Draft:Stretchable Microelectrode Array (sMEAs)

Overview

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Stretchable microelectrode arrays (sMEAs)

 
Stretchable Microelectrode Array (sMEA)

are cutting-edge devices that merge the mechanical properties of flexible substrates with the functional capabilities of traditional microelectrode array. These arrays are particularly beneficial for electrophysiological applications, enabling both the recording and stimulation of electrical activity in cells and tissues.[1] Their ability to endure mechanical strains such as stretching, bending, and twisting makes them ideal for applications requiring durability and conformability.

Technology and Properties

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sMEAs utilize microcracked gold films on polydimethylsiloxane (PDMS) substrates.[2] These films offer several key advantages:

 
sMEA before and during stretch
  • Elastic Stretchability: Allows the electrodes to stretch with the tissue without losing conductivity, maintaining functionality even when stretched over 70%.[3]
  • Mechanical Robustness: Can endure repeated cycles of stretching, bending, and twisting.[4]

Microcracked gold films are central to sMEA functionality. These films consist of micro-scale cracks that enable the gold layer to stretch elastically without losing conductivity.[5] This property contrasts sharply with smooth gold films, which rupture at strains below 2%, ceasing to conduct electricity. Controlling the morphology of these films is crucial and involves adjusting parameters such as the elastic modulus, pre-treatment of the silicone, film thickness, deposition temperature, and adhesion layer.

How Stretchable Microelectrode Arrays (sMEAs) Work

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Integrated cell stretching, imaging, and electrophysiology device

sMEAs can be integrated into a cell stretching tool or cyctostretcher, which combines electrophysiology, mechanical stretching, and imaging into a single platform. This system allows researchers to manipulate chemical, electrical, and mechanical environments independently, closely replicating the complex conditions found in vivo. This integration is vital for studying various physiological and pathological processes in a controlled setting.

Cell stretching tools reproduce the electrical and mechanical environment of cells in the body, providing more accurate and relevant data. By using sMEAs, researchers can concurrently apply multiple experimental paradigms, saving time, money, and reducing the use of research animals.

Advantages

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The primary advantages of using sMEAs include the ability to:

  • Simulate the natural mechanical environment of cells, leading to more physiologically relevant data. This simulation is crucial for understanding how cells and tissues respond to mechanical stress in the body, providing insights into various physiological and pathological processes.
  • Reduce the need for animal testing by providing more accurate in vitro models. By closely mimicking the in vivo environment, sMEAs allow for more reliable and ethical research methods, reducing the reliance on animal models in preclinical studies.
  • Enhance the efficiency and reliability of drug screening processes, potentially lowering the failure rate of clinical trials.[6] By providing a platform for early identification of promising drug candidates, sMEAs help streamline the drug development process, saving time and resources.

These sMEAs are designed to be soft, flexible, and elastically stretchable substrates for cells to grow on[7], ensuring compatibility with various data acquisition systems, such as BMSEED's electrophysiology module, and enhancing the efficiency and reliability of electrophysiological recordings.

 
Data acquisition system

Standard sMEAs feature up to 56 microelectrodes and 4 internal reference electrodes for high-density recordings, or users can customize the electrode number and layout for a given research application or cell type.

Applications

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Stretchable microelectrode arrays (sMEAs) are a new and emerging technology with a wide range of potential applications.

In Vitro Research

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Providing a more accurate model for studying cell behavior by replicating the mechanical and electrical environment of living tissues.

The ability of sMEAs to replicate in vivo conditions more accurately makes them invaluable for in vitro research.[8] They provide a platform for studying cell behavior under mechanical and electrical conditions that closely mimic those in the human body, improving the predictive power of in vitro models for in vivo behavior.

Neuroprotective Drug Screening

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Offering a platform to test drugs' effects on neuronal health and function, particularly useful in conditions like Alzheimer's disease and traumatic brain injury.[9][10]

sMEAs are used to screen drugs for their neuroprotective effects, particularly in the context of neurotraumatic injuries and neurodegenerative diseases such as Alzheimer’s. By providing a reliable platform for assessing neuronal health and function, sMEAs help identify promising drug candidates early in the research process.

Mechanotransduction Studies

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Manually stretching sMEA

Understanding how cells convert mechanical stimuli into electrical or chemical signals,[11] which is vital for insights into various cellular processes.

The study of mechanotransduction, the process by which cells convert mechanical stimuli into electrical or chemical signals, benefits greatly from the use of sMEAs. These arrays allow researchers to apply controlled mechanical strains to cells and tissues while simultaneously recording the resulting electrophysiological responses, providing insights into fundamental cellular processes.

The applications of sMEAs are still being explored, they have the potential to revolutionize a wide range of fields.

References

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  1. ^ Lacour, S.P., Benmerah, S., Tarte, E. et al. Flexible and stretchable micro-electrodes for in vitro and in vivo neural interfaces. Med Biol Eng Comput 48, 945–954 (2010). https://doi.org/10.1007/s11517-010-0644-8
  2. ^ Oliver Graudejus, Patrick Görrn, and Sigurd Wagner. Controlling the Morphology of Gold Films on Poly(dimethylsiloxane. ACS Applied Materials & Interfaces 2 (7), 1927-1933 (2010). https://doi.org/10.1021/am1002537
  3. ^ O. Graudejus, Z. Yu, J. Jones, B. Morrison III, S. Wagner (2009) Characterization of an elastically stretchable microelectrode array and its application to neural field potential recordings, Journal of the Electrochemical Society, 156(6):P85-P94.
  4. ^ Ingrid M. Graz,a Darryl P. J. Cotton, Stephanie P. Lacour (2009) Extended cyclic uniaxial loading of stretchable gold thin-films on elastomeric substrates. Applied Physics Letters 94:071902.
  5. ^ Stéphanie P. Lacour, Donald Chan, Sigurd Wagner, Teng Li, Zhigang Suo (2006) Mechanisms of reversible stretchability of thin metal films on elastomeric substrates. Applied Physics Letters 88:204103.
  6. ^ Kabadi SV, Faden AI. Neuroprotective strategies for traumatic brain injury: improving clinical translation. Int J Mol Sci. 2014 Jan 17;15(1):1216-36. doi: 10.3390/ijms15011216. PMID: 24445258; PMCID: PMC3907865.
  7. ^ Nic D. Leipzig, Molly S. Shoichet (2009) The effect of substrate stiffness on adult neural stem cell behavior. Biomaterials 30(36):6867-6878
  8. ^ Yu Z, Graudejus O, Tsay C, Lacour SP, Wagner S, Morrison B 3rd. Monitoring hippocampus electrical activity in vitro on an elastically deformable microelectrode array. J Neurotrauma. 2009 Jul;26(7):1135-45. doi: 10.1089/neu.2008.0810. PMID: 19594385; PMCID: PMC2848944.
  9. ^ Woo Hyeun Kang, Wenzhe Cao, Oliver Graudejus, Tapan P. Patel, Sigurd Wagner, David F. Meaney, and Barclay MorrisonIII. Alterations in Hippocampal Network Activity after In Vitro Traumatic Brain Injury. Journal of Neurotrauma 2015 32:13, 1011-1019
  10. ^ Dwyer MKR, Amelinez-Robles N, Polsfuss I, Herbert K, Kim C, Varghese N, Parry TJ, Buller B, Verdoorn TA, Billing CB Jr, Morrison B 3rd. NTS-105 decreased cell death and preserved long-term potentiation in an in vitro model of moderate traumatic brain injury. Exp Neurol. 2024 Jan;371:114608. doi: 10.1016/j.expneurol.2023.114608. Epub 2023 Nov 9. PMID: 37949202.
  11. ^ Kefauver JM, Ward AB, Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels. Nature. 2020 Nov;587(7835):567-576. doi: 10.1038/s41586-020-2933-1. Epub 2020 Nov 25. PMID: 33239794; PMCID: PMC8477435.