Stretchable microelectrode array: Difference between revisions

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{{Multiple issues|

{{essay-like|date=June 2025}}

{{original research|date=June 2025}}

{{refimprove|date=May 2025}}

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{{Short description|Device in neurophysiology}}

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===Material innovation===

* '''Electronic Fillers''': This is the oldest approach to making an [[elastomeric]] material elastically stretchable. In principle, rigid and [[electrically conductive]] materials and mixed with an elastomeric [[polymer]] before curing to create stretchable composites. If the concentration of the electrically conductive filler is high enough they form a mesh-like [[percolation]] network that facilitates the free movement of charge carriers (ions, electrons) through contact junctions. The minimum concentration of the electronic filler material that is required to create conductive pathways for [[charge carrier]] transport through the elastomer<ref>{{cite journal |last1=Kyrylyuk |first1=Andriy V. |last2=van der Schoot |first2=Paul |title=Continuum percolation of carbon nanotubes in polymeric and colloidal media |journal=Proceedings of the National Academy of Sciences |date=17 June 2008 |volume=105 |issue=24 |pages=8221–8226 |doi=10.1073/pnas.0711449105 |doi-access=free |pmid=18550818 |pmc=2448818 |bibcode=2008PNAS..105.8221K }}</ref> is called the [[percolation threshold]].<ref>{{cite book |doi=10.1016/B978-1-895198-95-9.50011-X |chapter=Structure and Distribution of Non-Migrating Antistatics |title=Handbook of Antistatics |date=2016 |pages=117–127 |isbn=978-1-895198-95-9 |editor1-first=Jürgen |editor1-last=Pionteck |editor2-first=George |editor2-last=Wypych }}</ref> The [[percolation threshold]] is usually indicated as weight percentage (wt%) or volume percentage (vol%) of the filler material, and ranges from less than 1wt% for high aspect ration carbon [[nanotubes]] to over 15wt%. The type of filler materials ranges from metals in powder or [[nanowire]] form, [[carbon]] as [[graphite]] or [[nanotubes]], to electrically conducting polymers.

* '''‘Wavy’ [[Nanowires]] and Nanoribbons''': The spontaneous formation of wavy patterns of aligned [[buckles]] that is caused by the deposition of a thin gold film on the surface of the [[elastomer]] [[polydimethylsiloxane]] (PDMS) was first described by the group of George Whitesides at Harvard University in 2000.<ref>{{cite journal |last1=Huck |first1=Wilhelm T. S. |last2=Bowden |first2=Ned |last3=Onck |first3=Patrick |last4=Pardoen |first4=Thomas |last5=Hutchinson |first5=John W. |last6=Whitesides |first6=George M. |title=Ordering of Spontaneously Formed Buckles on Planar Surfaces |journal=Langmuir |date=April 2000 |volume=16 |issue=7 |pages=3497–3501 |doi=10.1021/la991302l }}</ref> The gold was deposited on warmed PDMS (100&nbsp;°C), and, upon cooling and the associated thermal shrinkage of the elastomer, the gold film comes under compressive stress which is relieved by creating [[buckles]]. In subsequent years, the group of John Rogers at the University of Urbana Champaign (now at Northwestern University) has developed the technology to bond very thin silicon ribbons to a pre-stretched PDMS membrane. Upon relaxation of the per-stretch, the compressive [[mechanical stress]] in the [[silicon]] ribbons is relieved by creating wavy buckles in the PDMS. As silicon is a brittle material, the ribbons need to very thin (about 100&nbsp;nm) to stay intact during buckling.<ref>{{cite journal |last1=Kim |first1=Dae-Hyeong |last2=Rogers |first2=John A. |title=Stretchable Electronics: Materials Strategies and Devices |journal=Advanced Materials |date=17 December 2008 |volume=20 |issue=24 |pages=4887–4892 |doi=10.1002/adma.200801788 |bibcode=2008AdM....20.4887K }}</ref>

* '''Liquid Metals''': A [[metal]] or [[alloy]] that is liquid at room temperature can be enclosed in PDMS and used as a stretchable [[Electrical conductor|conductor]]. [[Mercury (element)|Mercury]] is the only pure metal that is liquid at room temperature but has limited application due to its [[neurotoxicity]]. Cesium melts at 28.5&nbsp;°C, but reacts violently when exposed to air and is therefore not suitable for this application. Most researchers therefore use an [[eutectic]] mixture of Indium and Gallium, so called EGaIn, which has a melting point is 15.7&nbsp;°C and consists of 75.5% Gallium and 24.5% Indium. A eutectic mixture of Ga (68.5%), In (21.5%) and Sn (10.0%), also known as [[Galinstan]], is another popular choice and has a melting point of 10.5&nbsp;°C.

* '''Microcracked gold thin film''': When a thin gold film is deposited on PDMS under certain conditions,<ref>{{cite journal |last1=Graudejus |first1=Oliver |last2=Görrn |first2=Patrick |last3=Wagner |first3=Sigurd |title=Controlling the Morphology of Gold Films on Poly(dimethylsiloxane) |journal=ACS Applied Materials & Interfaces |date=28 July 2010 |volume=2 |issue=7 |pages=1927–1933 |doi=10.1021/am1002537 |pmid=20608644 }}</ref> the gold film adopts a microcracked morphology<ref>{{cite journal |last1=Lacour |first1=Stéphanie P. |last2=Chan |first2=Donald |last3=Wagner |first3=Sigurd |last4=Li |first4=Teng |last5=Suo |first5=Zhigang |title=Mechanisms of reversible stretchability of thin metal films on elastomeric substrates |journal=Applied Physics Letters |date=15 May 2006 |volume=88 |issue=20 |doi=10.1063/1.2201874 |bibcode=2006ApPhL..88t4103L |url=http://nrs.harvard.edu/urn-3:HUL.InstRepos:41467478 |url-access=subscription }}</ref> which makes the gold stretchable. The maximum [[Strain (mechanics)|strain]] of the film decreases with the length and increases with the width of the conductor.<ref>{{cite journal |last1=Graudejus |first1=O. |last2=Jia |first2=Zheng |last3=Li |first3=Teng |last4=Wagner |first4=S. |title=Size-dependent rupture strain of elastically stretchable metal conductors |journal=Scripta Materialia |date=June 2012 |volume=66 |issue=11 |pages=919–922 |doi=10.1016/j.scriptamat.2012.02.034 |pmid=22773917 |pmc=3388513 }}</ref>

===Structural design===

* '''Geometric patterning, [[fractal]] patterns''': Metal traces are deposited in specific patterns, such as meandering or [[Serpentine shape|serpentine]] shapes, within a stretchable elastomeric substrate to accommodate [[Strain (mechanics)|strain]]. The resulting structure is akin to a 2-dimensional spring. The University of Ghent and IMEC in Belgium have pioneered the approach to using Meander shaped metallic structures.<ref>{{cite journal |last1=Gonzalez |first1=Mario |last2=Vandevelde |first2=Bart |last3=Christiaens |first3=Wim |last4=Hsu |first4=Yung-Yu |last5=Iker |first5=François |last6=Bossuyt |first6=Frederick |last7=Vanfleteren |first7=Jan |last8=Sluis |first8=Olaf van der |last9=Timmermans |first9=P.H.M. |title=Design and implementation of flexible and stretchable systems |journal=Microelectronics Reliability |date=June 2011 |volume=51 |issue=6 |pages=1069–1076 |doi=10.1016/j.microrel.2011.03.012 |bibcode=2011MiRe...51.1069G }}</ref>

** The group of John Rogers increased the maximum strain in devices created by this approach using fractal-based structures. These fractal patterns are characterized by self-similarity, i.e., a small sections of the structure yields pieces with geometries that resemble the whole structure.

**These fractal patterns include (i) Koch, Peano, Hilbert lines, (ii) Moore, Vicsek loops, and (iii) Greek crosses.<ref>{{cite journal |last1=Fan |first1=Jonathan A. |last2=Yeo |first2=Woon-Hong |last3=Su |first3=Yewang |last4=Hattori |first4=Yoshiaki |last5=Lee |first5=Woosik |last6=Jung |first6=Sung-Young |last7=Zhang |first7=Yihui |last8=Liu |first8=Zhuangjian |last9=Cheng |first9=Huanyu |last10=Falgout |first10=Leo |last11=Bajema |first11=Mike |last12=Coleman |first12=Todd |last13=Gregoire |first13=Dan |last14=Larsen |first14=Ryan J. |last15=Huang |first15=Yonggang |last16=Rogers |first16=John A. |title=Fractal design concepts for stretchable electronics |journal=Nature Communications |date=7 February 2014 |volume=5 |issue=1 |page=3266 |doi=10.1038/ncomms4266 |pmid=24509865 |bibcode=2014NatCo...5.3266F |osti=1875439 }}</ref>

* '''Origami-inspired structures, and [[kirigami]] cuts''': Intrinsically rigid or inelastic flexible materials can be turned into stretchable materials by applying [[origami]] technology<ref>{{cite journal |last1=Chen |first1=Xingru |last2=Li |first2=Yongkai |last3=Wang |first3=Xiaoyi |last4=Yu |first4=Hongyu |title=Origami Paper-Based Stretchable Humidity Sensor for Textile-Attachable Wearable Electronics |journal=ACS Applied Materials & Interfaces |date=10 August 2022 |volume=14 |issue=31 |pages=36227–36237 |doi=10.1021/acsami.2c08245 |pmid=35912486 }}</ref> and kirigami cuts.<ref>{{cite journal |last1=Xu |first1=Renxiao |last2=Zverev |first2=Anton |last3=Hung |first3=Aaron |last4=Shen |first4=Caiwei |last5=Irie |first5=Lauren |last6=Ding |first6=Geoffrey |last7=Whitmeyer |first7=Michael |last8=Ren |first8=Liangjie |last9=Griffin |first9=Brandon |last10=Melcher |first10=Jack |last11=Zheng |first11=Lily |last12=Zang |first12=Xining |last13=Sanghadasa |first13=Mohan |last14=Lin |first14=Liwei |title=Kirigami-inspired, highly stretchable micro-supercapacitor patches fabricated by laser conversion and cutting |journal=Microsystems & Nanoengineering |date=3 December 2018 |volume=4 |issue=1 |page=36 |doi=10.1038/s41378-018-0036-z |pmid=31057924 |pmc=6275159 |bibcode=2018MicNa...4...36X }}</ref>

==History==

The first time the term stretchable multielectrode array (sMEA) [[File:Manually Stretching Microelectrode Array.jpg|thumb|left|Manually stretching sMEA]] Understanding how cells convert [[stimulus (physiology)|mechanical stimuli]] appeared in the literature was in a conference proceeding in 2002 from the Lawrence Livermore National Laboratory.<ref>{{cite book |doi=10.1109/MMB.2002.1002269 |chapter=Stretchable micro-electrode array &#91;for retinal prosthesis&#93; |title=2nd Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.02EX578) |date=2002 |last1=Maghribi |first1=M. |last2=Hamilton |first2=J. |last3=Polla |first3=D. |last4=Rose |first4=K. |last5=Wilson |first5=T. |last6=Krulevitch |first6=P. |pages=80–83 |isbn=0-7803-7480-0 }}</ref> 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.<ref>{{cite book |doi=10.1109/IEMBS.2006.260933 |chapter=Stretchable microelectrode arrays a tool for discovering mechanisms of functional deficits underlying traumatic brain injury and interfacing neurons with neuroprosthetics |title=2006 International Conference of the IEEE Engineering in Medicine and Biology Society |date=2006 |last1=Yu |first1=Zhe |last2=Tsay |first2=Candice |last3=Lacour |first3=Stephanie P. |last4=Wagner |first4=Sigurd |last5=Morrison |first5=Barclay |volume=Suppl |pages=6732–6735 |pmid=17959498 |isbn=1-4244-0032-5 |url=http://infoscience.epfl.ch/record/176599 }}</ref> 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]].<ref>{{cite journal |last1=Meacham |first1=Kathleen W. |last2=Giuly |first2=Richard J. |last3=Guo |first3=Liang |last4=Hochman |first4=Shawn |last5=DeWeerth |first5=Stephen P. |title=A lithographically-patterned, elastic multi-electrode array for surface stimulation of the spinal cord |journal=Biomedical Microdevices |date=April 2008 |volume=10 |issue=2 |pages=259–269 |doi=10.1007/s10544-007-9132-9 |pmid=17914674 |pmc=2573864 }}</ref> 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.<ref>{{cite journal |last1=Yu |first1=Zhe |last2=Graudejus |first2=Oliver |last3=Tsay |first3=Candice |last4=Lacour |first4=Stéphanie P. |last5=Wagner |first5=Sigurd |last6=Morrison |first6=Barclay |title=Monitoring Hippocampus Electrical Activity In Vitro on an Elastically Deformable Microelectrode Array |journal=Journal of Neurotrauma |date=July 2009 |volume=26 |issue=7 |pages=1135–1145 |doi=10.1089/neu.2008.0810 |pmid=19594385 |pmc=2848944 }}</ref>

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.

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====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 (biology)|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 [[Biomechanics|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%).

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 [[Biomechanics|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====

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===In vivo stretchable MEAs===

Stretchable MEAs have many benefits for [[Implant (medicine)|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,<ref>{{cite journal |last1=Graudejus |first1=Oliver |last2=Barton |first2=Cody |last3=Ponce Wong |first3=Ruben D |last4=Rowan |first4=Cami C |last5=Oswalt |first5=Denise |last6=Greger |first6=Bradley |title=A soft and stretchable bilayer electrode array with independent functional layers for the next generation of brain machine interfaces |journal=Journal of Neural Engineering |date=October 2020 |volume=17 |issue=5 |pages=056023 |doi=10.1088/1741-2552/abb4a5 |pmid=33052886 |pmc=7891917 |bibcode=2020JNEng..17e6023G }}</ref> the spinal cord,<ref>{{cite journal |last1=Meacham |first1=Kathleen W. |last2=Giuly |first2=Richard J. |last3=Guo |first3=Liang |last4=Hochman |first4=Shawn |last5=DeWeerth |first5=Stephen P. |title=A lithographically-patterned, elastic multi-electrode array for surface stimulation of the spinal cord |journal=Biomedical Microdevices |date=April 2008 |volume=10 |issue=2 |pages=259–269 |doi=10.1007/s10544-007-9132-9 |pmid=17914674 |pmc=2573864 }}</ref> some involve only stimulation of electrophysiological activity, and some both.<ref>{{cite journal |last1=Rowan |first1=Cami C. |last2=Graudejus |first2=Oliver |last3=Otchy |first3=Timothy M. |title=A Microclip Peripheral Nerve Interface (μcPNI) for Bioelectronic Interfacing with Small Nerves |journal=Advanced Science |date=January 2022 |volume=9 |issue=3 |pages=e2102945 |doi=10.1002/advs.202102945 |pmid=34837353 |pmc=8787429 }}</ref>

====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 (medicine)|implant]] the tissue.<ref name=":0">{{Cite journal |last1=Boufidis |first1=Dimitris |last2=Garg |first2=Raghav |last3=Angelopoulos |first3=Eugenia |last4=Cullen |first4=D. Kacy |last5=Vitale |first5=Flavia |date=2025-02-21 |title=Bio-inspired electronics: Soft, biohybrid, and "living" neural interfaces |journal=Nature Communications |language=en |volume=16 |issue=1 |pages=1861 |doi=10.1038/s41467-025-57016-0 |pmid=39984447 |issn=2041-1723|pmc=11845577 |bibcode=2025NatCo..16.1861B }}</ref>

====Disadvantage====

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==Applications==

===Neural interfaces===

In [[neural interface]]s, 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.<ref name=":0" /> This improves the quality of neural recordings and the effectiveness of neural stimulation, which is crucial for applications such as [[brain-machine interfaces]].<ref name=":0" />

===Electrocorticography===