Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

Luan, Lan; Wei, Xiaoling; Zhao, Zhengtuo; Siegel, Jennifer J.; Potnis, Ojas; Tuppen, Catherine A; Lin, S.; Kazmi, S. M. Shams; Fowler, Robert; Holloway, Catherine; Dunn, Andrew K.; Chitwood, Raymond A.; Xie, Chong

doi:10.1126/sciadv.1601966

Cited by 489 publications

(584 citation statements)

References 51 publications

Supporting

Mentioning

576

Contrasting

Order By: Relevance

“…In vivo recording was typically performed at 1–2 months after implantation. Taking advantage of the ultraflexibility and the ultrasmall dimensions, we accommodated chronic optical access concurrently with NET‐e implants (Figure 2j) similarly as we recently demonstrated 36…”

Section: Resultsmentioning

confidence: 99%

Nanofabricated Ultraflexible Electrode Arrays for High‐Density Intracortical Recording

et al. 2018

Self Cite

View full text Add to dashboard Cite

Understanding brain functions at the circuit level requires time‐resolved simultaneous measurement of a large number of densely distributed neurons, which remains a great challenge for current neural technologies. In particular, penetrating neural electrodes allow for recording from individual neurons at high temporal resolution, but often have larger dimensions than the biological matrix, which induces significant damage to brain tissues and therefore precludes the high implant density that is necessary for mapping large neuronal populations with full coverage. Here, it is demonstrated that nanofabricated ultraflexible electrode arrays with cross‐sectional areas as small as sub‐10 µm2 can overcome this physical limitation. In a mouse model, it is shown that these electrodes record action potentials with high signal‐to‐noise ratio; their dense arrays allow spatial oversampling; and their multiprobe implantation allows for interprobe spacing at 60 µm without eliciting chronic neuronal degeneration. These results present the possibility of minimizing tissue displacement by implanted ultraflexible electrodes for scalable, high‐density electrophysiological recording that is capable of complete neuronal circuitry mapping over chronic time scales.

show abstract

Section: Resultsmentioning

confidence: 99%

Nanofabricated Ultraflexible Electrode Arrays for High‐Density Intracortical Recording

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent studies have investigated the potential advantages of reducing mechanical stiffness (19)(20)(21), feature sizes (22), as well as density of the material used for fabrication of probes (15) in terms of reduced gliosis. For example, polymer fiber-based neural probes with bending stiffness values ca.…”

mentioning

confidence: 99%

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Zhou

Hong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

193

211

View full text Add to dashboard Cite

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

show abstract

“…The fabrication yield is ~80% with loss mostly due to fabrication defects on the interconnects layer. We choose to use photoresist SU-8 as the insulating layers for its wide range of tunable thickness in spin coating, excellent tensile strength 32 and biocompatibility 33 , the ease of photo-patterning, and extensive prior experience with fabrication using this material 13,14 .…”

Section: Discussionmentioning

confidence: 99%

Nanoelectronic Coating Enabled Versatile Multifunctional Neural Probes

et al. 2017

Self Cite

View full text Add to dashboard Cite

Brain function can be best studied by simultaneous measurements and modulation of the multifaceted signaling at the cellular scale. Extensive efforts have been made to develop multifunctional neural probes, typically involving highly specialized fabrication processes. Here, we report a novel multifunctional neural probe platform realized by applying ultra-thin nanoelectronic coating (NEC) on the surfaces of conventional microscale devices such as optical fibers and micropipettes. We fabricated the NECs by planar photolithography techniques using a substrate-less and multi-layer design, which host arrays of individually addressed electrodes with an overall thickness below 1 μm. Guided by an analytic model and taking advantage of the surface tension, we precisely aligned and coated the NEC devices on the surfaces of these conventional micro-probes, and enabled electrical recording capabilities on par with the state-of-the-art neural electrodes. We further demonstrated optogenetic stimulation and controlled drug infusion with simultaneous, spatially resolved neural recording in a rodent model. This study provides a low-cost, versatile approach to construct multifunctional neural probes that can be applied to both fundamental and translational neuroscience.

show abstract

Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

Abstract: Subcellular-sized, ultraflexible electrodes form seamless integration with the living brain and afford chronically reliable recording.

Cited by 489 publications

References 51 publications

Nanofabricated Ultraflexible Electrode Arrays for High‐Density Intracortical Recording

Nanofabricated Ultraflexible Electrode Arrays for High‐Density Intracortical Recording

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Nanoelectronic Coating Enabled Versatile Multifunctional Neural Probes

Contact Info

Product

Resources

About