optical sensing modalities through a multimodal approach enhances skin hydration measurement sensitivity and validity. This layered approach may be particularly beneficial for minimising errors, providing a more robust and comprehensive tool for skin hydration assessment. An ex vivo desorption experiment was carried out on fresh porcine skin, and an in vivo indicative case study was conducted utilising the developed optical and bioimpedance sensing devices. Expected outcomes were expressed from both techniques, with an increase in the output of the optical sensor voltage and a decrease in bioimpedance as skin hydration decreased. MLR models were employed, and the results presented strong correlations (R-squared = 0.996 and p-value = 6.45 × 10-21), with an enhanced outcome for hydration parameters when both modalities were combined as opposed to independently, highlighting the advantage of the multimodal sensing approach for skin hydration assessment.

Making Sense of Electrical Stimulation: A Meta-analysis for Wound Healing.

Electrical stimulation as a mode of external enhancement factor in wound healing has been explored widely. It has proven to have multidimensional effects in wound healing including antibacterial, galvanotaxis, growth factor secretion, proliferation, transdifferentiation, angiogenesis, etc. Despite such vast exploration, this modality has not yet been established as an accepted method for treatment. This article reviews and analyzes the approaches of using electrical stimulation to modulate wound healing and discusses the incoherence in approaches towards reporting the effect of stimulation on the healing process. The analysis starts by discussing various processes adapted in in vitro, in vivo, and clinical practices. Later it is focused on in vitro approaches directed to various stages of wound healing. Based on the analysis, a protocol is put forward for reporting in vitro works in such a way that the outcomes of the experiment are replicable and scalable in other setups. This work proposes a ground of unification for all the in vitro approaches in a more sensible manner, which can be further explored for translating in vitro approaches to complex tissue stimulation to establish electrical stimulation as a controlled clinical method for modulating wound healing.

Review of Advances in the Measurement of Skin Hydration Based on Sensing of Optical and Electrical Tissue Properties.

The presence of water in the skin is crucial for maintaining the properties and functions of the skin, in particular its outermost layer, known as the stratum corneum, which consists of a lipid barrier. External exposures can affect the skin's hydration levels and in turn, alter its mechanical and physical properties. Monitoring these alterations in the skin's water content can be applicable in clinical, cosmetic, athletic and personal settings. Many techniques measuring this parameter have been investigated, with electrical-based methods currently being widely used in commercial devices. Furthermore, the exploration of optical techniques to measure hydration is growing due to the outcomes observed through the penetration of light at differing levels. This paper comprehensively reviews such measurement techniques, focusing on recent experimental studies and state-of-the-art devices.

Advances in Therapeutic Monitoring of Lithium in the Management of Bipolar Disorder.

Since the mid-20th century, lithium continues to be prescribed as a first-line mood stabilizer for the management of bipolar disorder (BD). However, lithium has a very narrow therapeutic index, and it is crucial to carefully monitor lithium plasma levels as concentrations greater than 1.2 mmol/L are potentially toxic and can be fatal. The quantification of lithium in clinical laboratories is performed by atomic absorption spectrometry, flame emission photometry, or conventional ion-selective electrodes. All these techniques are cumbersome and require frequent blood tests with consequent discomfort which results in patients evading treatment. Furthermore, the current techniques for lithium monitoring require highly qualified personnel and expensive equipment; hence, it is crucial to develop low-cost and easy-to-use devices for decentralized monitoring of lithium. The current paper seeks to review the pertinent literature rigorously and critically with a focus on different lithium-monitoring techniques which could lead towards the development of automatic and point-of-care analytical devices for lithium determination.

Electrotherapies for Glioblastoma.

Non-thermal, intermediate frequency (100-500 kHz) electrotherapies present a unique therapeutic strategy to treat malignant neoplasms. Here, pulsed electric fields (PEFs) which induce reversible or irreversible electroporation (IRE) and tumour-treating fields (TTFs) are reviewed highlighting the foundations, advances, and considerations of each method when applied to glioblastoma (GBM). Several biological aspects of GBM that contribute to treatment complexity (heterogeneity, recurrence, resistance, and blood-brain barrier(BBB)) and electrophysiological traits which are suggested to promote glioma progression are described. Particularly, the biological responses at the cellular and molecular level to specific parameters of the electrical stimuli are discussed offering ways to compare these parameters despite the lack of a universally adopted physical description. Reviewing the literature, a disconnect is found between electrotherapy techniques and how they target the biological complexities of GBM that make treatment difficult in the first place. An attempt is made to bridge the interdisciplinary gap by mapping biological characteristics to different methods of electrotherapy, suggesting important future research topics and directions in both understanding and treating GBM. To the authors' knowledge, this is the first paper that attempts an in-tandem assessment of the biological effects of different aspects of intermediate frequency electrotherapy methods, thus offering possible strategies toward GBM treatment.

Modelling Dynamically Re-Sizeable Electrodes (DRE) for Targeted Transcutaneous Measurements in Impedance Plethysmography.

Impedance plethysmography of extremities typically involves band electrodes around limbs to monitor changes in blood volume. This often causes monitored blood variations to only generate minuscule impedance values relative to the measured baseline, attributed to the tissue surrounding the artery or vein of interest. Smaller, ECG type electrodes can provide a larger signal, however their output is very easily affected by the placement of the electrodes relative to the targeted vasculature. This paper presents a novel method to adjust the active surface of electrodes, introducing Dynamically Re-sizeable Electrodes (DRE), to only target the exact area of interest, forming localised electrodes, without having to manually re-position them. Elongated rectangular electrodes were partitioned into smaller electrode segments, interconnected through custom circuitry. For the development and assessment of the DRE system, work was carried out both experimentally in-vitro on gelatine phantoms using custom switching circuits and through finite element modelling (FEM) simulations in COMSOL. A scanning sequence made use of DRE in single segment variable tetra-pole (SSVT) mode proved capable to identify the transcutaneous location of the blood vessel of interest and the specific electrode segments located in its vicinity. Impedance measurements were then taken using these segments connected to form localised electrodes only placed over the targeted vessel. The resulting localised electrodes exhibited up to [Formula: see text] increased sensitivity to blood variations relative to larger electrodes.

Assessment of the Complex Refractive Indices of Xenopus Laevis Sciatic Nerve for the Optimization of Optical (NIR) Neurostimulation.

Despite an increasing interest in the use of light for neural stimulation, there is little information on how it interacts with neural tissue. The choice of wavelength in most of the optical stimulation literature is based on already available light sources designed for other applications. This paper is the first one to report the complex refractive index of the sciatic nerve of Xenopus laevis, which is a crucial parameter for identifying the optimal wavelength of optical stimuli. The Xenopus laevis neural tissue is the most widely used tissue type in peripheral neurostimulation studies. In this paper, the reflectance ( ) and the transmittance ( ) of the sciatic nerve were measured over a wavelength range of 860-2250 nm, and the corresponding real ( ) and the imaginary ( ) refractive indices were calculated using appropriate formulae in a novel way. The reported values were between 1.3-1.44 and the values are of the order of over the full wavelength range. The absorption coefficient was found to be 100-500 cm . Several localized wavelength ranges were identified that can offer a maximized power coupling between potential optical stimuli and the neural tissue (1150-1200 nm, 1500-1700 nm, and 1900-2050 nm). The narrower regions of 1400-1600 nm and 1850-2150 nm were found to exhibit maximized absorbance. Separately, three regions were identified, where the penetration depths are the greatest (950-1000 nm, 1050-1350 nm, and 1600-1900 nm). This paper provides, for the first time, the fundamental specifications for optimizing the parameters of optical neurostimulation systems.

On the Merits of Tetrapolar Impedance Spectroscopy for Monitoring Lithium Concentration Variations in Human Blood Plasma.

Bipolar disorder is characterized as a manic-depressive psychiatric syndrome with life-threatening risks to the patient. Diagnosed individuals undergo long-term lithium therapy which has proven to be effective for mood stabilization. Maintaining blood lithium concentration levels within a narrow therapeutic window between 0.6 and 1.5 mM is vital for the patient as slightly elevated concentrations of the order of 0.1 mM can be toxic. This paper aims to evaluate the merits of tetrapolar electrical impedance spectroscopy as an alternative method in monitoring blood lithium levels. Measurements were performed using a custom-made tetrapolar probe in human blood plasma with lithium concentrations covering the therapeutic range. The results indicate a limit of detection less than 0.1 mM and a response time of less than 5 s. Prediction of lithium concentration levels using impedance values is in good agreement with conventional standard techniques to approximately 0.05 mM. This technique provides a basis for further development of instrumentation for point of care healthcare technologies.

High-power CMOS current driver with accurate transconductance for electrical impedance tomography.

Current drivers are fundamental circuits in bioimpedance measurements including electrical impedance tomography (EIT). In the case of EIT, the current driver is required to have a large output impedance to guarantee high current accuracy over a wide range of load impedance values. This paper presents an integrated current driver which meets these requirements and is capable of delivering large sinusoidal currents to the load. The current driver employs a differential architecture and negative feedback, the latter allowing the output current to be accurately set by the ratio of the input voltage to a resistor value. The circuit was fabricated in a 0.6- µm high-voltage CMOS process technology and its core occupies a silicon area of 0.64 mm (2) . It operates from a ± 9 V power supply and can deliver output currents up to 5 mA p-p. The accuracy of the maximum output current is within 0.41% up to 500 kHz, reducing to 0.47% at 1 MHz with a total harmonic distortion of 0.69%. The output impedance is 665 k Ω at 100 kHz and 372 k Ω at 500 kHz.

A simulation study of the combined thermoelectric extracellular stimulation of the sciatic nerve of the Xenopus laevis: the localized transient heat block.

The electrical behavior of the Xenopus laevis nerve fibers was studied when combined electrical (cuff electrodes) and optical (infrared laser, low power sub-5 mW) stimulations are applied. Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials (AP). The calculations involve a finite-element model (COMSOL) to represent the electrical properties of the nerve and cuff. Electric-field distribution along the nerve was computed for the given stimulation current profile and imported into a NEURON model, which was built to simulate the electrical behavior of myelinated nerve fiber under extracellular stimulation. The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs. Some preliminary experimental data in support of this conclusion are also shown.

"Capacitive" pulse shapes for platinum cuff electrodes.

Artificial electrical stimulation of the peripheral nervous system is an established therapy for several pathologies and motor impairments. Therapeutic outcomes can be improved with targeted patterns of neural activation, but the required signal amplitudes to achieve this response exceed the limits for safe stimulation. This can lead to electrode corrosion and tissue damage. In this paper, we present a novel approach to pulse shape design based on the properties of the electrode-electrolyte interface. We aim to improve electrode stability at higher voltages by exploiting the potential-independent mechanisms of charge injection. We identified signal parameters associated with capacitive current flow at the platinum interface and incorporated these features into the design of cathodal pulse shapes. A pulse shape comprising 4 high-frequency 'capacitive' harmonics demonstrated a 40 fold performance benefit compared to a conventional square pulse, but irreversible reactions could not be completely avoided during current flow. However, the enhanced electrode stability with the 'capacitive' pulse shapes suggests further optimization of pulse designs according to a surface 'stability function' might allow for safe stimulation with greater electrode voltages.

Tripolar-cuff deviation from ideal model: assessment by bioelectric field simulations and saline-bath experiments.

Ideally, interference in neural measurements due to signals from nearby muscles can be completely eliminated with the use of tripolar cuffs, in combination with appropriate amplifier configurations, such as the quasi-tripole (QT) and the true-tripole (TT). The operation of these amplifiers, is based on the theoretical property of the nerve cuff to produce a linear relationship of potential versus distance along its length, internally, when external potentials appear between its ends. Thus, in principle, electroneurogram (ENG) recordings from an ideal tripolar cuff would be free from electromyogram (EMG) interference generated by nearby muscles. However, in practice the cuff exhibits non-ideal behaviour leading to "cuff imbalance". The main focus of this paper is to investigate the causes of cuff imbalance, to demonstrate that it should be incorporated as a main parameter in the theoretical ENG-recording cuff electrode model. In addition to cuff asymmetry and tissue growth, the proximity of the interference source to the cuff is shown to result in cuff imbalance. The influence of proximity imbalance on the performance of the QT and TT amplifiers is also considered. Proximity imbalance is studied using bioelectric field simulations and saline-bath experiments. Variation is observed with both distance (40 mm and 70 mm was examined) and orientation (0-180 degrees), with the latter causing a more severe effect especially when the source dipole and the cuff are vertical to each other. The simulations and measurements are in close agreement. Tissue growth imbalance and asymmetry imbalance are also investigated in vitro. Finally, the signal-to-interference ratio (SIR; ENG/EMG) of the QT and TT amplifiers is examined in the presence of cuff imbalance. It is shown that proximity imbalance results in their SIR to peak only at certain cuff orientation values. This important finding offers an insight as to why in practice ENG recordings using these amplifiers have been widely reported to be degraded by EMG interference.

The effect of interference source proximity on cuff imbalance.

The presence of cuff imbalance degrades the signal-to-interference (ENG/EMG) ratio in tripolar nerve cuff electrode recordings. Known causes of cuff imbalance include inhomogeneous tissue growth after cuff implantation and cuff manufacturing tolerances. In this paper, we report on an additional contribution to cuff imbalance that stems from variations in orientation and distance of the tripolar cuff relative to the external interference source. The latter is represented here by a dipole. Interference amplitude is also shown to depend on orientation and distance variations, here both factors included in the term "proximity." The study was conducted using field simulations and saline-bath experiments.

On cuff imbalance and tripolar ENG amplifier configurations.

Electroneurogram (ENG) recording techniques benefit from the use of tripolar cuffs because they assist in reducing interference from sources outside the cuff. However, in practice the performance of ENG amplifier configurations, such as the quasi-tripole and the true-tripole, has been widely reported to be degraded due to the departure of the tripolar cuff from ideal behavior. This paper establishes the presence of cuff imbalance and investigates its relationship to cuff asymmetry, cuff end-effects and interference source proximity. The paper also presents a comparison of the aforementioned amplifier configurations with a new alternative, termed the adaptive-tripole, developed to automatically compensate for cuff imbalance. The output signal-to-interference ratio of the three amplifier configurations were compared in vivo for two interference signals (stimulus artifact and M-wave) superimposed on compound action potentials. The experiments showed (for the first time) that the two interference signals result in different cuff imbalance values. Nevertheless, even with two distinct cuff imbalances present, the adaptive-tripole performed better than the other two systems in 61.9% of the trials.