Stretchable microelectrode array

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Stretchable microelectrode array (sMEA) Stretchable Microelectrode Array (sMEA) with PDMS glue.jpg
Stretchable microelectrode array (sMEA)

Stretchable microelectrode arrays (stretchable MEAs or sMEAs) (also referred to as stretchable multielectrode arrays) are a specialized type of microelectrode array (MEA) with a key advantage; they can be deformed, stretched, bent, and twisted while maintaining electrical functionality whereas standard MEAs break upon mechanical loading. Flexible MEAs (flexMEA), which are often confounded with stretchable MEAs, lie in between stretchable MEAs and standard MEA in terms of their mechanical properties because they bend and twist to some degree, but not stretch. Just like traditional MEAs, stretchable MEAs consist of a few thousand microelectrodes that allow recording or stimulation of electrical signals from cells (neurons, muscles, etc.), and are used in vivo in a living being or in vitro with cell cultures.

Contents

Theory

A stretchable conductor typically consists of two components: an elastomeric insulator and an electrical conductor. There are several approaches to producing stretchable and electrical conducting materials that fall into two categories: structural design and material innovation.

sMEA before and during stretch Stretchable Microelectrode Array (sMEA) before and during stretch.png
sMEA before and during stretch

Material innovation

Structural design

History

The first time the term stretchable multielectrode array (sMEA)

Manually stretching sMEA Manually Stretching Microelectrode Array.jpg
Manually stretching sMEA

Understanding how cells convert mechanical stimuli appeared in the literature was in a conference proceeding in 2002 from the Lawrence Livermore National Laboratory. [12] This paper described the fabrication of an sMEA for a retinal prosthesis, but no biological material was used, i.e., functionality to record or stimulate neural activity was not attempted. The first description of sMEAs being used to record neural activity in biological samples was in 2006 when the research group of Barclay Morrison at Columbia University and Sigurd Wagner at Princeton University reported recording of spontaneous activity in organotypic hippocampal tissue slices. [13] Neither the electrodes nor the tissue appears to have been stretched in these experiments. In 2008, a paper from the Georgia Institute of Technology and Emory University described the use of sMEAs in stimulating a explant of a rat spinal cord. [14] The sMEA was wrapped around the spinal cord, but not stretched, and the cells were electrically stimulated but not used in recording electrophysiological activity. In 2009, another paper of the Morrison/Wagner groups described for the first time the use of an sMEA with a biological sample being stretched as well as electrical stimulation and recording of electrophysiological activity being carried out before and after stretching. [15]

In subsequent years, the number of research papers that describes different approaches to fabricating sMEAs and their use for in vitro and in vivo research has increased immensely.

Types and capabilities

Stretchable microelectrode arrays (sMEAs) can be categorized whether they are used with cells or tissue slices in a dish (in vitro) or whether they are implanted in an animal or human (in vivo).

In vitro stretchable MEAs

sMEAs are used in vitro to record and stimulate electrophysiological activity in dissociated cells, tissue slices or organoids. In vitro use of sMEAs may include stretching of the cells. The cells are either harvested from an animal or were derived from human induced pluripotent stem cells (hiPSCs).

The form factor of sMEAs is often similar to rigid MEAs because the same data acquisition systems can be used for both types of MEAs. The main differences between sMEAs and rigid MEAs are summarized below:

The reason for these differences is that sMEAs are fabricated using soft elastomeric materials such as PDMS as substrate and encapsulation which have a much higher coefficient of thermal expansion and lower Young's Modulus than rigid MEAs that are built on glass, plastic or silicon (CMOS) substrates. These properties make it more challenging to align and bond small features. In addition, the maximum strain that the electrodes can tolerate decreases for narrower electrodes, which is why the electrodes leads are often wide, thus limiting the number electrodes. [16] sMEAs for in vitro applications are only available commercially from BioMedical Sustainable Elastic Electronic Devices. [17]

Advantages

There are several benefits of using soft and stretchable MEAs instead of traditional rigid or merely flexible MEAs. With traditional MEAs, the cells are grown on a rigid substrate material such as glass or plastic. This environment is very different from the natural environment of the cells in the body, which causes the cells to behave differently in vitro than in their natural environment in vivo. This is a major issue for the use of rigid MEAs for pre-clinical research because the goal of pre-clinical research is to predict treatment outcomes in humans. The advantages of using sMEAs for pre-clinical research are twofold. First, the stiffness of the substrate that the cells are grown on matches more closely the stiffness of the cellular environment in the body. Second, sMEAs enable the application of biomechanical cues to the cells, which affect cellular function and behavior. Both of these advantages reduce the mismatch of the environment of cells in vitro and in human body, i.e., the cells behave more similarly in vitro as they do in vivo, which improves the value of pre-clinical research to predict clinical outcomes, thus potentially reducing the failure rate of clinical trials (now >95%).

Disadvantage

The main disadvantage of sMEAs compared to rigid MEAs are related to the different technologies that are used to manufacture these devices. sMEAs have usually up to 60 electrodes with diameters of between 50μm and 100μm where rigid CMOS based MEAs[ citation needed ] can have thousands of electrodes with diameters of 10μm. This means that sMEAs are not suitable for studying sub-cellular structures.

In vivo stretchable MEAs

Stretchable MEAs have many benefits for implantable in vivo applications for recording and stimulation of electrophysiological activity from electrogenic biological tissues (most commonly neurons and muscles). Some applications involve only recording of electrophysiological activity, e.g., on the surface of the brain, [18] the spinal cord, [19] some involve only stimulation of electrophysiological activity, and some both. [20]

Advantages

The main benefits of using sMEAs for in vivo applications are twofold. First, they can conform to the dynamic and often curved surfaces of biological tissues. Second, sMEAs cause significant smaller foreign body reaction than rigid MEAs because of the reduced mismatch in mechanical properties (stiffness) between the implant the tissue.

Disadvantage

The main disadvantage of sMEAs for implanted applications is the mechanical robustness compared to rigid MEAs, which can cause the implant to break or tear.

Applications

Neural interfaces

In neural interfaces, sMEAs are utilized to record and stimulate neural activity. Their stretchability allows them to conform to the brain's surface or penetrate neural tissue without causing significant damage. This improves the quality of neural recordings and the effectiveness of neural stimulation, which is crucial for applications such as brain-machine interfaces.

Electrocorticography

Electrocorticography (EcoG) with stretchable MEAs offers a less invasive method for recording electrical activity from the brain's surface. These arrays can conform to the cortical surface, providing high-resolution, stable recordings even during brain movements. This capability is essential for applications such as epilepsy monitoring and brain-computer interfaces.

Cardiac monitoring

sMEAs are employed in cardiac monitoring and therapy. They can be wrapped around the heart to monitor electrical activity or deliver therapeutic electrical impulses. Their flexibility ensures they remain in contact with the heart's surface despite its constant motion. This application is vital for detecting and treating arrhythmias and other cardiac conditions, providing real-time monitoring and precise intervention.

In vitro research

sMEAs are used in in vitro research to study cellular responses under various mechanical conditions. They enable the monitoring and stimulation of cells in a controlled environment, providing insights into cellular behavior and disease mechanisms. This application is particularly useful in drug testing and the development of new therapies.

Soft robotics

In soft robotics, sMEAs create sensors and actuators that can deform in response to external forces. These applications utilize the mechanical resilience and electrical functionality of sMEAs to develop robots capable of navigating complex environments and performing delicate tasks. Soft robotic systems equipped with sMEAs can adapt to various tasks, from medical procedures to industrial automation.

Conclusion

Stretchable microelectrode arrays represent an advancement in biomedical engineering, with potential applications in neural interfaces, cardiac monitoring, in vitro research, and soft robotics. Research and development efforts continue to focus on overcoming existing challenges to fully realize the potential of these devices.

Related Research Articles

<span class="mw-page-title-main">Electrophysiology</span> Study of the electrical properties of biological cells and tissues.

Electrophysiology is the branch of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and, in particular, action potential activity. Recordings of large-scale electric signals from the nervous system, such as electroencephalography, may also be referred to as electrophysiological recordings. They are useful for electrodiagnosis and monitoring.

A brain–computer interface (BCI), sometimes called a brain–machine interface (BMI), is a direct communication link between the brain's electrical activity and an external device, most commonly a computer or robotic limb. BCIs are often directed at researching, mapping, assisting, augmenting, or repairing human cognitive or sensory-motor functions. They are often conceptualized as a human–machine interface that skips the intermediary of moving body parts (hands...), although they also raise the possibility of erasing the distinction between brain and machine. BCI implementations range from non-invasive and partially invasive to invasive, based on how physically close electrodes are to brain tissue.

Neuroprosthetics is a discipline related to neuroscience and biomedical engineering concerned with developing neural prostheses. They are sometimes contrasted with a brain–computer interface, which connects the brain to a computer rather than a device meant to replace missing biological functionality.

Neural engineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.

In neuroscience, single-unit recordings provide a method of measuring the electro-physiological responses of a single neuron using a microelectrode system. When a neuron generates an action potential, the signal propagates down the neuron as a current which flows in and out of the cell through excitable membrane regions in the soma and axon. A microelectrode is inserted into the brain, where it can record the rate of change in voltage with respect to time. These microelectrodes must be fine-tipped, impedance matching; they are primarily glass micro-pipettes, metal microelectrodes made of platinum, tungsten, iridium or even iridium oxide. Microelectrodes can be carefully placed close to the cell membrane, allowing the ability to record extracellularly.

<span class="mw-page-title-main">Electrocorticography</span> Type of electrophysiological monitoring

Electrocorticography (ECoG), a type of intracranial electroencephalography (iEEG), is a type of electrophysiological monitoring that uses electrodes placed directly on the exposed surface of the brain to record electrical activity from the cerebral cortex. In contrast, conventional electroencephalography (EEG) electrodes monitor this activity from outside the skull. ECoG may be performed either in the operating room during surgery or outside of surgery. Because a craniotomy is required to implant the electrode grid, ECoG is an invasive procedure.

Local field potentials (LFP) are transient electrical signals generated in nerves and other tissues by the summed and synchronous electrical activity of the individual cells in that tissue. LFP are "extracellular" signals, meaning that they are generated by transient imbalances in ion concentrations in the spaces outside the cells, that result from cellular electrical activity. LFP are 'local' because they are recorded by an electrode placed nearby the generating cells. As a result of the Inverse-square law, such electrodes can only 'see' potentials in a spatially limited radius. They are 'potentials' because they are generated by the voltage that results from charge separation in the extracellular space. They are 'field' because those extracellular charge separations essentially create a local electric field. LFP are typically recorded with a high-impedance microelectrode placed in the midst of the population of cells generating it. They can be recorded, for example, via a microelectrode placed in the brain of a human or animal subject, or in an in vitro brain thin slice.

A hybrot is a cybernetic organism in the form of a robot controlled by a computer consisting of both electronic and biological elements. The biological elements are typically rat neurons connected to a computer chip.

A cultured neuronal network is a cell culture of neurons that is used as a model to study the central nervous system, especially the brain. Often, cultured neuronal networks are connected to an input/output device such as a multi-electrode array (MEA), thus allowing two-way communication between the researcher and the network. This model has proved to be an invaluable tool to scientists studying the underlying principles behind neuronal learning, memory, plasticity, connectivity, and information processing.

A microelectrode is an electrode used in electrophysiology either for recording neural signals or for the electrical stimulation of nervous tissue. Pulled glass pipettes with tip diameters of 0.5 μm or less are usually filled with 3 molars potassium chloride solution as the electrical conductor. When the tip penetrates a cell membrane the lipids in the membrane seal onto the glass, providing an excellent electrical connection between the tip and the interior of the cell, which is apparent because the microelectrode becomes electrically negative compared to the extracellular solution. There are also microelectrodes made with insulated metal wires, made from inert metals with high Young modulus such as tungsten, stainless steel, or platinum-iridium alloy and coated with glass or polymer insulator with exposed conductive tips. These are mostly used for recording from the external side of the cell membrane. More recent advances in lithography have produced silicon-based microelectrodes.

<span class="mw-page-title-main">Stretchable electronics</span>

Stretchable electronics, also known as elastic electronics or elastic circuits, is a group of technologies for building electronic circuits by depositing or embedding electronic devices and circuits onto stretchable substrates such as silicones or polyurethanes, to make a completed circuit that can experience large strains without failure. In the simplest case, stretchable electronics can be made by using the same components used for rigid printed circuit boards, with the rigid substrate cut to enable in-plane stretchability. However, many researchers have also sought intrinsically stretchable conductors, such as liquid metals.

Microelectrode arrays (MEAs) are devices that contain multiple microelectrodes through which neural signals are obtained or delivered, essentially serving as neural interfaces that connect neurons to electronic circuitry. There are two general classes of MEAs: implantable MEAs, used in vivo, and non-implantable MEAs, used in vitro. In each class, there are rigid, flexible, and stretchable microelectrode array.

Neurostimulation is the purposeful modulation of the nervous system's activity using invasive or non-invasive means. Neurostimulation usually refers to the electromagnetic approaches to neuromodulation.

An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture, integrated circuit (chip) that simulates the activities, mechanics and physiological response of an entire organ or an organ system. It constitutes the subject matter of significant biomedical engineering research, more precisely in bio-MEMS. The convergence of labs-on-chips (LOCs) and cell biology has permitted the study of human physiology in an organ-specific context. By acting as a more sophisticated in vitro approximation of complex tissues than standard cell culture, they provide the potential as an alternative to animal models for drug development and toxin testing.

<span class="mw-page-title-main">Platinum–iridium alloy</span> Alloys of the precious metals platinum and iridium

Platinum–iridium alloys are alloys of the platinum group precious metals platinum and iridium.

<span class="mw-page-title-main">Surface chemistry of neural implants</span>

As with any material implanted in the body, it is important to minimize or eliminate foreign body response and maximize effectual integration. Neural implants have the potential to increase the quality of life for patients with such disabilities as Alzheimer's, Parkinson's, epilepsy, depression, and migraines. With the complexity of interfaces between a neural implant and brain tissue, adverse reactions such as fibrous tissue encapsulation that hinder the functionality, occur. Surface modifications to these implants can help improve the tissue-implant interface, increasing the lifetime and effectiveness of the implant.

A chronic electrode implant is an electronic device implanted chronically into the brain or other electrically excitable tissue. It may record electrical impulses in the brain or may stimulate neurons with electrical impulses from an external source.

A cortical implant is a subset of neuroprosthetics that is in direct connection with the cerebral cortex of the brain. By directly interfacing with different regions of the cortex, the cortical implant can provide stimulation to an immediate area and provide different benefits, depending on its design and placement. A typical cortical implant is an implantable microelectrode array, which is a small device through which a neural signal can be received or transmitted.

<span class="mw-page-title-main">Stéphanie P. Lacour</span> French neurotechnologist

Stéphanie P. Lacour is a French neurotechnologist and full professor holding the Foundation Bertarelli Chair in Neuroprosthetic Technology at the Swiss Federal Institute of Technology in Lausanne (EPFL). Lacour is a pioneer in the field of stretchable electronics and directs a laboratory at EPFL which specializes in the development of Soft BioElectronic Interfaces to enable seamless integration of neuroprosthetic devices into human tissues. Lacour is also a co-founding member and director of the Center for Neuroprosthetics at the EPFL Satellite Campus in Geneva, Switzerland.

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