Neural Circuits on a Chip (original) (raw)
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Biosensors & bioelectronics, 2006
In vitro culture of small neuronal networks with pre-defined topological features is particularly desirable when the electrical activity of such assemblies can be monitored for long periods of time. Indeed, it is hoped that such networks, with pre-determined connectivity, will provide unique insights into the structure/function relationship of biological neural networks and their properties of self-organization. However, the experimental techniques that have been developed so far for that purpose have either failed to provide very long-term pattern definition and retention, or they have not shown potential for integration into more complex microfluidic devices. To address this problem, three-dimensional microfluidic systems in poly(dimethylsiloxane) (PDMS) were fabricated and used in conjunction with both custom-made and commercially available planar microelectrode arrays (pMEAs). Various types of primary neuronal cell cultures were established inside these systems. Extracellular electrical signals were successfully recorded from all types of cells placed inside the patterns, and this bioelectrical activity was present for several weeks. The advantage of this approach is that it can be further integrated with microfluidic devices and pMEAs to yield, for example, complex neuron-based biosensors or chips for pharmacological screening.
Lab-on-Chip Microsystems for Ex Vivo Network of Neurons Studies: A Review
Frontiers in Bioengineering and Biotechnology, 2022
Increasing population is suffering from neurological disorders nowadays, with no effective therapy available to treat them. Explicit knowledge of network of neurons (NoN) in the human brain is key to understanding the pathology of neurological diseases. Research in NoN developed slower than expected due to the complexity of the human brain and the ethical considerations for in vivo studies. However, advances in nanomaterials and micro-/nano-microfabrication have opened up the chances for a deeper understanding of NoN ex vivo, one step closer to in vivo studies. This review therefore summarizes the latest advances in lab-on-chip microsystems for ex vivo NoN studies by focusing on the advanced materials, techniques, and models for ex vivo NoN studies. The essential methods for constructing lab-on-chip models are microfluidics and microelectrode arrays. Through combination with functional biomaterials and biocompatible materials, the microfluidics and microelectrode arrays enable the d...
Joining microelectronics and microionics: Nerve cells and brain tissue on semiconductor chips
Solid-State Electronics, 2008
The direct electrical interfacing of semiconductor chips with individual nerve cells and with brain tissue is considered. At first, the structure of the cell-chip contact is described and then the electrical coupling is characterized between ion channels, the electrical elements of nerve cells, and transistors and capacitors of silicon chips. On that basis, the signal transmission between microelectronics and microionics is implemented in both directions. Simple hybrid systems are assembled with neuron pairs and with small neuronal networks. Finally, the interfacing with capacitors and transistors is extended to brain tissue on silicon. The application of CMOS chips with capacitively coupled recording sites allows an imaging of neuronal activity with high spatiotemporal resolution. Goal of the work is an integration of neuronal network dynamics and digital electronics on a microscopic level for applications in brain research, medical prosthetics and information technology.
Modular microstructure design to build neuronal networks of defined functional connectivity
Biosensors and Bioelectronics, 2018
Theoretical and in vivo neuroscience research suggests that functional information transfer within neuronal networks is inuenced by circuit architecture. Due to the dynamic complexities of the brain, it remains a challenge to test the correlation between structure and function of a dened network. Engineering controlled neuronal networks in vitro oers a way to test structural motifs; however, no method has achieved small, multi-node networks with stable, unidirectional connections. Here, we screened ten dierent microchannel architectures within polydimethylsiloxane (PDMS) devices to test their potential for axonal guidance. The most successful design had a probability of 92% of achieving strictly unidirectional connections between nodes. Networks built from this design were cultured on multielectrode arrays and recorded on days in vitro 9, 12, 15 and 18 to investigate spontaneous and evoked bursting activity. Transfer entropy between subsequent nodes showed up to 100 times more directional ow of information compared to the control. Additionally, directed networks produced a greater amount of information ow, reinforcing the importance of directional connections in the brain being critical for reliable communication. By controlling the parameters of network formation, we minimized response variability and achieved functional, directional networks. The technique provides us with a tool to probe the spatio-temporal eects of dierent network motifs.
On the Way to Large-Scale and High-Resolution Brain-Chip Interfacing
Cognitive Computation, 2012
Brain-chip-interfaces (BCHIs) are hybrid entities where chips and nerve cells establish a close physical interaction allowing the transfer of information in one or both directions. Typical examples are represented by multi-site-recording chips interfaced to cultured neurons, cultured / acute brain slices, or implanted "in vivo". This paper provides an overview on recent achievements in our laboratory in the field of BCHIs leading to enhancement of signals transmission from nerve cells to chip or from chip to nerve cells with an emphasis on in-vivo interfacing, either in terms of signal-tonoise ratio or of spatiotemporal resolution. Oxide-insulated chips featuring large-scale and highresolution arrays of stimulation and recording elements are presented as a promising technology for high spatiotemporal resolution interfacing, as recently demonstrated by recordings obtained from hippocampal slices and brain cortex in implanted animals. Finally, we report on an automated tool for processing and analysis of acquired signals by BCHIs.
Microenvironments Matter: Advances in Brain-on-Chip
Biosensors
To highlight the particular needs with respect to modeling the unique and complex organization of the human brain structure, we reviewed the state-of-the-art in devising brain models with engineered instructive microenvironments. To acquire a better perspective on the brain’s working mechanisms, we first summarize the importance of regional stiffness gradients in brain tissue, varying per layer and the cellular diversities of the layers. Through this, one can acquire an understanding of the essential parameters in emulating the brain in vitro. In addition to the brain’s organizational architecture, we addressed also how the mechanical properties have an impact on neuronal cell responses. In this respect, advanced in vitro platforms emerged and profoundly changed the methods of brain modeling efforts from the past, mainly focusing on animal or cell line research. The main challenges in imitating features of the brain in a dish are with regard to composition and functionality. In neur...
Translational challenges associated with reduction-ist modeling approaches, as well as ethical concerns and economic implications of small animal testing, drive the need for developing microphysiological neural systems for modeling human neurological diseases, disorders, and injuries. Here, we provide a comprehensive review of microphysiological brain and neural systems-on-a-chip (NSCs) for modeling higher order trajectories in the human nervous system. Societal, economic , and national security impacts of neurological diseases, disorders, and injuries are highlighted to identify critical NSC application spaces. Hierarchical design and manufacturing of NSCs are discussed with distinction for surface-and bulk-based systems. Three broad NSC classes are identified and reviewed: microfluidic NSCs, compartmentalized NSCs, and hydrogel NSCs. Emerging areas and future directions are highlighted, including the application of 3D printing to design and manufacturing of next-generation NSCs, the use of stem cells for constructing patient-specific NSCs, and the application of human NSCs to 'personalized neurology'. Technical hurdles and remaining challenges are discussed. This review identifies the state-of-the-art design methodologies, manufacturing approaches, and performance capabilities of NSCs. This work suggests NSCs appear poised to revolutionize the modeling of human neurological diseases, disorders, and injuries. Keywords Organ-on-a-chip. Brain-on-a-chip. Nervous system-on-a-chip. Microfluidics. 3D bioprinting. 3D cell culture
Building an organic computing device with multiple interconnected brains.
Recently, we proposed that Brainets, i.e. networks formed by multiple animal brains, cooperating and exchanging information in real time through direct brain-to-brain interfaces, could provide the core of a new type of computing device: an organic computer. Here, we describe the first experimental demonstration of such a Brainet, built by interconnecting four adult rat brains. Brainets worked by concurrently recording the extracellular electrical activity generated by populations of cortical neurons distributed across multiple rats chronically implanted with multi-electrode arrays. Cortical neuronal activity was recorded and analyzed in real time, and then delivered to the somatosensory cortices of other animals that participated in the Brainet using intracortical microstimulation (ICMS). Using this approach, different Brainet architectures solved a number of useful computational problems, such as discrete classification, image processing, storage and retrieval of tactile information, and even weather forecasting. Brainets consistently performed at the same or higher levels than single rats in these tasks. Based on these findings, we propose that Brainets could be used to investigate animal social behaviors as well as a test bed for exploring the properties and potential applications of organic computers.
2013 6th International IEEE/EMBS Conference on Neural Engineering (NER), 2013
Despite the extensive use of in-vitro models for neuroscientific investigations and notwithstanding the growing field of network electrophysiology, all studies on cultured cells devoted to elucidate neurophysiological mechanisms and computational properties, are based on 2D neuronal networks. These networks are usually grown onto specific rigid substrates (also with embedded electrodes) and lack of most of the constituents of the in-vivo like environment: cell morphology, cell-to-cell interaction and neuritic outgrowth in all directions. Cells in a brain region develop in a 3D space and interact with a complex multi-cellular environment and extracellular matrix. Under this perspective, 3D networks coupled to micro-transducer arrays, represent a new and powerful in-vitro model capable of better emulating in-vivo physiology. In this work, we present a new experimental paradigm constituted by 3D hippocampal networks coupled to Micro-Electrode-Arrays (MEAs) and we show how the features of the recorded network dynamics differ from the corresponding 2D network model. Further development of the proposed 3D in-vitro model by adding embedded functionalized scaffolds might open new prospects for manipulating, stimulating and recording the neuronal activity to elucidate neurophysiological mechanisms and to design bio-hybrid microsystems. S everal studies have been devoted to the introduction of in-vitro 3D neuronal systems but the use of such experimental models is still limited and, as far as we know, no attempt of functional multisite electrophysiological measurements of 3D neuronal networks has been presented in the literature. The potential advantages of 3D engineered constructs are evident as they can be used as a more accurate investigational in-vitro platform or as the basis for developing living bio-hybrid neuro-electronic microsystems in-vitro or in-vivo 1 . Thus the design and implementation of 3D engineered neuronal networks with embedded sensors and recordingstimulating electrodes, would give new opportunities for investigations and applications in the neuroscientific domain. On the other hand, the development of such 3D network architectures and the possibility of chronic and functional electrophysiological recordings pose new challenges in terms of integration between scaffolds and recording-stimulating devices, long-term cell survival, exchange of nutrients, cell coupling with micro-electrodes and micro-sensors, etc. Till now, most of the efforts have been devoted to the development of new materials 2 , passive 3,4 and active scaffolds 5 , and new experimental procedures to guarantee the development of 3D cultured networks; however, multi-site electrophysiological recordings in such 3D neuronal preparations are still lacking.
Neuron-Semiconductor Chip with Chemical Synapse between Identified Neurons
Physical Review Letters, 2004
Noninvasive electrical stimulation and recording of neuronal networks from semiconductor chips is a prerequisite for the development of neuroelectronic devices. In a proof-of-principle experiment, we implemented the fundamental element of such future hybrids by joining a silicon chip with an excitatory chemical synapse between a pair of identified neurons from the pond snail. We stimulated the presynaptic cell (VD4) with a chip capacitor and recorded the activity of the postsynaptic cell (LPeD1) with a transistor. We enhanced the strength of the soma-soma synapse by repetitive capacitor stimulation, establishing a neuronal memory on the silicon chip.