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, 17 (8), 4588-4595

Nanoelectronic Coating Enabled Versatile Multifunctional Neural Probes

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Nanoelectronic Coating Enabled Versatile Multifunctional Neural Probes

Zhengtuo Zhao et al. Nano Lett.

Abstract

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 ultrathin 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 multilayer 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 microprobes 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.

Keywords: Multifunctional neural probes; controlled drug infusion; optogenetic stimulation; ultrathin nanoelectronic coating.

Conflict of interest statement

Competing financial interests

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1. Schematics of the NEC device enabled multifunctional probe
NEC devices were fabricated separately and attached onto the surface of conventional optical fibers and glass pipettes.
Fig. 2
Fig. 2. Fabrication and characterization of NEC devices enabled multifunctional probes
a – e: photographs of as fabricated NEC devices type a – e on substrate, showing versatile design patterns for broad applications, including linear array of electrodes(a), 2D arrays of 32(b) and 16(c) closely spaced electrodes, 2D arrays of 2×16 electrodes(d) and 4×8 electrodes(e). Scale bar: 100 μm. f: sketch of NEC device cross-section showing the 4-layer substrate-less architect. g: Atomic force microscopy (AFM) measurements across two NEC devices showing the width and thickness. h,i: released NEC device type-a (h) and type-e (i) in water, showing the ultra-flexibility. scale bar: 100 μm. j,k: Sketch illustrating that surface tension facilitates wrapping of a NEC device on the surface of a probe as both are pulled out of water. l: Color-coded dimension dependence of the surface tension and the bending force of the NEC device, marking two regimes: blue, where the surface tension is larger than the bending force so NEC devices readily wraps on the probe surface; pink, where the surface tension is smaller than the bending force so that NEC devices do not fully comply with the probe surface. Critical probe diameters at thickness 0.5 μm and 1 μm are marked by open circles. m – o: photographs of multifunctional probes made of NEC-a wrapped on a glass micropipette (m), NEC-c wrapped on the sidewall (n) and cross-section (o) of optical fibers. scale bar: 100 μm. p,q: scanning electron microscopy (SEM) images of the devices in m and n. scale bar: 100 μm. r,s: zoom-in SEM images in the dashed box in p and q. The arrow highlights the edge of the NEC device and its compliance to the surface of the hosting optical fiber. Scale bar: 50 μm.
Fig. 3
Fig. 3. Demonstration of the NEC device’s electrical recording capacity
a: Photo of a mouse on the treadmill for awake measurement. The mouse was implanted with two multifunctional probes made of NEC-c devices wrapped optical fibers. Inset shows the sketch of the implanted probe. b: 5 s recording traces (300 Hz high-pass filter applied) from the 4 × 8 electrode array (left) of on a multifunctional probe showed in a. Scale bar: 500 μV (vertical) and 0.2s (horizontal). c: Color-coded waveforms from all 20 sorted single-units plotted on the recording electrodes. Waveforms were averaged from all events recorded in 12 mins. Scale bar: 100 μV (vertical) and 1 ms (horizontal). d: Color-coded dots showing the location of neurons inferred from triangulation, where the size of the dots was scaled to the largest peak amplitude in waveforms of the corresponding unit. Same color codes as in c; electrode dimension and separation were drawn to scale. scale bar: 10 μm. e: Numbers of single unit events detected for each unit in 12 minutes recording period. Same color codes as in c and d.
Fig. 4
Fig. 4. Demonstration of simultaneous modulation and recording of the neural activities
a: sketch of a multifunctional probe composed of an optical fiber and NEC-b device. Dashed box marks the electrodes used in b and c. b: Example recording from 4 channels marked in a implanted in a transgenic optogentic mouse (Thy1-mhChR2-EYFP) in mPFC. Shade marks the presence of optical stimulation using a 473 nm continuous laser excitation. Dots indicate the occurrence of APs. Box marks the region shown in c. Histograms of firing rates from individual channels are shown in SFig. 4. Horizontal bar: 2 s. c: 4 channel recording trace of 2 × 3 s (300 Hz high-pass filter applied) selected from 10 × 3 s recording as marked in b. Sorted single-unit waveforms (averaged over 200 spikes) are shown on the right. Scale bar: 50 μV (vertical) and 0.5 ms (horizontal). d: Sketch of a multifunctional probe composed of a glass pipettes and NEC-a device. Dashed box marks the electrodes used in e and f. e: Example recording from 4 channels marked in d implanted in a wild-type mouse in mPFC cortex. Arrows mark the start and finish of the controlled infusion of CNQX at 50 nL/s. Dots mark the occurrence of APs, showing lagged decrease in firing rate with CNQX infusion. Vertical lines mark the region shown in f. Histograms of firing rates in individual channels are shown in SFig. 5. Scale bar: 1 min. f: 4 channel recording trace of 2 × 3 s (300 Hz high-pass filter applied) selected from e as marked. Sorted single-unit waveforms (averaged over 1000 spikes) are shown on the right. Scale bar: 50 μV (vertical) and 0.5 ms (horizontal).

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