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In this study, a novel aptasensor based on a transition metal oxide-modified pencil graphite electrode (PGE) was developed for the diagnosis of early-stage prostate cancer (PCa) via monitoring the prostate-specific antigen (PSA), which is the main biomarker for PCa. Single-use PGEs modified with pulsed deposited manganese oxide (MnOx) film were used to attach the amino-terminated aptamer specific to the PSA via carbodiimide chemistry. The designed aptasensor was placed in an electrochemical cell containing ferri/ferrocyanide ions as a redox probe to measure the charge transfer resistances (R ct ) of the electrode surface by electrochemical impedance spectroscopy (EIS) to follow the response of each modification step. The effect of the medium pH on the ionic structure of the aptamer molecule according to its pI value and, thus, the reversing of the direction of the response (ΔR ct ) by the pH change was also discussed. The level of PSA secreted from PCa cells was investigated using impedimetric transduction. The specificity of the aptasensor was validated through selectivity studies against non-specific tumor markers like VEGF and different cancer cell lines including breast cancer and androgen-insensitive prostate cancer. The developed system showcases a label-free, fast, specific, and cost-effective approach for PSA detection, highlighting the importance of medium pH and the electrostatic environment on the aptamer's response. Our work emphasizes the potential for such aptasensors in clinical diagnostics and paves the way for further exploration into using transition metal oxides in biosensing applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To assess whether bioimpedance spectroscopy analysis (BIA) can be used as a tool to guide postoperative fluid management in patients undergoing cardiac surgery., Design: An observational study., Setting: A single tertiary hospital., Participants: Patients who underwent cardiac surgery with cardiopulmonary bypass between June and November 2023 who were able to undergo BIA measurements., Interventions: None., Measurements and Main Results: Correlations between BIA measurements of extracellular fluid (ECF) and total body water (TBW) volumes and daily changes in weight and 24-hour net intake and output (I/O) of fluids were assessed. Correlations between predischarge ECF volume as a percentage of TBW volume (ECF%TBW) and predischarge pro-B-type natriuretic peptide (Pro-BNP) levels and readmissions were analyzed. Changes in daily ECF volume significantly correlated with daily weight changes (p < 0.01) and 24-hour I/O (p < 0 .01). TBW volume significantly correlated with daily weight changes (p < 0.01) and with 24-hour I/O (p = 0.04). Daily weight changes did not correlate with 24-hour I/O (p = 0.06). The patients with predischarge ECF%TBW(%) greater than or equal to 51 had significantly higher predischarge Pro-BNP than those with ECF%TBW(%) less than 51 (p < 0.01). Patients who had heart failure revisits or admissions after discharge had a higher predischarge ECF%TBW(%) on index admission compared with patients who did not have heart failure readmissions (p = 0.01)., Conclusions: BIA measurements in postoperative cardiac surgery patients may be a valuable tool to quantitatively determine fluid status to help guide fluid management in this patient population. Further studies validating the use of BIA for postoperative care in this population are warranted., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Three-dimensional human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in preclinical investigative dermatology and regulatory toxicology. In this study, we investigated the utility of electrical impedance spectroscopy (EIS) for noninvasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for 7 consecutive days did not impact epidermal morphology, and readouts showed comparable trends with HEEs measured only once. We determined 2 frequency ranges in the resulting impedance spectra: a lower frequency range termed EIS diff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EIS SC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9-engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR, or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EIS diff . Exposure to proinflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EIS diff . This cytokine-associated decrease in EIS diff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a noninvasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects, and repair., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Plant stress diagnosis is essential for efficient crop management and productivity increase. Under stress, plants undergo physiological and compositional changes. Vegetation indices obtained from leaf reflectance spectra and bioimpedance spectroscopy provide information about the external and internal aspects of plant responses, respectively. In this study, bioimpedance and vegetation indices were noninvasively acquired from sweet basil (Ocimum basilicum L.) leaves exposed to three types of stress (drought, salinity, and chilling). Integrating the vegetation index, a novel approach, contains information about the surface of plants and bioimpedance data, which indicates the internal changes of plants. The fusion of these two datasets was examined to classify the types and severity of stress. Among the eight supervised machine learning models (three linear and five non-linear), the support vector machine (SVM) exhibited the highest accuracy in classifying stress types. Bioimpedance spectroscopy alone exhibited an accuracy of 0.86 and improved to 0.90 when fused with vegetation indices. Additionally, for drought and salinity stresses, it was possible to classify the early stage of stress with accuracies of 0.95 and 0.93, respectively. This study will allow us to classify the different types and severity of plant stress, prescribe appropriate treatment methods for efficient cost and time management of crop production, and potentially apply them to low-cost field measurement systems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Soo Chung reports financial support was provided by Electronics and Telecommunications Research Institute. Daesik Son reports financial support was provided by Electronics and Telecommunications Research Institute. Junyoung Park reports financial support was provided by Electronics and Telecommunications Research Institute. Siun Lee reports financial support was provided by Electronics and Telecommunications Research Institute. Jae Joon Kim reports financial support was provided by Institute of Information & communications Technology Planning & Evaluation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Conventional approaches for bacterial cell analysis are hindered by lengthy processing times and tedious protocols that rely on gene amplification and cell culture. Impedance spectroscopy has emerged as a promising tool for efficient real-time bacterial monitoring, owing to its simple, label-free nature and cost-effectiveness. However, its limited practical applications in real-world scenarios pose a significant challenge. In this review, we provide a comprehensive study of impedance spectroscopy and its practical utilization in bacterial system measurements. We begin by outlining the fundamentals of impedance theory and modeling, specific to bacterial systems. We then offer insights into various strategies for bacterial cell detection and discuss the role of impedance spectroscopy in antimicrobial susceptibility testing (AST) and single-cell analysis. Additionally, we explore key aspects of impedance system design, including the influence of electrodes, media, and cell enrichment techniques on the sensitivity, specificity, detection speed, concentration accuracy, and cost-effectiveness of current impedance biosensors. By combining different biosensor design parameters, impedance theory, and detection principles, we propose that impedance applications can be expanded to point-of-care diagnostics, enhancing their practical utility. This Perspective focuses exclusively on ideally polarizable (fully capacitive) electrodes, excluding any consideration of charge transfer resulting from Faradaic reactions.

Electrochemical impedance spectroscopy (EIS) is a non-invasive and label-free method widely used for characterizing cell cultures and monitoring their structure, behavior, proliferation and viability. Microfluidic systems are often used in combination with EIS methods utilizing small dimensions, controllable physicochemical microenvironments and offering rapid real-time measurements. In this work, an electrode array capable of conducting EIS measurements was integrated into a multichannel microfluidic chip which is able to trap individual cells or cell populations in specially designed channels comparable to the size of cells. An application-specific printed circuit board (PCB) was designed for the implementation of the impedance measurement in order to facilitate connection with the device used for taking EIS spectra and for selecting the channels to be measured. The PCB was designed in consideration of the optical screening of trapped cells in parallel with the EIS measurements which allows the comparison of EIS data with optical signals. With continuous EIS measurement, the filling of channels with cell suspension can be followed. Yeast cells were trapped in the microfluidic system and EIS spectra were recorded considering each individual channel, which allows differentiating between the number of trapped cells.

Background: The PREVENT randomized control trial monitored progression to chronic breast cancer-related lymphedema (cBCRL) following intervention for subclinical breast cancer-related lymphedema (sBCRL) assessed by bioimpedance spectroscopy (BIS) versus tape-measure (TM). This multi-institutional trial demonstrated a 92% risk reduction of developing cBCRL. This secondary analysis reviews the timing of sBCRL and cBCRL following breast cancer (BC) treatment., Patients and Methods: Women at risk of cBCRL (n = 919) were screened regularly up to 36 months after BC treatment using either BIS or TM. Following diagnosis of sBCRL, patients underwent a 4-week compression sleeve intervention. The time in months from BC treatment to detection was reviewed at 3-month intervals., Results: In total 209 patients developed sBCRL (BIS: n = 89, TM: n = 120) and were eligible for intervention. 30 progressed to cBCRL postintervention (BIS: 7, TM: 23). More than half of patients had measurements consistent with sBCRL within 9 months of BC treatment. Patients continued to have initial detections of sBCRL, regardless of screening method, with rates remaining consistent in years two and three (p > 0.242) post surgery. Additionally, 39 patients progressed to cBCRL without developing sBCRL or receiving intervention across the 3-year period., Conclusions: The timing of sBCRL detection demonstrates that patients continue to be at risk years after treatment and may continue to progress to cBCRL years after surgery. Early detection of sBCRL allows for early intervention decreasing the likelihood of progression to cBCRL. Patients should continue to be monitored for a minimum of 3 years following completion of cancer treatment. Specifically, careful targeted monitoring over the initial 9-month period is important., (© 2024. Society of Surgical Oncology.)

This paper presents a low-noise bioimpedance (bio-Z) spectroscopy interface for electrical impedance myography (EIM) over the 1 kHz to 2 MHz frequency range. The proposed interface employs a sinusoidal signal generator based on direct-digital-synthesis (DDS) to improve the accuracy of the bio-Z reading, and a quadrature low-intermediate frequency (IF) readout to achieve a good noise-to-power efficiency and the required data throughput to detect muscle contractions. The readout is able to measure baseline and time-varying bio-Z by employing robust and power-efficient low-gain IAs and sixth-order single-bit bandpass (BP) ∆Σ ADCs. The proposed bio-Z spectroscopy interface is implemented in a 180 nm CMOS process, consumes 344.3 - 479.3 μW, and occupies 5.4 mm 2 area. Measurement results show 0.7 m Ω/[Formula: see text] sensitivity at 15.625 kHz, 105.8 dB SNR within 4 Hz bandwidth, and a 146.5 dB figure-of-merit. Additionally, recording of EIM in time and frequency domain during contractions of the bicep brachii muscle demonstrates the potential of the proposed bio-Z interface for wearable EIM systems.

Background: Accurate volume status assessment and dry weight achievement are the most challenging goals for a nephrologist. We aimed to evaluate the role of ultrasonographic parameters including lung ultrasound and inferior vena cava (IVC) measurements as practical methods of volume status assessment in children on hemodialysis by comparing them with established techniques, such as clinical evaluation and bioimpedance spectroscopy., Methods: A prospective cross-sectional study compared pre- and post-dialysis volume status using bioimpedance spectroscopy (BIS) parameters and clinical data with ultrasonographic lung B-lines and IVC parameters in children on regular hemodialysis., Results: A total 60 children (mean age 9.4 ± 2.8 years) were enrolled. Twenty patients (33.3%) were clinically overloaded to varying degrees (17 patients had mild to moderate signs of fluid overload and 3 patients had moderate to severe signs of fluid overload). All other patients (66.7%) were clinically euvolemic. Sonographic parameters were significantly lower post-dialysis than pre-dialysis, including lung B-line count and IVC diameter. IVC collapsibility index mean was significantly higher post-dialysis than pre-dialysis. There was a significant correlation between the lung B-line count, IVC parameters, and BIS-measured overhydration both before and after hemodialysis. Nine patients had ≥ 8 B-lines post-dialysis, only three of them were hypertensive., Conclusions: Clinical criteria alone are not specific for determining accurate fluid status in pediatric hemodialysis patients. Lung B-line score, IVC parameters, and BIS may be complementary to each other and to clinical data. Lung B-lines outperform IVC measurements and BIS in subclinical volume overload detection in pediatric hemodialysis patients., (© 2024. The Author(s).)

Background: Bioimpedance devices are practical for measuring body composition in preschool children, but their application is limited by the lack of validated equations., Objectives: To develop and validate fat-free mass (FFM) bioimpedance prediction equations among New Zealand 3.5-year olds, with dual-energy X-ray absorptiometry (DXA) as the reference method., Methods: Bioelectrical impedance spectroscopy (SFB7, ImpediMed) and DXA (iDXA, GE Lunar) measurements were conducted on 65 children. An equation incorporating weight, sex, ethnicity, and impedance was developed and validated. Performance was compared with published equations and mixture theory prediction., Results: The equation developed in ~70% (n = 45) of the population (FFM [kg] = 1.39 + 0.30 weight [kg] + 0.39 length 2 /resistance at 50 kHz [cm 2 /Ω] + 0.30 sex [M = 1/F = 0] + 0.28 ethnicity [1 = Asian/0 = non-Asian]) explained 88% of the variance in FFM and predicted FFM with a root mean squared error of 0.39 kg (3.4% of mean FFM). When internally validated (n = 20), bias was small (40 g, 0.3% of mean FFM), with limits of agreement (LOA) ±7.6% of mean FFM (95% LOA: -0.82, 0.90 kg). Published equations evaluated had similar LOA, but with marked bias (>12.5% of mean FFM) when validated in our cohort, likely due to DXA differences. Of mixture theory methods assessed, the SFB7 inbuilt equation with personalized body geometry values performed best. However, bias and LOA were larger than with the empirical equations (-0.43 kg [95% LOA: -1.65, 0.79], p < 0.001)., Conclusions: We developed and validated a bioimpedance equation that can accurately predict FFM. Further external validation of the equation is required., (© 2023. The Author(s).)

Coronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture-prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high-risk atherosclerotic features that portend rupture risk. In this single-center, prospective study, n = 26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N = 61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture-risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas-under-the-curve (AUC). Necrotic cores were identified in n = 19 vessels (median area 1.53 mm 2 ) with a median fibrous cap thickness of 62 μm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm 2 versus <1.75 mm 2 (19.8 ± 4.4 kΩ vs. 7.2 ± 1.0 kΩ, p = .019), fibrous cap thickness ≤65 μm versus >65 μm (19.1 ± 3.5 kΩ vs. 6.5 ± 0.9 kΩ, p = .004), and ≥20 macrophages per 0.3 mm-diameter high-power field (HPF) versus <20 macrophages per HPF (19.8 ± 4.1 kΩ vs. 10.2 ± 0.9 kΩ, p = .002). Impedance identified necrotic core area ≥1.75 mm 2 , fibrous cap thickness ≤65 μm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716-1.000) (p = .013), 0.852 (0.646-1.000) (p = .025), and 0.835 (0.577-1.000) (p = .028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573-0.962) (p = .035). EIS discriminates high-risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography-guided atherosclerosis evaluation., (© 2024 Federation of American Societies for Experimental Biology.)

A new, sensitive, and cost-effective lab-on-paper-based immunosensor was designed based on electrochemical impedance spectroscopy (EIS) for the detection of exosomes. EIS was selected as the determination method since there was a surface blockage in electron transfer by binding the exosomes to the transducer. Briefly, the carbon working electrode (WE) on the paper electrode (PE) was modified with gold particles (AuPs@PE) and then conjugated with anti-CD9 (Anti-CD9/AuPs@PE) for the detection of exosomes. Variables involved in the biosensor design were optimized with the univariate mode. The developed method presents the limit of detection of  8.7 × 10 2 exosomes mL -1 , which is lower than that of many other available methods under the best conditions. The biosensor was also tested with urine samples from cancer patients with high recoveries. Due to this  a unique, low-cost, biodegradable technology is presented that can directly measure exosomes without labeling them for early cancer or metastasis detection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The recent investigation targets to use adapted carbon paste (CP) with copper nanoparticles (CuNs) operating in a phosphate buffer (PBS) medium with a pH range of 5.0-8.0, to synthesize a novel, susceptible, and simple electrochemical sensor for the detection of one of the most important drugs, vitamin B 6 . Copper (Cu) is one of the most three common essential trace elements found in the bodies of both humans and animals, along with iron and zinc for all crucial physiological and biochemical functions. Its properties, which are assessed using a variety of methods including scanning electron microscopy (SEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), have also drawn a lot of attention recently. We considered the effects of pH, buffer, scan rate, interference, and calibration curve. The susceptible electrode's linear calibration curve encompassed concentration values between 8.88 and 1000.0 µM. The calculated limits of detection and quantification were 32.12 and 107.0 µM, respectively. Furthermore, this method was established in real human urine samples and drug validation which have been shown satisfactory results for vitamin B 6 detection., (© 2024. The Author(s).)

Breast cancer detection and differentiation of breast tissues are critical for accurate diagnosis and treatment planning. This study addresses the challenge of distinguishing between invasive ductal carcinoma (IDC), normal glandular breast tissues (nGBT), and adipose tissue using electrical impedance spectroscopy combined with Gaussian relaxation-time distribution (EIS-GRTD). The primary objective is to investigate the relaxation-time characteristics of these tissues and their potential to differentiate between normal and abnormal breast tissues. We applied a single-point EIS-GRTD measurement to ten mastectomy specimens across a frequency range f = 4 Hz to 5 MHz. The method calculates the differential ratio of the relaxation-time distribution functionΔγbetween IDC and nGBT, which is denoted byΔγIDC-nGBT,andΔγbetween IDC and adipose tissues, which is denoted byΔγIDC-adipose.As a result, the differential ratio ofΔγbetween IDC and nGBTΔγIDC-nGBTis 0.36, and between IDC and adiposeΔγIDC-adiposeis 0.27, which included in theα-dispersion atτpeak1=0.033±0.001s.In all specimens, the relaxation-time distribution functionγof IDCγIDCis higher, and there is no intersection withγof nGBTγnGBTand adiposeγadipose.The difference inγsuggests potential variations in relaxation properties at the molecular or structural level within each breast tissue that contribute to the overall relaxation response. The average mean percentage errorδfor IDC, nGBT, and adipose tissues are 5.90%, 6.33%, and 8.07%, respectively, demonstrating the model's accuracy and reliability. This study provides novel insights into the use of relaxation-time characteristic for differentiating breast tissue types, offering potential advancements in diagnosis methods. Future research will focus on correlating EIS-GRTD finding with pathological results from the same test sites to further validate the method's efficacy., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

This study presented a new method to design a MIP-based electrochemical sensor that could improve the selective and sensitive detection of ipratropium bromide (IPR). The polymeric film was designed using 2-hydroxyethyl methacrylate (HEMA) as the basic monomer, 2-hydroxy-2-methylpropiophenone as the initiator, ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and N-methacryloyl-L-aspartic acid (MAAsp) as the functional monomer. The presence of MAAsp results in the functional groups in imprinting binding sites, while the presence of poly(vinyl alcohol) (PVA) allows the generation of porous materials not only for sensitive sensing but also for avoiding electron transport limitations. Electrochemical characterizations of the changes at each stage of the MIP preparation process were confirmed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). In addition, morphological characterizations of the developed sensor were performed using scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurements. Theoretical calculations were also performed to explain/confirm the experimental results better. It was found that the results of the calculations using the DFT approach agreed with the experimental data. The MAAsp-IPR@MIP/GCE sensor was developed using the photopolymerization method, and the sensor surface was obtained by exposure to UV lamp radiation at 365 nm. The improved MIP-based electrochemical sensor demonstrated the ability to measure IPR for standard solutions in the linear operating range of 1.0 × 10 -12 -1.0 × 10 -11 M under optimized conditions. For standard solutions, the limit of detection (LOD) and limit of quantification (LOQ) were obtained as 2.78 × 10 -13 and 9.27 × 10 -13 M, respectively. The IPR recovery values for the inhalation form were calculated as 101.70 % and 100.34 %, and the mean relative standard deviations (RSD) were less than 0.76 % in both cases. In addition, the proposed modified sensor demonstrated remarkable sensitivity and selectivity for rapid assessment of IPR in inhalation forms. The sensor's unique selectivity is demonstrated by its successful performance even in the presence of IPR impurities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Catheter-based embolization has become a widely adopted minimally-invasive treatment for a broad range of applications. However, assessment of embolization endpoints requires x-ray fluoroscopic monitoring, exposing patients and physicians performing embolization procedures to harmful ionizing radiation. Moreover, x-ray fluoroscopy assessment of embolization endpoints is low sensitivity, subjective, and may not reflect the actual physiology of blood flow reduction, thus providing little oversight of the embolization procedure. Inspired by the observation that the dielectric properties of blood differ from those of fluids injected during the embolization procedure, a customized angiographic catheter was created with embedded electrodes for catheter-based electrochemical impedance spectroscopy as a way to monitor embolization. Real-time electrochemical impedance spectroscopy was performed in a phantom and compared to visual and videographic monitoring. Electrochemical impedance spectroscopy was able to sense endpoints of embolization, including stasis, reflux, and persistent flow. This new technique offers a label-free method of sensing embolization progress with potentially higher sensitivity and reproducibility compared to x-ray, as well as offer substantial reduction in x-ray exposure to patients and physicians., (© 2024. The Author(s).)

Background: Cutaneous melanoma (CM) is associated with a higher mortality rate than most other skin cancers. The purpose of this expert consensus panel was to review the published literature on new technological advancements for the diagnosis and prognosis for CM and provide updated guidance on their usage., Methods: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the topics of non-invasive diagnostic and prognostic testing for CM, including gene expression profiling (GEP) and electrical impedance spectroscopy (EIS). A panel of 10 dermatologists with significant expertise in the treatment of CM gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using widely recognized Strength of Recommendation Taxonomy criteria., Results: The literature search produced 200 articles that met the criteria. A screening of the studies resulted in 19 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 5 of which were given a strength of "A", 1 of which was given a strength of "B," and 1 of which was given a strength of "C"., Conclusion: The 2-GEP test and EIS can aid in the precise diagnosis of clinically indeterminate lesions and the 23-GEP test can be used when histopathology is equivocal. The 31-GEP test can enhance prognostic assessment beyond AJCC8 staging and improve clinical decision-making. J Drugs Dermatol. 2024;23(9):774-781. doi:10.36849/JDD.8365R1.

Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers - the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non-invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full-thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

This manuscript describes a novel methodology for studying relaxation dynamics in tissues and cells using characteristic frequency of bioimpedance spectroscopy measurements. The Bioimpedance Formalism allows for the simultaneous study of bioelectrical parameters in the frequency and time domains, providing insight into possible relaxation processes occurring in the tissue or cell of interest. Results from the Cole-Cole analysis showed no multiple relaxation processes associated with heterogeneity, with a visible age group separation in males compared with females. The study of the relaxation dynamic in the time domain revealed that the β parameter can be used to analyse the charge carriers in tissues, cells, or cancer cells, potentially leading to new diagnostic and therapeutic approaches for cancer and other diseases. Overall, this approach presents a promising area of research for gaining insights into the electrical properties of tissues and cells using bioimpedance methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Milk somatic cell count (SCC) is an international standard for identifying mastitis in dairy cows and measuring raw milk quality. Milk SCC can be predicted based on dielectric relaxation parameters (DRPs). We noted a high correlation between DRPs and the milk composition content (MCC), and so we hypothesized that combining DRPs with MCC could improve the prediction accuracy of milk SCC. The present study aimed to analyze the relationship between milk SCC, DRPs and MCC, as well as to investigate the potential of combining DRPs with MCC to improve the prediction accuracy of milk SCC., Results: The dielectric spectra (20-4500 MHz) of 276 milk samples were measured, and their DRPs (ε l , ε h , Δε, τ and σ) were solved by the modified Debye equation. The SCC prediction models were developed using dielectric full spectra, DRPs and DRPs combined with MCC. The results showed the correlations between DRPs (ε l , ε h , Δε and σ) and MCC (fat, protein, lactose and total solids) were high, and SCC exhibited a non-linear relationship with DRPs and MCC. The 5DRPs + MCC-generalized regression neural network model had the best prediction, with a standard error of prediction for prediction of 0.143 log SCC mL -1 and residual of the prediction bias of 2.870, which was superior to the models based on full spectra, DRPs and near-infrared or visible/near-infrared., Conclusion: The present study has improved the prediction accuracy of milk SCC based on the DRPs combing MCC and provides a new method for dairy farming and milk quality assessment. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

This article reports on a bioanalytical sensor device that hosts three different transducer principles: impedance spectroscopy, quartz-crystal microbalance with dissipation monitoring, and the thermal-current-based heat-transfer method. These principles utilize a single chip, allowing one to perform either microbalance and heat transfer measurements in parallel or heat transfer and impedance measurements. When taking specific precautions, the three measurement modalities can even be used truly simultaneously. The probed parameters are distinctly different, so that one may speak about multiparametric or "orthogonal" sensing without crosstalk between the sensing circuits. Hence, this sensor allows one to identify which of these label-free sensing principles performs best for a given bioanalytical application in terms of a high signal amplitude and signal-to-noise ratio. As a proof-of-concept, the three-parameter sensor was validated by studying the spontaneous, collective detachment of eukaryotic cells in the presence of a temperature gradient between the QCM chip and the supernatant liquid. In addition to heat transfer, detachment can also be monitored by the impedance- and QCM-related signals. These features allow for the distinguishing between different yeast strains that differ in their flocculation genes, and the sensor device enables proliferation monitoring of yeast colonies over time.

The moisture content of pharmaceutical powders can significantly impact the physical and chemical properties of drug formulations, solubility, flowability, and stability. However, current technologies for measuring moisture content in pharmaceutical materials require extensive calibration processes, leading to poor consistency and a lack of speed. To address this challenge, this study explores the feasibility of using impedance spectroscopy to enable accurate, rapid testing of moisture content of pharmaceutical materials with minimal to zero calibration. By utilizing electrochemical impedance spectroscopy (EIS) signals, we identify a strong correlation between the electrical properties of the materials and varying moisture contents in pharmaceutical samples. Equivalent circuit modeling is employed to unravel the underlying mechanism, providing valuable insights into the sensitivity of impedance spectroscopy to moisture content variations. Furthermore, the study incorporates deep learning techniques utilizing a 1D convolutional neural network (1DCNN) model to effectively process the complex spectroscopy data. The proposed model achieved a notable predictive accuracy with an average error of just 0.69% in moisture content estimation. This method serves as a pioneering study in using deep learning to provide a reliable solution for real-time moisture content monitoring, with potential applications extending from pharmaceuticals to the food, energy, environmental, and healthcare sectors.

Several medical techniques are based on the application of electromagnetic fields (EMFs) on the human body with therapeutic and/or diagnostic aims. The response of human tissues to the applied EMF is mediated by the tissues' dielectric properties, which must therefore be characterized at the frequencies of the considered technique. Due to the heterogeneity and complexity of biological tissues, it is necessary to know their properties in vivo for the specific condition of interest. Traditional techniques for the dielectric characterization of biological tissues are invasive and, as such, not adoptable for this aim. Accordingly, alternative sensors and/or sensing methods are needed. Recently, a new wideband spectroscopy technique was proposed, based on quantities derived from the Magnetic Resonance (MRI) signal. Among these quantities, the water content was proposed to evaluate the dielectric properties at frequencies around a few GHz. This work verifies the possibility of deriving tissues' dielectric properties in the frequency range of 1-20 GHz based on knowledge of the water content. The water content was retrieved through a dehydration procedure for five different ex vivo tissues. The achieved results were compared with references from the literature.

Objective. Producing realistic numerical models of neurostimulation electrodes in contact with the electrolyte and tissue, for use in time-domain finite element method simulations while maintaining a reasonable computational burden remains a challenge. We aim to provide a straightforward experimental-theoretical hybrid approach for common electrode materials (Ti, TiN, ITO, Au, Pt, IrOx) that are relevant to the research field of bioelectronics, along with all the information necessary to replicate our approach in arbitrary geometry for real-life experimental applications. Approach. We used electrochemical impedance spectroscopy (EIS) to extract the electrode parameters in the AC regime under different DC biases. The pulsed electrode response was obtained by fast amperometry (FA) to optimize and verify the previously obtained electrode parameters in a COMSOL Multiphysics model. For optimization of the electrode parameters a constant phase element (CPE) needed to be implemented in time-domain. Main results. We find that the parameters obtained by EIS can be used to accurately simulate pulsed response only close to the electrode open circuit potential, while at other potentials we give corrections to the obtained parameters, based on FA measurements. We also find that for many electrodes (Au, TiN, Pt, and IrOx), it is important to implement a distributed CPE rather than an ideal capacitor for estimating the electrode double-layer capacitance. We outline and provide examples for the novel time-domain implementation of the CPE for finite element method simulations in COMSOL Multiphysics. Significance. An overview of electrode parameters for some common electrode materials can be a valuable and useful tool in numerical bioelectronics models. A provided FEM implementation model can be readily adapted to arbitrary electrode geometries and used for various applications. Finally, the presented methodology for parametrization of electrode materials can be used for any materials of interest which were not covered by this work., (Creative Commons Attribution license.)

One of the most promising approaches to food quality assessments is the use of impedance spectroscopy combined with machine learning. Thereby, feature selection is decisive for a high classification accuracy. Physically based features have particularly significant advantages because they are able to consider prior knowledge and to concentrate the data into pertinent understandable information, building a solid basis for classification. In this study, we aim to identify physically based measurable features for muscle type and freshness classifications of bovine meat based on impedance spectroscopy measurements. We carry out a combined study where features are ranked based on their F1-score, cumulative feature selection, and t-distributed Stochastic Neighbor Embedding (t-SNE). In terms of features, we analyze the characteristic points (CPs) of the impedance spectrum and the model parameters (MPs) obtained by fitting a physical model to the measurements. The results show that either MPs or CPs alone are sufficient for detecting muscle type. Combining capacitance (C) and extracellular resistance (Rex) or the modulus of the characteristic point Z1 and the phase at the characteristic frequency of the beta dispersion (Phi2) leads to accurate separation. In contrast, the detection of freshness is more challenging. It requires more distinct features. We achieved a 90% freshness separation using the MPs describing intracellular resistance (Rin) and capacitance (C). A 95.5% freshness separation was achieved by considering the phase at the end of the beta dispersion (Phi3) and Rin. Including additional features related to muscle type improves the separability of samples; ultimately, a 99.6% separation can be achieved by selecting the appropriate features.

Measurement of endothelial and epithelial barrier integrity is important for a variety of in vitro models, including Transwell assays, cocultures, and organ-on-chip platforms. Barrier resistance is typically measured by trans-endothelial electrical resistance (TEER), but TEER is invasive and cannot accurately measure isolated monolayer resistance in coculture or most organ-on-chip devices. These limitations are addressed by porous membrane electrical cell-substrate impedance sensing (PM-ECIS), which measures barrier integrity in cell monolayers grown directly on permeable membranes patterned with electrodes. Here, we advanced the design and utility of PM-ECIS by investigating its sensitivity to working electrode size and correlation with TEER. Gold electrodes were fabricated on porous membrane inserts using hot embossing and UV lithography, with working electrode diameters of 250, 500, and 750 μm within the same insert. Sensitivity to resistance changes (4 kHz) during endothelial barrier formation was inversely proportional to electrode size, with the smallest being the most sensitive ( p < 0.001). Similarly, smaller electrodes were most sensitive to changes in impedance (40 kHz) corresponding to cell spreading and proliferation ( p < 0.001). Barrier disruption with both EGTA and thrombin was detectable by all electrode sizes. Resistances measured by PM-ECIS vs TEER for sodium chloride solutions were positively and significantly correlated for all electrode sizes ( r > 0.9; p < 0.0001), but only with 750 μm electrodes for endothelial monolayers ( r = 0.71; p = 0.058). These data inform the design and selection of PM-ECIS electrodes for specific applications and support PM-ECIS as a promising alternative to conventional TEER for direct, noninvasive, real-time assessment of cells cultured on porous membranes in conventional and organ-on-chip barrier models.

Management of obesity requires a multidisciplinary approach including physical activity interventions, which have significant impacts on overall health outcomes. Greater levels of lean muscle mass are significantly associated with improved health and reduced risk of comorbidities and should be preserved where possible when undertaking rapid weight loss. This article reports on the physical and functional outcomes achieved during a 12-week intensive multidisciplinary intervention targeting obesity and evaluates correlations between body composition and functional outcomes. We additionally aimed to investigate the test-retest reliability and levels of agreement in body composition measurements using bioimpedance spectroscopy between seated and standing positions. Of the 35 participants included in analysis, significant differences were observed between baseline and post-intervention measures. These included weight loss of 12.6 kg, waist circumference reduction of 10.5 cm, fat mass reduction by 2.9%, muscle mass increase by 1.6%, 54.5 m improvement in the 6-minute walk test and 3.8 rep improvement in the 30-second sit-to-stand test. No significant correlations were observed between physical and functional outcome measures. Excellent test re-test reliability was observed in bioimpedance spectroscopy seated measurements (ICC >.9). Significant differences were observed between seated and standing bioimpedance spectroscopy measurements, however they are regarded as small differences in a clinical setting., (© 2024 World Obesity Federation.)

Astract: One of the most common oral diseases affecting millions of people worldwide is periodontitis. Usually, proteins in body fluids are used as biomarkers of diseases. This study focused on hydrogen peroxide, lipopolysaccharide (LPS), and lactic acid as salivary non-protein biomarkers for oxidative stress conditions of periodontitis. Electrochemical analysis of artificial saliva was done using Gamry with increasing hydrogen peroxide, bLPS, and lactic acid concentrations. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were conducted. From EIS data, change in capacitance and CV plot area were calculated for each test condition. Hydrogen peroxide groups had a decrease in CV area and an increase in percentage change in capacitance, lipopolysaccharide groups had a decrease in CV area and a decrease in percentage change in capacitance, and lactic acid groups had an increase of CV area and an increase in percentage change in capacitance with increasing concentrations. These data showed a unique combination of electrochemical properties for the three biomarkers. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) employed to observe the change in the electrode surface and elemental composition data present on the sensor surface also showed a unique trend of elemental weight percentages. Machine learning models using hydrogen peroxide, LPS, and lactic acid electrochemical data were applied for the prediction of risk levels of periodontitis. The detection of hydrogen peroxide, LPS, and lactic acid by electrochemical biosensors indicates the potential to use these molecules as electrochemical biomarkers and use the data for ML-driven prediction tool for the periodontitis risk levels., (© 2024. International Federation for Medical and Biological Engineering.)

Modern medicine has increased the human lifespan. However, with an increase in average lifespan risk of amyloidosis increases. Amyloidosis is a condition characterized by protein misfolding and aggregation. Early detection of amyloidosis is crucial, yet conventional diagnostic methods are costly and lack precision, necessitating innovative tools. This review explores recent advancements in diverse amyloid detection methodologies, highlighting the need for interdisciplinary research to develop a miniaturized electrochemical biosensor leveraging nanotechnology. However, the diagnostics industry faces obstacles such as skilled labor shortages, standardized selection processes, and concurrent multi-analyte identification challenges. Research efforts are focused on integrating electrochemical techniques into clinical applications and diagnostics, with the successful transition of miniaturized technologies from development to testing posing a significant hurdle. Label-free transduction techniques like voltammetry and electrochemical impedance spectroscopy (EIS) have gained traction due to their rapid, cost-effective, and user-friendly nature., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Detecting chronic autoimmune disorders (ADs) early reduces the risk of morbidity, disability, and mortality and offers the possibility of significant therapeutic action in a timely manner. Developing low-cost, reliable, and sensitive sensors for ADs can ensure the efficient utilization of healthcare resources at earlier stages. Here, we report on the development of an electrochemical biosensor for sensing CXCL10, a chemokine protein that serves as a biomarker for autoimmune diseases. A self-assembly strategy is used for the immobilization of biorecognition elements on a plastic chip electrode (PCE). A homemade PCE offers a versatile and cost-effective scaffold for sensing applications. Gold nanoparticles were electrochemically deposited on the electrode via the reduction of gold ions on the PCE galvanostatically. The CXCL10 antibody and recognition elements were immobilized on the gold-deposited PCE. The attachment of recognition molecules was confirmed by energy-dispersive scanning electron microscopy, atomic force microscopy, infrared spectroscopy, and electrochemical techniques. Electrochemical impedance spectroscopy (EIS) was used for the detection of CXCL10 within a concentration range spanning from pico- to micro-molar levels. The sensor exhibited remarkable linearity in both buffer and plasma solutions, with a limit of detection (LOD) of up to 0.72 pg mL -1 .

The traditional methods in early caries detection had many limitations. So, this study aimed to evaluate the clinical performance of alternating current impedance spectroscopy ACIST in comparison with digital radiograph and ICDAS-II in detection of occlusal carious lesions. Occlusal surfaces of molar and premolar teeth from 40 adult participants were examined by two observers using three diagnostic methods: (1) international caries detection and assessment system (ICDAS-II) (2) digital radiograph (DR) and (3) Cariescan Pro device (ACIST). Agreement analysis and the difference in sensitivities and specificities were evaluated. The results showed an excellent agreement in the different groups. The difference from the visual tactile against ACIST scoring for enamel caries detection, was statistically significant (p = 0.012) and the agreement was moderate (k = 0.509). For dentinal caries the difference was not statistically significant (p > 0.05) and the agreement was similarly moderate (k < 0.6). The difference from the digital radiograph against ACIST scoring, for enamel caries, digital radiography had significantly higher sensitivity and specificity than ACIST (p < 0.001) while for dentinal caries detection and overall, ACIST had higher sensitivity and digital radiography had higher specificity and the difference was statistically significant (p < 0.001). Visual-tactile examination is a considered as feasible and valid technique for occlusal caries detection, digital radiography is superior to ACIST in diagnosing enamel caries, but it could underestimate the caries depth, ACIST is a reliable tool for detecting occlusal caries in dentin., (© 2024. The Author(s).)

Muscle dysfunction and muscle atrophy are common complications resulting from Chronic Obstructive Pulmonary Disease (COPD). The evaluation of the peripheral muscles can be carried out through the assessment of their structural components from ultrasound images or their functional components through isometric and isotonic strength tests. This evaluation, performed mainly on the quadriceps muscle, is not only of great interest for diagnosis, prognosis and monitoring of COPD, but also for the evaluation of the benefits of therapeutic interventions. In this work, bioimpedance spectroscopy technology is proposed as a low-cost and easy-to-use alternative for the evaluation of peripheral muscles, becoming a feasible alternative to ultrasound images and strength tests for their application in routine clinical practice. For this purpose, a laboratory prototype of a bioimpedance device has been adapted to perform segmental measurements in the quadriceps region. The validation results obtained in a pseudo-randomized study in patients with COPD in a controlled clinical environment which involved 33 volunteers confirm the correlation and correspondence of the bioimpedance parameters with respect to the structural and functional parameters of the quadriceps muscle, making it possible to propose a set of prediction equations. The main contribution of this manuscript is the discovery of a linear relationship between quadriceps muscle properties and the bioimpedance Cole model parameters, reaching a correlation of 0.69 and an average error of less than 0.2 cm regarding the thickness of the quadriceps estimations from ultrasound images, and a correlation of 0.77 and an average error of 3.9 kg regarding the isometric strength of the quadriceps muscle.

Bioimpedance spectrum (BIS) measurements have a great future in in vitro experiments, meeting all the requirements for non-destructive and label-free methods. Nevertheless, a real basic research can provide the necessary milestones to achieve the success of the method. In this paper a self-developed technology-based approach for in vitro assays is proposed. Authors invented a special graphene-based measuring plate in order to assess the high sensitivity and reproducibility of introduced technique. The design of the self-produced BIS plates maximizes the detection capacity of qualitative changes in cell culture and it is robust against physical effects and artifacts. The plates do not influence the viability and proliferation, however the results are robust, stable and reproducible regardless of when and where the experiments are carried out. In this study, physiological saline concentrations, two cancer and stem cell lines were utilized. All the results were statistically tested and confirmed. The findings of the assays show, that the introduced BIS technology is appropriate to be used in vitro experiments with high efficacy. The experimental results demonstrate high correlation values across the replicates, and the model parameters suggested that the characteristic differences among the various cell lines can be detected using appropriate hypothesis tests., (© 2024. The Author(s).)

Bioimpedance is a diagnostic sensing method used in medical applications, ranging from body composition assessment to detecting skin cancer. Commonly, discrete-component (and at times integrated) circuit variants of the Howland Current Source (HCS) topology are employed for injection of an AC current. Ideally, its amplitude should remain within 1% of its nominal value across a frequency range, and that nominal value should be programmable. However, the method's applicability and accuracy are hindered due to the current amplitude diminishing at frequencies above 100 kHz, with very few designs accomplishing 1 MHz, and only at a single nominal amplitude. This paper presents the design and implementation of an adaptive current source for bioimpedance applications employing automatic gain control (AGC). The "Adaptive Howland Current Source" (AHCS) was experimentally tested, and the results indicate that the design can achieve less than 1% amplitude error for both 1 mA and 100 µA currents for bandwidths up to 3 MHz. Simulations also indicate that the system can be designed to achieve up to 19% noise reduction relative to the most common HCS design. AHCS addresses the need for high bandwidth AC current sources in bioimpedance spectroscopy, offering automatic output current compensation without constant recalibration. The novel structure of AHCS proves crucial in applications requiring higher β-dispersion frequencies exceeding 1 MHz, where greater penetration depths and better cell status assessment can be achieved, e.g., in the detection of skin or breast cancer.

The food industry has grown with the demands for new products and their authentication, which has not been accompanied by the area of analysis and quality control, thus requiring novel process analytical technologies for food processes. An electronic tongue (e-tongue) is a multisensor system that can characterize complex liquids in a fast and simple way. Here, we tested the efficacy of an impedimetric microfluidic e-tongue setup - comprised by four interdigitated electrodes (IDE) on a printed circuit board (PCB), with four pairs of digits each, being one bare sensor and three coated with different ultrathin nanostructured films with different electrical properties - in the analysis of fresh and industrialized coconut water. Principal Component Analysis (PCA) was applied to observe sample differences, and Partial Least Squares Regression (PLSR) was used to predict sample physicochemical parameters. Linear Discriminant Analysis (LDA) and Partial Least Square - Discriminant Analysis (PLS-DA) were compared to classify samples based on data from the e-tongue device. Results indicate the potential application of the microfluidic e-tongue in the identification of coconut water composition and determination of physicochemical attributes, allowing for classification of samples according to soluble solid content (SSC) and total titratable acidity (TTA) with over 90% accuracy. It was also demonstrated that the microfluidic setup has potential application in the food industry for quality assessment of complex liquid samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ovarian cancer (OC) has the highest mortality rate among malignant tumors, primarily because it is difficult to diagnose early. Exosomes, a type of extracellular vesicle rich in parental information, have garnered significant attention in the field of cancer diagnosis and treatment. They play an important regulatory role in the occurrence, development, and metastasis of OC. Consequently, exosomes have emerged as noninvasive biomarkers for early cancer detection. Therefore, identifying cancer-derived exosomes may offer a novel biomarker for the early detection of OC. In this study, we developed a metal-organic frameworks assembled "double hook"-type aptamer electrochemical sensor, which enables accurate early diagnosis of OC. Under optimal experimental conditions, electrochemical impedance spectroscopy technology demonstrated a good linear relationship within the concentration range of 31-3.1 × 10 6 particles per microliter, with a detection limit as low as 12 particles per microliter. The universal exosome detection platform is constructed, and this platform can not only differentiate between high-grade serous ovarian cancer (HGSOC) patients and healthy individuals but also distinguish between HGSOC patients and nonhigh-grade serous OC (non-HGSOC). Consequently, it provides a novel strategy for the early diagnosis of OC and holds great significance in clinical differential diagnosis.

This paper reports a rapid and sensitive sensor for the detection and quantification of the COVID-19 N-protein (N-PROT) via an electrochemical mechanism. Single-frequency electrochemical impedance spectroscopy was used as a transduction method for real-time measurement of the N-PROT in an immunosensor system based on gold-conjugate-modified carbon screen-printed electrodes (Cov-Ag-SPE). The system presents high selectivity attained through an optimal stimulation signal composed of a 0.0 V DC potential and 10 mV RMS -1 AC signal at 100 Hz over 300 s. The Cov-Ag-SPE showed a log response toward N-PROT detection at concentrations from 1.0 ng mL -1 to 10.0 μg mL -1 , with a 0.977 correlation coefficient for the phase (θ) variation. An ML-based approach could be created using some aspects observed from the positive and negative samples; hence, it was possible to classify 252 samples, reaching 83.0, 96.2 and 91.3% sensitivity, specificity, and accuracy, respectively, with confidence intervals (CI) ranging from 73.0 to 100.0%. Because impedance spectroscopy measurements can be performed with low-cost portable instruments, the immunosensor proposed here can be applied in point-of-care diagnostics for mass testing, even in places with limited resources, as an alternative to the common diagnostics methods.

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer, predominantly affecting patients with chronic liver diseases such as hepatitis B or C-induced cirrhosis. Diagnosis typically involves blood tests (assessing liver functions and HCC biomarkers), imaging procedures such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), and liver biopsies requiring the removal of liver tissue for laboratory analysis. However, these diagnostic methods either entail lengthy lab processes, require expensive imaging equipment, or involve invasive techniques like liver biopsies. Hence, there exists a crucial need for rapid, cost-effective, and noninvasive techniques to characterize HCC, whether in serum or tissue samples. In this study, we developed a spiral sensor implemented on a printed circuit board (PCB) technology that utilizes impedance spectroscopy and applied it to 24 tissues and sera samples as proof of concept. This newly devised circuit has successfully characterized HCC and normal tissue and serum samples. Utilizing the distinct dielectric properties between HCC cells and serum samples versus the normal samples across a specific frequency range, the differentiation between normal and HCC samples is achieved. Moreover, the sensor effectively characterizes two HCC grades and distinguishes cirrhotic/non-cirrhotic samples from tissue specimens. In addition, the sensor distinguishes cirrhotic/non-cirrhotic samples from serum specimens. This pioneering study introduces Electrical Impedance Spectroscopy (EIS) spiral sensor for diagnosing HCC and liver cirrhosis in clinical serum-an innovative, low-cost, rapid (< 2 min), and precise PCB-based technology without elaborate sample preparation, offering a novel non-labeled screening approach for disease staging and liver conditions., (© 2024. The Author(s).)

Heart failure is a severe medical condition with an important worldwide incidence that occurs when the heart is unable to efficiently pump the patient's blood throughout the body. The monitoring of edema in the lower limbs is one of the most efficient ways to control the evolution of the condition. Impedance spectroscopy has been proposed as an efficient technique to monitor body volume in patients with heart failure. It is necessary to research new wearable devices for remote patient monitoring, which can be easily worn by patients in a continuous way. In this work, we design and implement new wearable textile electrodes for the monitoring of edema evolution in patients with heart failure. Impedance spectroscopy measurements were carried out in 5 healthy controls and 2 patients with heart failure using our wearable electrodes for 3 days. The results show the appropriateness of impedance spectroscopy and our wearable electrodes to monitor body volume evolution. Impedance spectroscopy is shown to be an efficient marker of the presence of edema in heart failure patients. Initial patient positive feedback was obtained for the use of the wearable device.

Mastitis diagnosis can be made by detecting Staphylococcus aureus (S. aureus), which requires high sensitivity and selectivity. Here, we report on microfluidic genosensors and electronic tongues to detect S. aureus DNA using impedance spectroscopy with data analysis employing visual analytics and machine learning techniques. The genosensors were made with layer-by-layer films containing either 10 bilayers of chitosan/chondroitin sulfate or 8 bilayers of chitosan/sericin functionalized with an active layer of cpDNA S. aureus. The specific interactions leading to hybridization in these genosensors allowed for a low limit of detection of 5.90 × 10 -19  mol/L. The electronic tongue had four sensing units made with 6-bilayer chitosan/chondroitin sulfate films, 10-bilayer chitosan/chondroitin sulfate, 8-bilayer chitosan/sericin, and 8-bilayer chitosan/gold nanoparticles modified with sericin. Despite the absence of specific interactions, various concentrations of DNA S. aureus could be distinguished when the impedance data were plotted using a dimensionality reduction technique. Selectivity of S. aureus DNA was confirmed using multidimensional calibration spaces, based on machine learning, with accuracy up to 89 % for the genosensors and 66 % for the electronic tongue. Hence, with these computational methods one may opt for the more expensive genosensors or the simpler and cheaper electronic tongue, depending on the sensitivity level required to diagnose mastitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Distinguishing quiescent from rupture-prone atherosclerotic lesions has significant translational and clinical implications. Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies. We evaluated invasive 6-point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology. Male New Zealand White rabbits (n = 16) were placed on a high-fat diet, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwent in vivo micro-PET imaging of the abdominal aorta with 68 Ga-DOTATATE, 18 F-NaF, and 18 F-FDG, followed by invasive interrogation via IVUS and EIS. Background signal-corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histology. Analyses were performed blindly. EIS impedance was associated with markers of plaque activity including macrophage infiltration (r = .813, p = .008) and macrophage/smooth muscle cell (SMC) ratio (r = .813, p = .026). Moreover, EIS phase delay correlated with anatomic markers of plaque burden, namely intima/media ratio (r = .883, p = .004) and %stenosis (r = .901, p = .002), similar to IVUS. 68 Ga-DOTATATE correlated with intimal macrophage infiltration (r = .861, p = .003) and macrophage/SMC ratio (r = .831, p = .021), 18 F-NaF with SMC infiltration (r = -.842, p = .018), and 18 F-FDG correlated with macrophage/SMC ratio (r = .787, p = .036). EIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non-invasive imaging approaches to capture. These findings indicate the potential of invasive EIS to comprehensively evaluate human coronary artery disease., (© 2024 Federation of American Societies for Experimental Biology.)

Malaria is a disease that affects millions of people worldwide, particularly in developing countries. The development of accurate and efficient methods for the detection of malaria-infected cells is crucial for effective disease management and control. This paper presents the electrical impedance spectroscopy (EIS) of normal and malaria-infected red blood cells. An EIS microfluidic device, comprising a microchannel and a pair of coplanar electrodes, was fabricated for single-cell measurements in a continuous manner. Based on the EIS results, the aim of this work is to discriminate Plasmodium falciparum -infected red blood cells from the normal ones. Different from typical impedance spectroscopy, our measurement was performed for the cells in a low-conductivity medium in a frequency range between 50 kHz and 800 kHz. Numerical simulation was utilized to study the suitability parameters of the microchannel and electrodes for the EIS experiment over the measurement frequencies. The measurement results have shown that by using the low-conductivity medium, we could focus on the change in the conductance caused by the presence of a cell in the sensing electrode gap. The results indicated a distinct frequency spectrum of the conductance between the normal and infected red blood cells, which can be further used for the detection of the disease.

Objective . Bioimpedance spectroscopy (BIS) is a popular technique for the assessment of body composition in children and adults but has not found extensive use in babies and infants. This due primarily to technical difficulties of measurement in these groups. Although improvements in data modelling have, in part, mitigated this issue, the problem continues to yield unacceptably high rates of poor quality data. This study investigated an alternative data modelling procedure obviating issues associated with BIS measurements in babies and infants. Approach. BIS data are conventionally analysed according to the Cole model describing the impedance response of body tissues to an appliedACcurrent. This approach is susceptible to errors due to capacitive leakage errors of measurement at high frequency. The alternative is to model BIS data based on the resistance-frequency spectrum rather than the reactance-resistance Cole model thereby avoiding capacitive error impacts upon reactance measurements. Main results. The resistance-frequency approach allowed analysis of 100% of data files obtained from BIS measurements in 72 babies compared to 87% successful analyses with the Cole model. Resistance-frequency modelling error (percentage standard error of the estimate) was half that of the Cole method. Estimated resistances at zero and infinite frequency were used to predict body composition. Resistance-based prediction of fat-free mass (FFM) exhibited a 30% improvement in the two-standard deviation limits of agreement with reference FFM measured by air displacement plethysmography when compared to Cole model-based predictions. Significance. This study has demonstrated improvement in the analysis of BIS data based on the resistance frequency response rather than conventional Cole modelling. This approach is recommended for use where BIS data are compromised by high frequency capacitive leakage errors such as those obtained in babies and infants., (Creative Commons Attribution license.)

The purpose of this study is to evaluate the intracellular and extracellular volume before and after anesthesia in order to ascertain their variations and determine the potential utility of this information in optimizing intraoperative fluid administration practices. A bioimpedance spectroscopy device (body composition monitor, BCM) was used to measure total body fluid volume, extracellular volume, and intracellular volume. BCM measurements were performed before and after general anesthesia in unselected healthy children and adolescents visiting the Pediatric Institute of Southern Switzerland for low-risk surgical procedures hydrated with an isotonic solution. In 100 children and adolescents aged 7.0 (4.8-11) years (median and interquartile range), the average total body water increased perioperatively with a delta value of 182 (0-383) mL/m 2 from pre- to postoperatively, as well as the extracellular water content, which had a similar increase with a delta value of 169 (19-307) mL/m 2 . The changes in total body water and extracellular water content significantly correlated with the amount of fluids administered. The intracellular water content did not significantly change.   Conclusion: Intraoperative administration of isotonic solutions results in a significant fluid accumulation in low-risk schoolchildren during general anesthesia. The results suggest that children without major health problems undergoing short procedures do not need any perioperative intravenous fluid therapy, because they are allowed to take clear fluids up to 1 h prior anesthesia. In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy. What is Known: • Most children who undergo common surgical interventions or investigations requiring anesthesia are nowadays hydrated at a rate of 1700 mL/m 2 /day with an isotonic solution. • The use bioimpedance spectroscopy for the assessment of fluid status in healthy children has already been successfully validated. • The bioimpedance spectroscopy is already currently widely used in various nephrological settings to calculate fluid overload and determine patient's optimal fluid status. What is New: • Routine intraoperative fluid administration results in a significant fluid accumulation during general anesthesia in low-risk surgical procedures. • This observation might be relevant for children and adolescents with conditions predisposing to fluid retention. • In future studies, the use of BCM measurements has the potential to be valuable in guiding intraoperative fluid therapy., (© 2024. The Author(s).)

The most reliable methods for pregnancy diagnosis in dairy herds include rectal palpation, ultrasound examination, and evaluation of plasma progesterone concentrations. However, these methods are expensive, labor-intensive, and invasive. Thus, there is a need to develop a practical, non-invasive, cost-effective method that can be implemented on the farm to detect pregnancy. This study suggests employing microwave dielectric spectroscopy (MDS, 0.5-40 GHz) as a method to evaluate reproduction events in dairy cows. The approach involves the integration of MDS data with information on milk solids to detect pregnancy and identify early embryonic loss in dairy cows. To test the ability to predict pregnancy according to these measurements, milk samples were collected from (i) pregnant and non-pregnant randomly selected cows, (ii) weekly from selected cows ( n = 12) before insemination until a positive pregnancy test, and (iii) daily from selected cows ( n = 10) prior to insemination until a positive pregnancy test. The results indicated that the dielectric strength of Δ ε and the relaxation time, τ , exhibited reduced variability in the case of a positive pregnancy diagnosis. Using principal component analysis (PCA), a clear distinction between pregnancy and nonpregnancy status was observed, with improved differentiation upon a higher sampling frequency. Additionally, a neural network machine learning technique was employed to develop a prediction algorithm with an accuracy of 73%. These findings demonstrate that MDS can be used to detect changes in milk upon pregnancy. The developed machine learning provides a broad classification that could be further enhanced with additional data.

The study presents a promising approach to enzymatic kinetics using Electrochemical Impedance Spectroscopy (EIS) to assess fundamental parameters of modified enteropeptidases. Traditional methods for determining these parameters, while effective, often lack versatility and convenience, especially under varying environmental conditions. The use of EIS provides a novel approach that overcomes these limitations. The enteropeptidase underwent genetic modification through the introduction of single amino acid modifications to assess their effect on enzyme kinetics. However, according to the one-sample t -test results, the difference between the engineered enzymes and hEKL was not statistically significant by conventional criteria. The kinetic parameters were analyzed using fluorescence spectroscopy and EIS, which was found to be an effective tool for the real-time measurement of enzyme kinetics. The results obtained through EIS were not significantly different from those obtained through traditional fluorescence spectroscopy methods ( p value >> 0.05). The study validates the use of EIS for measuring enzyme kinetics and provides insight into the effects of specific amino acid changes on enteropeptidase function. These findings have potential applications in biotechnology and biochemical research, suggesting a new method for rapidly assessing enzymatic activity.

Here, we present the results of our the electrochemical aptasensing strategy for retinol binding protein-4 (RBP-4) detection based on a thiolated aptamer against RBP-4 and 6-mercaptohexanol (MCH) directly immobilized on a gold electrode surface. The most important parameters affecting the magnitude of the analytical signal generated were optimized: (i) the presence of magnesium ions in the immobilization and measurement buffer, (ii) the concentration of aptamer in the immobilization solution and (iii) its folding procedure. In this work, a systematic assessment of the electrochemical parameters related to the optimization of the sensing layer of the aptasensor was carried out (electron transfer coefficients (α), electron transfer rate constants ( k 0 ) and surface coverage of the thiolated aptamer probe ( Γ Apt )). Then, under the optimized conditions, the analytical response towards RBP-4 protein, in the presence of an Fe(CN) 6 3-/4- redox couple in the supporting solution was assessed. The proposed electrochemical strategy allowed for RBP-4 detection in the concentration range between 100 and 1000 ng/mL with a limit of detection equal to 44 ng/mL based on electrochemical impedance spectroscopy (EIS). The specificity studies against other diabetes biomarkers, including vaspin and adiponectin, proved the selectivity of the proposed platform. These preliminary results will be used in the next step to miniaturize and test the sensor in real samples.

Background: Bioimpedance spectroscopy (BIS) measurements are conventionally performed in supine position with a lead device attached to gel-backed electrodes, and more recently, with a stand-on device that uses fixed stainless-steel electrodes under the hands and feet. The aim of this study was to assess and compare BIS measurements made in supine, sitting, and standing positions using lead and stand-on impedance devices in participants with and without unilateral leg lymphedema. Materials and Methods: Participants with self-ascribed unilateral leg lymphedema ( n  = 24) and healthy controls ( n  = 71) were recruited using a cross-sectional study design. Triplicate BIS measurements were taken for each device in each position. Results: Impedance measurements with either device were reliable with coefficient of variation of 0.6% or lower. The magnitude of mean differences in absolute impedance values between devices were between 1% and 6% dependent on condition. L-Dex scores between the two devices were highly correlated ( r  = 0.82) and ∼70% of participants in the lymphedema group were classified as having lymphedema using the recommended cut-off with either device. There was no significant interleg difference of controls using the lead device; however, small, but significant differences ( p  = 0.0001) were found when using the stand-on device. Conclusion: The findings demonstrate that reliable impedance measurements of the legs can be made with either device in lying, sitting, or standing positions. However, data between the devices were not directly interchangeable. Although the risk of misidentification was small, reference ranges appropriate to the device and measurement position should be used when converting data to L-Dex scores.

Herein the development of cellular impedance biosensors, electrochemical impedance spectroscopy, and the general principles and terms associated with the cell-electrode interface is reviewed. This family of techniques provides quantitative and sensitive information into cell responses to stimuli in real-time with high temporal resolution. The applications of cell-based impedance biosensors as a readout in cell biology is illustrated with a diverse range of examples. The current state of the field, its limitations, the possible available solutions, and the potential benefits of developing biosensors are discussed.

Viable cell density (VCD) and cell viability (CV) are key performance indicators of cell culture processes in biopharmaceutical production of biologics and vaccines. Traditional methods for monitoring VCD and CV involve offline cell counting assays that are both labor intensive and prone to high variability, resulting in sparse sampling and uncertainty in the obtained data. Process analytical technology (PAT) approaches offer a means to address these challenges. Specifically, in situ probe-based measurements of dielectric spectroscopy (also commonly known as capacitance) can characterize VCD and CV continuously in real time throughout an entire process, enabling robust process characterization. In this work, we propose in situ dielectric spectroscopy as a PAT tool for real time analysis of live-virus vaccine (LVV) production. Dielectric spectroscopy was collected across 25 discreet frequencies, offering a thorough evaluation of the proposed technology. Correlation of this PAT methodology to traditional offline cell counting assays was performed, in which VCD and CV were both successfully predicted using dielectric spectroscopy. Both univariate and multivariate data analysis approaches were evaluated for their potential to establish correlation between the in situ dielectric spectroscopy and offline measurements. Univariate analysis strategies are presented for optimal single frequency selection. Multivariate analysis, in the form of partial least squares (PLS) regression, produced significantly higher correlations between dielectric spectroscopy and offline VCD and CV data, as compared to univariate analysis. Specifically, by leveraging multivariate analysis of dielectric information from all 25 spectroscopic frequencies measured, PLS models performed significantly better than univariate models. This is particularly evident during cell death, where tracking VCD and CV have historically presented the greatest challenge. The results of this work demonstrate the potential of both single and multiple frequency dielectric spectroscopy measurements for enabling robust LVV process characterization, suggesting that broader application of in situ dielectric spectroscopy as a PAT tool in LVV processes can provide significantly improved process understanding. To the best of our knowledge, this is the first report of in situ dielectric spectroscopy with multivariate analysis to successfully predict VCD and CV in real time during live virus-based vaccine production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)