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Lab on a Chip Mar 2022Electrode-based impedance and electrochemical measurements can provide cell-biology information that is difficult to obtain using optical-microscopy techniques. Such...
Electrode-based impedance and electrochemical measurements can provide cell-biology information that is difficult to obtain using optical-microscopy techniques. Such electrical methods are non-invasive, label-free, and continuous, eliminating the need for fluorescence reporters and overcoming optical imaging's throughput/temporal resolution limitations. Nonetheless, electrode-based techniques have not been heavily employed because devices typically contain few electrodes per well, resulting in noisy aggregate readouts. Complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs) have sometimes been used for electrophysiological measurements with thousands of electrodes per well at sub-cellular pitches, but only basic impedance mappings of cell attachment have been performed outside of electrophysiology. Here, we report on new field-based impedance mapping and electrochemical mapping/patterning techniques to expand CMOS-MEA cell-biology applications. The methods enable accurate measurement of cell attachment, growth/wound healing, cell-cell adhesion, metabolic state, and redox properties with single-cell spatial resolution (20 μm electrode pitch). These measurements allow the quantification of adhesion and metabolic differences of cells expressing oncogenes wild-type controls. The multi-parametric, cell-population statistics captured by the chip-scale integrated device opens up new avenues for fully electronic high-throughput live-cell assays for phenotypic screening and drug discovery applications.
Topics: Cell Culture Techniques; Electrophysiological Phenomena; Microelectrodes; Oxides; Semiconductors
PubMed: 35266462
DOI: 10.1039/d1lc00878a -
Scientific Reports Aug 2022Long-term implantable neural interfacing devices are able to diagnose, monitor, and treat many cardiac, neurological, retinal and hearing disorders through nerve...
Long-term implantable neural interfacing devices are able to diagnose, monitor, and treat many cardiac, neurological, retinal and hearing disorders through nerve stimulation, as well as sensing and recording electrical signals to and from neural tissue. To improve specificity, functionality, and performance of these devices, the electrodes and microelectrode arrays-that are the basis of most emerging devices-must be further miniaturized and must possess exceptional electrochemical performance and charge exchange characteristics with neural tissue. In this report, we show for the first time that the electrochemical performance of femtosecond-laser hierarchically-restructured electrodes can be tuned to yield unprecedented performance values that significantly exceed those reported in the literature, e.g. charge storage capacity and specific capacitance were shown to have improved by two orders of magnitude and over 700-fold, respectively, compared to un-restructured electrodes. Additionally, correlation amongst laser parameters, electrochemical performance and surface parameters of the electrodes was established, and while performance metrics exhibit a relatively consistent increasing behavior with laser parameters, surface parameters tend to follow a less predictable trend negating a direct relationship between these surface parameters and performance. To answer the question of what drives such performance and tunability, and whether the widely adopted reasoning of increased surface area and roughening of the electrodes are the key contributors to the observed increase in performance, cross-sectional analysis of the electrodes using focused ion beam shows, for the first time, the existence of subsurface features that may have contributed to the observed electrochemical performance enhancements. This report is the first time that such performance enhancement and tunability are reported for femtosecond-laser hierarchically-restructured electrodes for neural interfacing applications.
Topics: Cross-Sectional Studies; Electrodes; Electrodes, Implanted; Lasers; Microelectrodes; Nerve Tissue; Nervous System
PubMed: 35978090
DOI: 10.1038/s41598-022-18161-4 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Apr 2020As an interface between external electronic devices and internal neural nuclei, microelectrodes play an important role in many fields, such as animal robots, deep brain...
As an interface between external electronic devices and internal neural nuclei, microelectrodes play an important role in many fields, such as animal robots, deep brain stimulation and neural prostheses. Aiming at the problem of high price and complicated fabrication process of microelectrode, a microelectrode twisting machine based on open source electronic prototyping platform (Arduino) and three-dimensional printing technology was proposed, and its microelectrode fabrication performance and neural stimulation performance were verified. The results show that during the fabrication of microelectrodes, the number of positive twisting turns of the electrode wire should generally be set to about 1.8 times of its length, and the number of reverse twisting rings is independent of the length, generally about 5. Moreover, compared with the traditional instrument, the device is not only inexpensive and simple to manufacture, but also has good expandability. It has a positive significance for both the personalization and popularization of microelectrode fabrication and the reduction of experimental cost.
Topics: Equipment Design; Microelectrodes; Printing, Three-Dimensional
PubMed: 32329285
DOI: 10.7507/1001-5515.201908058 -
Frontiers in Neural Circuits 2022Cascading activity is commonly observed in complex dynamical systems, including networks of biological neurons, and how these cascades spread through the system is...
Cascading activity is commonly observed in complex dynamical systems, including networks of biological neurons, and how these cascades spread through the system is reliant on how the elements of the system are connected and organized. In this work, we studied networks of neurons as they matured over 50 days and evaluated both their dynamics and their functional connectivity structures by observing their electrophysiological activity using microelectrode array recordings. Correlations were obtained between features of their activity propagation and functional connectivity characteristics to elucidate the interplay between dynamics and structure. The results indicate that networks maintain a slightly subcritical state by striking a balance between integration and segregation. Our work demonstrates the complementarity of these two approaches-functional connectivity and avalanche dynamics-in studying information propagation in neurons , which can in turn inform the design and optimization of engineered computational substrates.
Topics: Microelectrodes; Nerve Net; Neurons
PubMed: 36188125
DOI: 10.3389/fncir.2022.980631 -
Journal of Neural Engineering Feb 2015To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the... (Review)
Review
To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.
Topics: Action Potentials; Brain; Brain-Computer Interfaces; Coated Materials, Biocompatible; Electrodes, Implanted; Electroencephalography; Equipment Design; Equipment Failure Analysis; Microelectrodes; Neurons
PubMed: 25460808
DOI: 10.1088/1741-2560/12/1/011001 -
Sensors (Basel, Switzerland) Mar 2019Microfabrication technology for cortical interfaces has advanced rapidly over the past few decades for electrophysiological studies and neuroprosthetic devices offering... (Review)
Review
Microfabrication technology for cortical interfaces has advanced rapidly over the past few decades for electrophysiological studies and neuroprosthetic devices offering the precise recording and stimulation of neural activity in the cortex. While various cortical microelectrode arrays have been extensively and successfully demonstrated in animal and clinical studies, there remains room for further improvement of the probe structure, materials, and fabrication technology, particularly for high-fidelity recording in chronic implantation. A variety of non-conventional probes featuring unique characteristics in their designs, materials and fabrication methods have been proposed to address the limitations of the conventional standard shank-type ("Utah-" or "Michigan-" type) devices. Such non-conventional probes include multi-sided arrays to avoid shielding and increase recording volumes, mesh- or thread-like arrays for minimized glial scarring and immune response, tube-type or cylindrical probes for three-dimensional (3D) recording and multi-modality, folded arrays for high conformability and 3D recording, self-softening or self-deployable probes for minimized tissue damage and extensions of the recording sites beyond gliosis, nanostructured probes to reduce the immune response, and cone-shaped electrodes for promoting tissue ingrowth and long-term recording stability. Herein, the recent progress with reference to the many different types of non-conventional arrays is reviewed while highlighting the challenges to be addressed and the microfabrication techniques necessary to implement such features.
Topics: Animals; Equipment Design; Humans; Microelectrodes; Microtechnology; Neurons
PubMed: 30832357
DOI: 10.3390/s19051069 -
Biosensors Jul 2022The label-free biosensor has emerged as an effective tool for the purpose of early detection of causative pathogens such as as a preventive measure. In this study, a...
The label-free biosensor has emerged as an effective tool for the purpose of early detection of causative pathogens such as as a preventive measure. In this study, a biorecognition-element-free interdigitated microelectrode (IDμE) sensor is designed and developed with this in mind, with good reliability and affordability. Results show that the designed sensor can identify with good selectivity using an impedance and capacitance of 7.69 MHz. At its optimum impedance of 1.3 kHz, the IDμE sensor can reliably quantify in a range of measurement (10~10 cfu/mL), linearity (R = 0.97), sensitivity (18.15 kΩ/log (cfu/mL)), and limit of detection (10 cfu/mL). In summary, the IDμE sensor developed possesses high potential for industrial and clinical applications.
Topics: Biosensing Techniques; Electric Impedance; Escherichia coli O157; Microelectrodes; Reproducibility of Results
PubMed: 35892458
DOI: 10.3390/bios12080561 -
Cells Dec 2021Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes... (Review)
Review
Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.
Topics: Brain; Humans; Microelectrodes; Models, Biological; Neurons; Organoids; Pluripotent Stem Cells
PubMed: 35011667
DOI: 10.3390/cells11010106 -
Acta Biomaterialia Oct 2023Brain-Machine Interface systems (BMIs) are clinically valuable devices that can provide functional restoration for patients with spinal cord injury or improved...
Brain-Machine Interface systems (BMIs) are clinically valuable devices that can provide functional restoration for patients with spinal cord injury or improved integration for patients requiring prostheses. Intracortical microelectrodes can record neuronal action potentials at a resolution necessary for precisely controlling BMIs. However, intracortical microelectrodes have a demonstrated history of progressive decline in the recording performance with time, inhibiting their usefulness. One major contributor to decreased performance is the neuroinflammatory response to the implanted microelectrodes. The neuroinflammatory response can lead to neurodegeneration and the formation of a glial scar at the implant site. Historically, histological imaging of relatively few known cellular and protein markers has characterized the neuroinflammatory response to implanted microelectrode arrays. However, neuroinflammation requires many molecular players to coordinate the response - meaning traditional methods could result in an incomplete understanding. Taking advantage of recent advancements in tools to characterize the relative or absolute DNA/RNA expression levels, a few groups have begun to explore gene expression at the microelectrode-tissue interface. We have utilized a custom panel of ∼813 neuroinflammatory-specific genes developed with NanoString for bulk tissue analysis at the microelectrode-tissue interface. Our previous studies characterized the acute innate immune response to intracortical microelectrodes. Here we investigated the gene expression at the microelectrode-tissue interface in wild-type (WT) mice chronically implanted with nonfunctioning probes. We found 28 differentially expressed genes at chronic time points (4WK, 8WK, and 16WK), many in the complement and extracellular matrix system. Further, the expression levels were relatively stable over time. Genes identified here represent chronic molecular players at the microelectrode implant sites and potential therapeutic targets for the long-term integration of microelectrodes. STATEMENT OF SIGNIFICANCE: Intracortical microelectrodes can record neuronal action potentials at a resolution necessary for the precise control of Brain-Machine Interface systems (BMIs). However, intracortical microelectrodes have a demonstrated history of progressive declines in the recording performance with time, inhibiting their usefulness. One major contributor to the decline in these devices is the neuroinflammatory response against the implanted microelectrodes. Historically, neuroinflammation to implanted microelectrode arrays has been characterized by histological imaging of relatively few known cellular and protein markers. Few studies have begun to develop a more in-depth understanding of the molecular pathways facilitating device-mediated neuroinflammation. Here, we are among the first to identify genetic pathways that could represent targets to improve the host response to intracortical microelectrodes, and ultimately device performance.
Topics: Mice; Animals; Microelectrodes; Electrodes, Implanted; Neuroinflammatory Diseases; Inflammation; Immunity, Innate
PubMed: 37507031
DOI: 10.1016/j.actbio.2023.07.038 -
IEEE Transactions on Bio-medical... Aug 2023Microelectrodes allow the recording of neural activities with a high spatial resolution. However, their small sizes result in high impedance causing high thermal noise...
OBJECTIVE
Microelectrodes allow the recording of neural activities with a high spatial resolution. However, their small sizes result in high impedance causing high thermal noise and poor signal-to-noise ratio. In drug-resistant epilepsy, the accurate detection of Fast Ripples (FRs) can help in the identification of epileptogenic networks. Consequently, good-quality recordings are instrumental in improving surgical outcomes. In this work, we propose a novel model-based approach for the design of microelectrodes optimized for FRs recording.
METHODS
A 3D microscale computational model was developed to simulate FRs generated in the hippocampus. It was coupled with a model of the Electrode-Tissue Interface that accounts for the biophysical properties of intracortical microelectrode. This hybrid model was used to analyze the microelectrode geometrical and physical characteristics and their impact on recorded FRs. For model validation, experimental signals (local field potentials, LFPs) were recorded from CA1 using different electrode materials: stainless steel, gold, and gold coated with poly(3,4-ethylene dioxythiophene)/Poly(styrene sulfonate) (Au:PEDOT/PSS).
RESULTS
results indicated that a radius between 65 and 120 μm for a wire microelectrode is the most optimal for recording FRs. In addition, in silico and in vivo quantified results showed a possible improvement in FRs observability using PEDOT/PSS coated microelectrodes.
CONCLUSION
the optimization of the design of microelectrodes for FRs recording can improve the observability and detectability of FRs which are a recognized marker of epileptogenicity.
SIGNIFICANCE
This model-based approach can assist in the design of hybrid electrodes that can be used in the presurgical evaluation of epileptic patients with drug-resistant epilepsy.
Topics: Humans; Microelectrodes; Polymers; Electrodes, Implanted; Epilepsy; Gold
PubMed: 37028076
DOI: 10.1109/TBME.2023.3250763