Volume 9 (2018): Issue 1 (January 2018)

Gold electrodes are often not suitable for dopamine measurements as dopamine creates a non-conducting polymer layer on the surface of the electrodes, which leads to increased amount of electrode passivity with the gradual increase in voltammograms measurement. This work presents the impedance spectroscopy and cyclic-voltammetry comparative study for dopamine detection with two modifications for the surface of Au electrodes; cysteamine and mercaptopropionic acid for thermally bonded and ultrasonically welded microfluidic chips, respectively. The effects of optimized tubing selection, bonding techniques, and cleaning methods of the devices with KOH solution played crucial role for improvements in dopamine detection, which are observed in the results. Furthermore, comparison for the modification with unmodified chips, and finding the unknown concentration of dopamine solution using flow injection techniques, is also illustrated.

Although liquid-liquid extraction methods are currently being applied in many areas such as analytical chemistry, biochemical engineering, biochemistry, and biological applications, accessibility and usability of microfluidics in practical daily life fields are still bounded. Suspended microfluidic devices have the potential to lessen the obstacles, but the absence of robust design rules have hampered their usage. The primary objective of this work is to design and fabricate a microfluidic device to quantitatively monitor the drug uptake of cancer cells. Liquid-liquid extraction is used to quantify the drug uptake. In this research work, designs and simulations of two different microfluidic devices for carrying out multiplex solution experiments are proposed to test their efficiency. These simplified miniaturized chips would serve as suspended microfluidic metabolites extraction platform as it allows extracting the metabolites produced from the cancer cells as a result of applying a specific drug type for a certain period of time. These devices would be fabricated by making polydimethylsiloxane (PDMS) molds from the negative master mold using soft lithography. Furthermore, it can leverage to provide versatile functionalities like high throughput screening, cancer cell invasions, protein purification, and small molecules extractions. As per previous studies, PDMS has been depicting better stability with various solvents and has proved to be a reliable and cost effective material to be used for fabrication, though the sensitivity of the chip would be analyzed by cross contamination and of solvents within the channels of device.

An electrical Impedance based tool is designed and developed to aid physicians performing clinical exams focusing on cancer detection. Current research envisions improvement in sensor-based measurement technology to differentiate malignant and benign lesions in human subjects. The tool differentiates malignant anomalies from nonmalignant anomalies using Electrical Impedance Spectroscopy (EIS). This method exploits cancerous tissue behavior by using EIS technique to aid early detection of cancerous tissue.

The correlation between tissue electrical properties and tissue pathologies is identified by offering an analysis technique based on the Cole model. Additional classification and decision-making algorithm is further developed for cancer detection. This research suggests that the sensitivity of tumor detection will increase when supplementary information from EIS and built-in intelligence are provided to the physician.

The objective of this study was to improve the cutoff points of the traditional classification of nutritional status and overweight / obesity based on the BMI in a Brazilian sample. A cross-sectional study was conducted on 1301 individuals of both genders aged 18 to 60 years. The subjects underwent measurement of weight and height and bioelectrical impedance analysis. Simple linear regression was used for statistical analysis, with the level of significance set at p < 0.05. The sample consisted of 29.7% men and 70.3% women aged on averaged 35.7 ± 17.6 years; mean weight was 67.6 ± 16.0 kg, mean height was 164.9 ± 9.5 cm, and mean BMI was 24.9 ± 5.5 kg/m². As expected, lower cutoffs were found for BMI than the classic reference points traditionally adopted by the WHO for the classification of obesity, i.e., 27.15 and 27.02 kg/m² for obesity for men and women, respectively. Other authors also follow this tendency, Romero-Corral et al. (2008) suggested 25.8 to 25.5 kg/m² for American men and women as new values for BMI classification of obesity. Gupta and Kapoor (2012) proposed 22.9 and 28.8 kg/m² for men and women of North India. The present investigation supports other literature studies which converge in reducing the BMI cutoff points for the classification of obesity. Thus, we emphasize the need to conduct similar studies for the purpose of defining these new in populations of different ethnicities.

An approximate semi-analytical solution based on a Hankel transform of a mechanistic model for electrical impedance spectroscopy (EIS) is derived for a non-invasive axisymmetric concentric probe with m electrodes measuring the response of n layers of human skin. We validate the semi-analytical solution for the case when the skin is treated as a three-layer entity - (i) stratum corneum, (ii) viable skin comprising living epidermis and dermis and (iii) adipose tissue – on the volar forearm in the frequency range 1 kHz to 1 MHz with experimental EIS measurements of 120 young subjects. Overall, we find good agreement for both the mean magnitude and phase of the impedance as well as the natural variability between subjects. Finally, the semi-analytical solution is verified with the full set of equations solved numerically: Good agreement is found for the point-wise potential distribution in the three skin layers.

Dominant arm bioimpedance spectroscopy (BIS) and lumbar and hip dual energy X-ray absorptiometry (DXA) measurements were conducted simultaneously on 48 post-menopausal women, aged between 43 and 86 years, with no hip or arm fracture history at Department of Radiology of Istanbul University Cerrahpasa Hospital. According to lumbar DXA results, 21 women were classified as normal, 22 as osteopenia and 5 as osteoporosis; whereas hip DXA results classified 30 women as normal, 15 as osteopenia and 3 as osteoporosis. Only 26 participants had identical lumbar and hip bone mineral density (BMD) diagnostic results. Dominant arm characteristic frequencies of normal subjects were statistically significantly different from osteoporotic subjects based on both lumbar (p < 0.005) and hip classification groups (p < 0.001). Hip and lumbar spine DXA BMD values were significantly correlated (r = 0.55, p < 0.005). The dominant arm BIS characteristic frequency, considered as the single predictor in earlier diagnosis of osteoporosis, was found negatively correlated with DXA measurements for both hip and lumbar spine regions. The Spearman rank correlation coefficient of BIS values with the hip DXA values (r = -0.53, p < 0.001) was higher than that of lumbar spine (r = -0.37, p < 0.001). In receiver operating characteristic (ROC) curve analysis, the best discrimination of dominant arm characteristic frequency was made between normal and osteoporotic subjects based on the hip subgroups (p < 0.001). Both lumbar bone mineral content (BMC) (r = -0.47, p < 0.001) and hip BMC (r = -0.4340, p < 0.005) were statistically significantly correlated with dominant arm characteristic frequency.

Computational dosimetry has become the main tool for estimating induced electric fields within brain tissues in transcranial direct current stimulation (tDCS) which is recently attracting the attention of researches for motor function disturbances such as Parkinson’s disease. This paper investigates the effect of including or excluding the very thin meninges in computing tDCS electric fields using CST software. For this purpose, two models of the brain with and without meninges were used to induce electric field with two DC current electrodes (2 mA) in regions of the model referring to M1 and Prefrontal Cortex (FP2) similar to tDCS. Considering meninges, the results have shown differences in the induced field showing that there might be problems with conventional models in which meninges are not taken into account.

Accurate assessment of experienced pain is a well-known problem in the clinical practices. Therefore, a proper method for pain detection is highly desirable. Electrodermal activity (EDA) is known as a measure of the sympathetic nervous system activity, which changes during various mental stresses. As pain causes mental stress, EDA measures may reflect the felt pain. This study aims to evaluate changes in skin conductance responses (SCRs), skin potential responses (SPRs), and skin susceptance responses (SSRs) simultaneously as a result of sequences of electrical (painful) stimuli with different intensities. EDA responses as results of painful stimuli were recorded from 40 healthy volunteers. The stimuli with three different intensities were produced by using an electrical stimulator. EDA responses significantly changed (increased) with respect to the intensity of the stimuli. Both SCRs and SSRs showed linear relationship with the painful stimuli. It was found that the EDA responses, particularly SCRs (p < 0.001) and SSRs (p = 0.001) were linearly affected by the intensity of the painful stimuli. EDA responses, in particular SCRs, may be used as a useful indicator for assessment of experienced pain in clinical settings.

Bioimpedance measurement systems often use the Howland current sources to excite the biological material under study. Usually, difference or instrumentation amplifiers are used to measure the resulting voltage drop on this material. In these circuits, common mode voltage appears as artifacts in the measurement. Most researches on current sources are focused on improving the output impedance, letting other characteristics aside. In this paper, it is made a brief review on the load common mode voltage and output swing of various topologies of Howland current sources. Three circuits are proposed to reduce load common mode voltage and enhance load capability by using a fully differential amplifier as active component. These circuits are equated, simulated and implemented. The three proposed circuits were able to deliver an output current with cut-off frequency (-3dB) higher than 1 MHz for loads as big as 4.7 kΩ. The worst measured load common mode voltage was smaller than 24 mV for one of the circuits and smaller than 8 mV for the other two. Consequently, it could be obtained increases in the Common Mode Rejection Ratio (CMRR) up to 60 dB when compared to the Enhanced Howland Current Source (EHCS).

The quality of an impedance cardiography (ICG) signal critically impacts the calculation of hemodynamic parameters. These calculations depend solely on the identification of ICG characteristic points on the ABEXYOZ complex. Unfortunately, contrary to the relatively constant morphology of the PQRST complex in electrocardiography, the waveform morphology of ICG data is far from stationary, which causes difficulties in the accuracy of the automated detection of characteristic ICG points. This study evaluated ICG recordings obtained from 10 volunteers. The results indicate that there are several different waveforms for the ABEXYOZ complex; there are up to five clearly distinct waveforms for the ABEXYOZ complex in addition to those that are typically reported. The differences between waveform types increased the difficulty of detecting ICG points. To accurately detect all ICG points, the ABEXYOZ complex should be analyzed according to the corresponding waveform type.

Lung pathologies such as edema, atelectasis or pneumonia are potentially life threatening conditions. Especially in critically ill and mechanically ventilated patients, an early diagnosis and treatment is crucial to prevent an Acute Respiratory Distress Syndrome [1]. Thus, continuous monitoring tool for the lung condition available at the bedside would be highly appreciated. One concept for this is Electrical Impedance Tomography (EIT). In EIT, an electrode belt of typically 16 or 32 electrodes is attached at the body surface and multiple impedance measurements are performed. From this, the conductivity change inside the body is reconstructed in a two-dimensional image. In various studies, EIT proved to be a useful tool for quantifying recruitment maneuvers, the assessment of the ventilation homogeneity, the detection of lung edema or perfusion monitoring [2, 3, 4, 5]. Nevertheless, the main problem of EIT is the low spatial resolution (compared to CT) and the limitation to two dimensional images. In this paper, we try to address the latter issue: Instead of projecting conductivity changes onto a two-dimensional image, we adjust electrode positions to focus single tetrapolar measurements to specific, three-dimensional regions of interest. In earlier work, we defined guidelines to achieve this focusing [6, 7]. In this paper, we demonstrate in simulations and in a water tank experiment that applying these guidelines can help to detect pathologies in specific lung regions.

Overweight, obese and chronic kidney disease patients have an altered and negative body composition being its assessment important. Bioelectrical impedance analysis is an easy-to-operate and low-cost method for this purpose. This study aimed to compare and correlate data from single- and multi-frequency bioelectrical impedance spectroscopy applied in subjects with different body sizes, adiposity, and hydration status. It was a cross-sectional study with 386 non-chronic kidney disease volunteers (body mass index from 17 to 40 kg/m²), 30 patients in peritoneal dialysis, and 95 in hemodialysis. Bioelectrical impedance, body composition, and body water data were assessed with single- and multi-frequency bioelectrical impedance spectroscopy. Differences (95% confidence interval) and agreements (Bland-Atman analyze) between devices were evaluated. The intraclass correlation coefficient was used to measure the strength of agreement and Pearson’s correlation to measure the association. Regression analyze was performed to test the association between device difference with body mass index and overhydration. The limits of agreement between devices were very large. Fat mass showed the greatest difference and the lowest intraclass and Pearson’s correlation coefficients. Pearson’s correlation varied from moderate to strong and the intraclass correlation coefficient from weak to substantial. The difference between devices were greater as body mass index increased and was worse in the extremes of water imbalance. In conclusion, data obtained with single- and multi-frequency bioelectrical impedance spectroscopy were highly correlated with poor agreement; the devices cannot be used interchangeably and the agreement between the devices was worse as body mass index and fat mass increased and in the extremes of overhydration.

In a succession of articles published over 65 years ago, Sir Alan Lloyd Hodgkin and Sir Andrew Fielding Huxley established what now forms our physical understanding of excitation in nerve, and how the axon conducts the action potential. They uniquely quantified the movement of ions in the nerve cell during the action potential, and demonstrated that the action potential is the result of a depolarizing event across the cell membrane. They confirmed that a complete depolarization event is followed by an abrupt increase in voltage that propagates longitudinally along the axon, accompanied by considerable increases in membrane conductance. In an elegant theoretical framework, they rigorously described fundamental properties of the Na⁺ and K⁺ conductances intrinsic to the action potential.

Notwithstanding the elegance of Hodgkin and Huxley’s incisive and explicative series of discoveries, their model is mathematically complex, relies on no small number of stochastic factors, and has no analytical solution. Solving for the membrane action potential and the ionic currents requires integrations approximated using numerical methods. In this article I present an analytical formalism of the nerve action potential, V_m and that of the accompanying cell membrane electric field, E_m. To conclude, I present a novel description of V_m in terms of a single, nonlinear differential equation. This is an original stand-alone article: the major contribution is the latter, and how this description coincides with the cell membrane electric field. This work has necessitated unifying information from two preceding papers [1,2], each being concerned with the development of closed-form descriptions of the nerve action potential, V_m.

The objective of this work is to develop a technique for filtering parasitic effects from the impedance spectra (IS) measured in biological material phantoms. IS data are contaminated with unexpected capacitive and inductive effects from cable, input/output amplifiers capacitances, electrode polarization, temperature and contact pressure when collecting data. It is proposed a model which contains an RLC-network in series with the Cole model (RSC), then called RLC-Cole. It was built four circuits composed by resistors, capacitors and inductors. An impedance analyzer (HF2IS) was used to perform the measurements in the frequency range of 1 to 3000 kHz. Data were fitted into the model and comparisons to the nominal values were made. In order to validate the proposed model, a gelatin phantom and a chicken breast muscle impedance spectra were also collected and analyzed. After filtering, Cole fitting was performed. Results showed a maximum root-mean-square error of 1% for the circuits, 2.63% for the gelatin phantom, whereas 2.01% for the chicken breast. The RLC-Cole model could significantly remove parasitic effects out of a tissue impedance spectrum measured by a 4-point electrode probe. This may be highly important in EIS systems whose objective is to discriminate a normal tissue from a cancerous one.

Neuromonitoring is performed to prevent further (secondary) brain damage by detecting low brain blood flow following a head injury, stroke or neurosurgery. This comparative neuromonitoring study is part of an ongoing investigation of brain bioimpedance (rheoencephalography-REG) as a measuring modality for use in both civilian and military medical settings, such as patient transport, emergency care and neurosurgery intensive care. In a previous animal study, we validated that REG detects cerebral blood flow autoregulation (CBF AR), the body’s physiological mechanism that protects the brain from adverse effects of low brain blood flow (hypoxia/ischemia). In the current descriptive pig study, the primary goal was to compare measurements of CBF AR made with REG to measurements made with other neuromonitoring modalities: laser Doppler flow (LDF); intracranial pressure (ICP); absolute CBF; carotid flow (CF); and systemic arterial pressure (SAP). Challenges administered to anesthetized pigs were severe induced hemorrhage (bleeding) and resuscitation; CO₂ inhalation; and positive end expiratory pressure (PEEP). Data were stored on a computer and processed offline. After hemorrhage, the loss of CBF AR was detected by REG, ICP, and CF, all of which passively followed systemic arterial SAP after bleeding. Loss of CBF AR was the earliest indicator of low brain blood flow: loss of CBF AR occurred before a decrease in cardiac output, which is the cardiovascular response to hemorrhage. A secondary goal of this study was to validate the usefulness of new automated data processing software developed to detect the status of CBF AR. Both the new automated software and the traditional (observational) evaluation indicated the status of CBF AR. REG indicates the earliest breakdown of CBF AR; cessation of EEG for 2 seconds and respiration would be used as additional indicators of loss of CBF AR. The clinical significance of this animal study is that REG shows potential for use as a noninvasive, continuous and non-operator dependent neuromonitor of CBF AR in both civilian and military medical settings. Human validation studies of neuromonitoring with REG are currently in progress.

Different excitation signals are applicable in the wideband impedance spectroscopy in general. However, in electrical bioimpedance (EBI) measurements, there are limitations that set specific demands on the properties of the excitation signals. This paper compares the efficiency of different excitation signals in a graspable presentation and gives recommendations for their use. More exactly, the paper deals with finding the efficient excitation waveforms for the fast spectroscopy of electrical bioimpedance. Nevertheless, the described solutions could be useful also in other implementations of impedance spectroscopy intended for frequency domain characterization of different objects.

Rapid development in the field of tissue engineering necessitates implementation of monitoring methods for evaluation of the viability and characteristics of the cell cultures in a real-time, non-invasive and non-destructive manner. Current monitoring techniques are mainly histological and require labeling and involve destructive tests to characterize cell cultures. Bioimpedance measurement technique which benefits from measurement of electrical properties of the biological tissues, offers a non-invasive, label-free and real-time solution for monitoring tissue engineered constructs. This review outlines the fundamentals of bioimpedance, as well as electrical properties of the biological tissues, different types of cell culture constructs and possible electrode configuration set ups for performing bioimpedance measurements on these cell cultures. In addition, various bioimpedance measurement techniques and their applications in the field of tissue engineering are discussed.

The term sensitivity is sometimes misused when discussing volume impedance measurements. This is a critique of the name of the quantity sensitivity, as well as pointing out how the term easily can be misinterpreted. To resolve the issue, a shift of focus towards volume impedance density, which is a more useful quantity, is proposed. A new parameter, perceptivity, is introduced. Perceptivity is useful tool for characterization of measurement systems, to objectively compare systems, and to formulate instrument specifications.

In biomedical MITS, slight unintentional movements of the patient during measurement can contaminate the aimed images to a great extent. This study deals with measurement optimization in biomedical MITS through the detection of these unpredictable movements during measurement and the elimination of the resulting movement artefacts in the images to be reconstructed after measurement. The proposed detection and elimination (D&E) methodology requires marking the surface of the object under investigation with specific electromagnetically perturbing markers during multi-frame measurements. In addition to the active marker concept already published, a new much simpler passive marker concept is presented. Besides the biological signal caused by the object, the markers will perturb the primary magnetic field inducing their own signals. The markers' signals will be used for the detection of any unwanted object movements and the signal frames corrupted thereby. The corrupted signal frames will be then excluded from image reconstruction in order to prevent any movement artefacts from being imaged with the object. In order to assess the feasibility of the developed D&E technique, different experiments followed by image reconstruction and quantitative analysis were performed. Hereof, target movements were provoked during multifrequency, multiframe measurements in the β-dispersion frequency range on a saline phantom of physiological conductivity. The phantom was marked during measurement with either a small single-turn coil, an active marker, or a small soft-ferrite plate, a passive marker. After measurement, the erroneous phantom signals were corrected according to the suggested D&E strategy, and images of the phantom before and after correction were reconstructed. The corrected signals and images were then compared to the erroneous ones on the one hand, and to other true ones gained from reference measurements wherein no target movements were provoked on the other hand. The obtained qualitative and quantitative measurement and image reconstruction results showed that the erroneous phantom signals could be accurately corrected, and the movement artefacts could be totally eliminated, verifying the applicability of the novel D&E technique in measurement optimization in biomedical MITS and supporting the proposed aspects.

Tetra-polar electrical impedance measurement (TPIM) with a square geometry of electrodes is useful in the characterization of epithelial tissues, especially in the detection of cervical cancer at precancerous stages. However, in TPIM, the peak planar sensitivity just below the electrode surface is almost zero and increases to a peak value at a depth of about one third to one half of the electrode separation. To get high sensitivity for the epithelial layer, having thicknesses of 200 μm to 300 μm, the electrode separation needed is less than 1 mm, which is difficult to achieve in practical probes. This work proposes a conical conducting layer in front of a pencil like probe with a square geometry of TPIM electrodes to create virtual electrodes with much smaller separation at the body surface, thus increasing the sensitivity of the epithelial tissues. To understand the improvements, if any, 3D sensitivity distribution and transfer impedance were simulated using COMSOL Multiphysics software for a simplified body tissue model containing a 300 μm epithelial layer. It has been shown that fractional contribution of an epithelial layer can be increased several times placing a cylindrical conducting layer in between the tissue surface and the electrodes, which can further be enhanced using a conical conducting layer. The results presented in this paper can be used to choose an appropriate electrode separation, conducting layer height and cone parameters for enhanced sensitivity in the epithelial layer.

It has been demonstrated before that human skin can be modeled as a memristor (memory resistor). Here we realize a memristor bridge by applying two voltages of opposite signs at two different skin sites. By this setup it is possible to use human skin as a frequency doubler and half-wave rectifier which is an application of the non-linear electrical properties of human skin. The corresponding electrical measurements are non-linear since these are affected by the applied stimulus itself.