Impedance measurement of a forearm with the Sciospec Medical Research ISX-3 impedance analyzer
The Medical Research ISX-3 impedance analyzer is intended to facilitate the use of impedance spectroscopy in medical research applications. To that end it includes measures for enhanced electrical safety including medical grade isolation enabling a safe operation of the instrument in medical research settings.
This very simple experiment shows the impedance change in the forearm due to a movement of the hand. The direct response in impedance is visible in the live-plotter of the data (absolute impedance and phase).
- Medical Research ISX-3 with a 32-channel multiplexer
- only 4 channels were used
- 4-point measurement
- Adhesive electrodes (ECG-electrodes) Ambu Bluesensor NF NF-50-A/12
512 channel system for in-depth insights into complex cell electrophysiology
Portable Impedance Analyzer for a mobile health application
CHARACTERIZATION OF THE ENCAPSULATION PROCESS OF DEEP BRAIN STIMULATION ELECTRODES USING IMPEDANCE SPECTROSCOPY IN A RODENT MODEL
Deep brain stimulation (DBS) is effective for the treatment of patients with Parkinson’s disease (PD), especially in advanced stages which are refractory to conventional therapy. Despite of the regular use in clinical therapy, rodent models for basic research into DBS are not routinely available. The main reason is the geometry difference from rodents to humans, imposing larger problems in the transfer of the stimulation conditions than from primates to humans. For rodents, the development of miniaturized mobile stimulators and stimulation parameters, as well as improved electrode materials and geometry are desirable. The impedance of custom made, cylindrical (contact diameter 200 µm, length 100 µm), platinum/iridium electrodes has been measured in vivo for two weeks to characterize the influence of electrochemical processes and of the adherent cell growth at the electrode surface. During the encapsulation process, the real
part of the electrode impedance at 10 kHz doubled with respect to its initial value after a characteristic decrease by approximately one third at the second day. An outlook is given on further investigations with different electrode designs for long-term DBS.
Electrical Impedance Properties of Deep Brain Stimulation Electrodes during Long-Term In-Vivo Stimulation in the Parkinson Model of the Rat
Deep brain stimulation (DBS) is an invasive therapeutic option for patients with Parkinson’s disease (PD) but the mechanisms behind it are not yet fully understood. Animal models are essential for basic DBS research, because cell based in-vitro techniques are not complex enough. However, the geometry difference between rodents and humans implicates transfer problems of the stimulation conditions. For rodents, the development of miniaturized mobile stimulators and adapted electrodes are desirable. We implanted uni- and bipolar platinum/iridium electrodes in rats and were able to establish chronical instrumentation of freely moving rats (3 weeks). We measured the impedance of unipolar electrodes in-vivo to characterize the influence of electrochemical processes at the electrode-tissue interface. During the encapsulation process, the real part of the electrode impedance at 10 kHz doubled after 12 days and increased almost 10 times after 22 days. An outlook is given on the quantification of the DBS effect by sensorimotor behavioral tests
A Novel 3D Label-Free Monitoring System of hES-Derived Cardiomyocyte Clusters: A Step Forward to In Vitro Cardiotoxicity Testing
Unexpected adverse effects on the cardiovascular system remain a major challenge in the development of novel active pharmaceutical ingredients (API). To overcome the current limitations of animal-based in vitro and in vivo test systems, stem cell derived human cardiomyocyte clusters (hCMC) offer the opportunity for highly predictable pre-clinical testing. The three-dimensional structure of hCMC appears more representative of tissue milieu than traditional monolayer cell culture. However, there is a lack of long-term, real time monitoring systems for tissue-like cardiac material. To address this issue, we have developed a microcavity array (MCA)-based label-free monitoring system that eliminates the need for critical hCMC adhesion and outgrowth steps. In contrast, feasible field potential derived action potential recording is possible immediately after positioning within the microcavity. Moreover, this approach allows extended observation of adverse effects on hCMC. For the first time, we describe herein the monitoring of hCMC over 35 days while preserving the hCMC structure and electrophysiological characteristics. Furthermore, we demonstrated the sensitive detection and quantification of adverse API effects using E4031, doxorubicin, and noradrenaline directly on unaltered 3D cultures. The MCA system provides multi-parameter analysis capabilities incorporating field potential recording, impedance spectroscopy, and optical read-outs on individual clusters giving a comprehensive insight into induced cellular alterations within a complex cardiac culture over days or even weeks.
Impedance-based detection of extracellular DNA in wounds
Wound infection status is a relevant diagnostic parameter to enhance wound treatment towards better healing rate. Impedance evaluation is a powerful tool to measure the inflammatory response like the released DNA of neutrophils. In our research we investigated the dielectric behaviour of neutrophils settled on electrodes in vitro. The cells have been stimulated to react in the same way as in a wound infection. The result is a significant impedance deviation of about 50 % with comparable amount of cells like in an infected wound. Microscopic fluorescence verifications acknowledge these findings.
Infection Monitoring in Wounds
Wound infection monitoring is a challenging task. It is only solvable by designing an integrable and cost-efficient sensor which measures a relevant set of parameters. One viable parameter is the formation of neutrophil extracellular traps (NETs). Their task is trapping pathogens in the wound. A wound infection results in massive release of them which can be detected with impedimetric methods. Our investigations focused on the characterization of the biological process with an in vitro model. The model environment is a cell culture with neutrophil granulocytes cultured on interdigitated electrodes which represent the sensor surface. Detected impedance changes caused by NET-formation were in the range of 35% and even higher. This implies that impedance measurements are suitable for NET detection. We derived a measurement and evaluated it by differing conditions like changing stimulation agent and varying the cell number. For both conditions the results of impedance and phase angle deviation can be confirmed. In combination with other parameters a sensor can be designed for specific detection of wound infections. These aspects are integrated in our sensor concept.
A novel 96-well multielectrode array based impedimetric monitoring platform for comparative drug efficacy analysis on 2D and 3D brain tumor cultures
Aggressive cancer entities like neuroblastoma and glioblastoma multiforme are still difficult to treat and have discouraging prognosis in malignant stage. Since each tumor has its own characteristics concerning the sensitivity towards different chemotherapeutics and moreover, can obtain resistance, the development of novel chemotherapeutics with a broad activity spectrum, high efficacy and minimum side effects is a continuous process. Sophisticated in vitro assays for comprehensive prediction of in vivo drug efficacy and side effects represent an actual bottleneck in the drug development process. In this context, we developed a novel in vitro 2D and 3D multiwell–multielectrode device for drug efficacy monitoring based on direct real-time impedance spectroscopy measurement in combination with our unique 96-well multielectrode arrays and microcavity arrays. For demonstration, we used three neuro- and glioblastoma cell lines that were cultured as monolayer and multicellular tumor spheroids for recapitulating in vivo conditions. Using our novel 96-well multielectrode array based system it was possible to detect time and concentration dependent responses concerning treatment with doxorubicin, etoposide and vincristine. While all tested chemotherapeutics revealed high potency for apoptosis induction in neuroblastoma cells, etoposide was ineffective for glioblastoma cell lines. Determination of IC50 values allowed us to compare drug efficacy in 2D and 3D culture models and moreover, revealed chemotherapeutic and tumor cell line specific activity patterns. These pharmacokinetic patterns are of great interest in the context of preclinical drug development. Thus, impedance spectroscopy based monitoring systems could be used for the fast in vitro based in vivo prediction of novel anti-tumor drugs.