A new high-density (25 electrodes/mm2) penetrating microelectrode array for recording and stimulating sub-millimeter neuroanatomical structures

Measurements of electrode impedances and quantified electrode dimensions demonstrated fabrication quality.

“Measurements of the electrode impedances and quantified electrode dimensions demonstrated fabrication quality.”

The authors developed a penetrating electrode array with a 25 electrodes/mm2 density, called the High-Density Utah Slanted Electrode Array (HD-USEA).

“We have recently developed a penetrating electrode array with a 25 electrodes/mm 2 density (called the High-Density Utah Slanted Electrode Array or HD-USEA).”

Physiological and histological evaluations showed no evidence of complete nerve trunk injury after acute (<10 h) implantation of HD-USEAs.

“Physiological and histological evaluations showed no evidence of complete nerve trunk injury [23] after acute (<10 h) implantation of HD-USEAs.”

• cites [23] Lee S K, 2000, J. Am. Acad. Orthop. Surg. sourceNot checked yet

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The average lengths of the longest and shortest electrodes measured from ten HD-USEAs ranged from 884 ± 39 to 310 ± 60 μm.

“The average lengths of the longest and shortest electrodes measured from these ten devices ranged from 884 ± 39 to 310 ± 60 μm, respectively (averages were calculated from all ten electrode rows).”

Selective activation of flexor versus extensor muscles was achieved by delivering stimulation via two catercornered electrodes with an approximate tip-to-tip separation of 208 μm.

“This selective activation of flexor versus extensor muscles was achieved by delivering stimulation via two catercornered electrodes with an approximate tip-to-tip separation of 208 μm.”

In each rat experiment, more than 25 of the 48 wired electrodes were able to record either single-unit or multiunit waveforms.

“In each experiment, there were >25 electrodes out of the 48 wired electrodes that were able to record either single unit or multiunit waveforms.”

In rat preparations, afferent neuronal activity could be recorded via individual HD-USEA electrodes when evoked by tactile and proprioceptive stimuli.

“In the same rat preparations, we were also able to record afferent neuronal activity via individual electrodes that was evoked by tactile and proprioceptive stimuli.”

Electrical stimulation of rat sciatic nerve fibers delivered via individual HD-USEA electrodes could selectively evoke hind limb muscle twitches.

“We observed that electrical stimulation of rat sciatic nerve fibers delivered via individual HD-USEA electrodes could selectively evoke hind limb muscle twitches.”

Delivering voltage-controlled stimulation via individual electrodes on the implanted HD-USEA evoked selective muscle twitches in the ankle flexor and extensor muscles.

“Delivering voltage-controlled stimulation via individual electrodes on the implanted HD-USEA evoked selective muscle twitches in the ankle flexor and extensor muscles.”

The mean signal-to-noise ratio for all three rat preparations across all recording channels was greater than 4.

“The mean SNR for all three preparations across all recording channels was >4.”

The impedances of electrodes de-insulated via plasma etching (n = three arrays) were 440 ± 340 and 179 ± 216 (mean ± sd) kΩ.

“etching (n = three arrays) were 440 ± 340 and 179 ± 216 (mean ± sd) k , respectively.”

The authors successfully fabricated 25 electrodes/mm2 penetrating microelectrode arrays with varying length electrodes designed to access nerve fibers at different depths in small peripheral nerves.

“We have successfully fabricated 25 electrodes/mm 2 penetrating microelectrode arrays with varying length electrodes designed to access nerve fibers that are found at different depths in small peripheral nerves.”

In a feline pudendal nerve implanted with an HD-USEA, there was preservation of the intrafascicular anatomy in the region between electrode tracks.

“As with the sciatic nerve implant, there is preservation of the intrafascicular anatomy in the region between electrode tracks.”

The device de-insulated using the excimer laser technique had a large drop in mean tip impedance to 232 ± 150 kΩ when measured in vivo.

“The device de-insulated using the excimer laser technique had a large drop in mean tip impedance to 232 ± 150 k when measured in vivo.”

Analysis of electrode shank widths at different locations along their lengths across ten electrodes on ten different devices demonstrated uniformity achieved during fabrication.

“Analysis of the widths of the electrode shanks at different locations along their lengths across ten electrodes on ten different devices demonstrates the uniformity that was achieved during fabrication of these devices.”

Mean geometric surface areas for laser de-insulated electrodes were well within the safe limits established for penetrating microelectrodes (GSA 2000 μm2).

“The mean GSAs for the laser de-insulated electrodes were well within the safe limits established for penetrating microelectrodes (GSA 2000 μm 2 ) [29]; however, more work is needed to decrease the GSA of electrodes de-insulated using the foil mask technique.”

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Mean geometric surface areas obtained with laser ablation de-insulation (473 ± 365 μm2) were significantly lower than those from plasma etching (p = 1.06 × 10−26).

“The mean GSAs obtained with the laser ablation de-insulation (473 ± 365 μm 2 ) were significantly lower (alpha = 0.05; p = 1.06 × 10 -26 ; two-tailed student t-test); however, this technique produced much less uniform tip exposures (larger distribution around the mean) likely due to the manual nature of the process.”

• Also stated in: § 5. Conclusions · plain

  “The average GSA of electrode tips de-insulated with the oxygen plasma etching (figure1(b)) and laser ablation (figure1(c)) methods were 4543 ± 526 μm 2 (mean ± sd; n = 17 tips from one device) and 473 ± 365 μm 2 (n = 22 tips from one device), respectively.”

In all three rat preparations, selective contractions of ankle flexor and extensor muscles were evoked by voltage-controlled stimulation via individual HD-USEA electrodes.

“In all three rat preparations, we were able to evoke selective contractions of ankle flexor and extensor muscles, and importantly, such selectivity could be achieved in electrodes with a tip-totip separation as low as 208 μm between electrodes.”

Histological analyses of HD-USEA implant sites showed the nerve axons and fascicles appear to manifest no global damage.

“Importantly, histological analyses of the HD-USEA implant sites showed the nerve axons and fascicles appear to manifest no global damage.”

There was little compression of nerve fibers around the tips and shanks of the HD-USEA electrodes.

“Moreover, there was little compression of the nerve fibers around the tips and shanks of the HD-USEA electrodes, as had been previously noted for the conventionally spaced USEAs [1].”

• Also stated in: § 5. Conclusions · plain

  “Notice there is no axonal compression around the tips (d)-(e) of the electrodes or around the shanks (f) of the electrodes.”

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Cross-sections of acutely implanted rat sciatic nerves (n = 2) and a feline pudendal nerve (n = 1) showed no signs of these types of nerve injuries outside the tracks of the penetrating electrodes.

“The cross-sections of acutely implanted rat sciatic nerves (n = 2) and a feline pudendal nerve (n = 1) showed no signs of these types of nerve injuries outside the tracks of the penetrating electrodes.”

Selective activation of ankle flexor and extensor muscles could be achieved with electrodes having tip-to-tip separation as low as 208 μm.

“In the rat preparation, selective activation of ankle flexor and extensor muscles was achieved by delivering stimulation via two neighboring electrodes in adjacent rows (≈ tip-to-tip separation of 208 μm).”

• Also stated in: § 4.2. In vivo characterization of HD-USEAs · hedged

  “such selectivity could be achieved in electrodes with a tip-totip separation as low as 208 μm between electrodes.”

The shortest HD-USEA electrodes were able to penetrate into fascicles.

“Figure 5 shows that, in fact, the shortest electrodes were able to do so.”

• Also stated in: § 5. Conclusions · plain

  “Microscopic cross section of the nerve shows penetration of a row of shorter length electrodes into the top portion of the rat sciatic nerve fascicles (scale bar = 200 μm).”

Tissue insult from HD-USEA implantation was limited to that produced by the penetrating electrode tips, similar to implantation of arrays four times less dense.

“Tissue insult was limited to that which was produced by the penetrating electrode tips, similar to implantation of arrays that were four times less dense.”

In cat pudendal nerve implanted with HD-USEA, no evidence of complete crush injury or nerve compression was observed.

“Additionally, no evidence of complete crush injury or nerve compression is observed.”

Single or multiunit waveforms were recorded from the 300 μm long electrodes in one animal.

“In addition, we were able to record either single or multiunit waveforms from the 300 μm long electrodes in one animal.”

A microscopic cross section of the rat sciatic nerve shows penetration of shorter HD-USEA microelectrodes (<400 μm in length) with preservation of intrafascicular anatomy between electrode penetration tracks.

“A microscopic cross section of the 1.8 × 0.8 mm nerve shows penetration of the shorter HD-USEA microelectrodes (<400 μm in length) with preservation of the intrafascicular anatomy (epineurial, endoneurial and perineurial) between electrode penetration tracks into the nerve (figure5(c)).”

The three electrode tracks that penetrated into the endoneurium extended approximately 450-500 μm from the edge of the epineurium to the electrode tips.

“The three tracks that penetrate into the endoneurium extend approximately 450-500 μm from the edge of the epineurium to the electrode tips (scale bar = 200 μm).”

In cat pudendal nerve, fibers immediately surrounding the electrode track showed minimal signs of acute damage.

“While substantial loss of fibers in the electrode track is observed, fibers immediately surrounding the track show minimal signs of acute damage.”

In cat pudendal nerve implanted with HD-USEA for <10 h, three of four electrodes penetrated the fascicular space.

“Low-resolution image showing penetration of four electrodes into the nerve, three of which penetrated the fascicular space.”

The results reported herein illustrate that such a delicate architecture can be fabricated consistently.

“The results reported herein illustrate that such a delicate architecture can be fabricated consistently, and importantly, that implantation of such high-density electrode arrays does not cause nerve damage, at least on the acute time frame (<10 h) studied here.”

Selective stimulation of flexor or extensor ankle muscles was achieved by delivering low amplitude (-2 V, steps of increasing pulse-width of 50 μs) stimulation to the 300 μm length electrodes.

“We were also able to selectively stimulate flexor or extensor ankle muscles by delivering low amplitude (-2 V, steps of increasing pulse-width of 50 μs) stimulation to the 300 μm length electrodes.”

In cat pudendal nerve, the electrode penetrated through the epineurium and perineurium into the endoneurial space.

“Close up view of an electrode track from (a) (denoted by arrow) showing penetration of the electrode through the epineurium and perineurium into the endoneurial space (scale bar = 100 μm).”

The desired geometric surface area of the exposed SIROF electrode tips was achieved by oxygen plasma etching and laser ablation techniques.

“The desired GSA of the exposed SIROF electrode tips was achieved by oxygen plasma etching and laser ablation techniques.”

Current peripheral nerve interfaces have electrodes that vary in number of contacts, separated by hundreds of micrometers or several millimeters.

“Current peripheral nerve interfaces have electrodes that vary in their number of contacts, which can be separated by hundreds of micrometers [2,4,5,[11][12][13] or several millimeters [3,7,14].”

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Recent penetrating neural interface applications require a greater number of electrodes (>60) to achieve complex neuromodulation or neurophysiological goals.

“Recent penetrating neural interface applications are requiring a greater number of electrodes (>60) to achieve complex neuromodulation [9,10,16] or neurophysiological [8] goals.”

• cites [9] Simeral J D, 2011, J. Neural Eng. sourceNot checked yet

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• cites [16] Normann R A, 2012, J. Neural Eng. sourceNot checked yet

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Many current peripheral nerve interface devices have a low number of electrodes (<10) implanted interfascicularly, intrafascicularly, or epineurally.

“Many of the devices have a low number of electrodes (<10) that are implanted interfascicularly (e.g.slowly penetrating interfascicular electrode, SPINE [6]), intrafascicularly (e.g.longitudinal intrafascicular electrode, LIFE [15]), or epineurally (e.g.flat interface nerve electrode, FINE [7]).”

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Currently, there is one high electrode-density (6.25 electrodes/mm2), high electrode-count (96 electrodes) penetrating device available for neuromodulation of large structures (>4 mm) in the peripheral nervous system.

“Currently, there is one high electrode-density (6.25 electrodes/mm 2 ), high electrodecount (96 electrodes) penetrating device available for neuromodulation of large structures (> 4 mm) in the peripheral nervous system [1].”

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Some neural interface devices have been fabricated with high electrode densities, but their designs have limited their use to specific central nervous system structures such as cortical grey matter or hippocampal slices.

“Some neural interface devices have been fabricated with high electrode densities; however, their designs have limited the use of these arrays to specific central nervous system structures, such as cortical grey matter (6.25 electrodes/mm 2 [12,13]; >150 electrodes/mm 2 [17,18]) or hippocampal slices (<11 electrodes/mm 2 [19]).”

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• cites [13] Campbell P K, 1990, Biomed. Sci. Instrum.Not checked yet

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Production of a defined geometric surface area (GSA) of the electrode tips was possible using either an oxygen plasma etching technique or excimer laser ablation.

“We have shown that the production of a defined geometric surface area (GSA) of the electrode tips was possible using either an oxygen plasma etching technique [1,21] or by excimer laser ablation [22].”

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• cites [21] Cogan S F Ehrlich J Plante T D Van Wagenen R, 2009, Conf. Proc. IEEE Eng. Med. Biol. Soc.Not checked yet

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As few as 6 electrodes of the conventionally spaced arrays might be functionally implanted into a 1 mm nerve.

“Thus, as few as 6 electrodes of the conventionally spaced arrays might be functionally implanted into a 1 mm nerve.”

Implantation of a 5 × 10 conventional array (0.4 mm electrode spacing with lengths from 0.5 to 1.5 mm) into a 1 mm nerve would result in partial coverage with at most only two electrode rows penetrating into the nerve (20 electrodes).

“For example, implantation of a 5 × 10 conventional array (0.4 mm electrode spacing with lengths from 0.5 to 1.5 mm) into a 1 mm nerve would result in partial coverage with at most only two electrode rows penetrating into the nerve (20 electrodes).”

The nerve remained viable for at least the duration of these experiments (<10 h).

“We were able to record spontaneous and stimulus driven neuronal units on >25 electrodes with an average SNR >4 in all animal preparations, indicating the nerve remained viable for at least the duration of these experiments (<10 h).”

The carbon debris layer is thinner than the parylene-C layer.

“The carbon debris layer is thinner than the parylene-C layer [22], and thus, we hypothesized that the etching of the carbon debris could be carried out in 2 min without the need of a foil mask.”

• cites [22] sourceNot checked yet

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Implantation of such high-density electrode arrays does not cause nerve damage, at least on the acute time frame (<10 h) studied here.

“The results reported herein illustrate that such a delicate architecture can be fabricated consistently, and importantly, that implantation of such high-density electrode arrays does not cause nerve damage, at least on the acute time frame (<10 h) studied here.”

The HD-USEA provides selective access to the fibers of small diameter peripheral nerves.

“Furthermore, the HD-USEA provides selective access to the fibers of small diameter peripheral nerves.”