Multimodal Neural Probes with Small Form Factor Based on Dual‐Side Fabrication

Abstract

a specific region of the brain through various physical means, including electrical, chemical, optical, and acoustic, have been proposed to investigate neuronal circuits. [8][9][10][11][12] Furthermore, since neurons relay information to downstream neurons through either electrical or chemical synaptic transmission, real-time monitoring of neurotransmitters in the extracellular space of the brain offers additional insight to that observed from the electrophysiological activities. Thus, recently, multimodal neural probes that perform both electrical recording and neurotransmitter detection in the extracellular environment have also been proposed. [13][14][15] However, it is still a challenge to design a multimodal neural probe that detects both neurotransmitters and neural signals at a small form factor. For a multimodal neural probe, while a high-density neural recording and a high electrochemical sensitivity are preferred, a high channel count and sensitivity require a larger shank area. For example, the width of the probe scales linearly with the number of microelectrodes due to the signal lines. Similarly, for electrochemical detection, a larger working electrode (WE) on the shank is also required to achieve high sensitivity. Moreover, to achieve a reliable electrochemical analysis, two electrodes additional to the WE are required to form a three-electrode system. [16] However, because the shank dimension is directly related to the acute neural tissue damage during the insertion, it is important to design a shank with a small dimension. This clear trade-off between the probe dimension (i.e., tissue damage) and performance (i.e., channel counts and high sensitivity) is a major challenge in implementing a multimodal neural probe at a small form factor.To overcome this trade-off, several methods such as multilayer metal interconnect, [17] e-beam photolithography, [18] and dual-sided micropatterning [19,20] have been recently proposed to achieve high density without increasing the dimension of the polymer neural probes. Through these efforts, neural probe arrays with 16-channel SU-8, 32-channel polyimide (PI), and 64-channel Parylene-C (PC) shank have been reported using the standard monolithic microfabrication. [21][22][23][24] In the case of electrochemical analysis, a three-electrode system composed of working, reference, and counter electrodes (WE, RE, and CE) is often used. However, to prevent brain damage from the insertion of the third electrode, a two-electrode system is often Monitoring both individual neuronal spikes and neurotransmitters released from a specific brain region plays a significant role in understanding neuronal circuits and brain functionalities. While polymer neural probe offers distinctive advantages of flexibility, optical transparency, and biocompatibility, achieving high-density recording with multifunctionalities and multimodality is still a challenge due to limited microfabrication techniques. Here, a multimodal polymer neural probe array based on a dual-side fabrication process wit...

Flexible high-density microelectrode arrays for closed-loop brain–machine interfaces: a review

“…Various recent fabricating strategies, including multi-layer strategies ( Pimenta et al, 2021 ) and dual-sided micropatterning ( Tooker et al, 2012 ; Pimenta et al, 2021 ; Kim et al, 2023 ), have been proposed to attain high-density probe capabilities without enlarging the polymer neural probes’ dimensions. Meanwhile, the advances in fabrication techniques also facilitate the development of flexible HDMEAs.…”

“…Scholten et al (2020) introduced a novel polymer-based microelectrode array with an impressive 512 platinum recording electrodes, optimized for chronic recordings in the brains of behaving rats, and showcase advancements in polymer microfabrication and back-side electrode patterning. In the work of Kim et al (2023), a dual-side fabricated multimodal polymer neural probe was developed, featuring gold and platinum 10.3389/fnins.2024.1348434 Frontiers in Neuroscience 10 frontiersin.org microelectrodes. Although a strategy of using multilayer with a sacrificial layer on the bottom could fabricate dual-sided flexible HDMEAs, it introduces challenges, such as misalignment during the multiple lithography processes (Liu et al, n.d.).…”

Miniature Transparent Dopamine Sensor Based on Nanosphere Lithography

“…Along with these advantages, the miniaturization of these sensor systems received widespread interest because of their real‐time monitoring and in vivo measurement capabilities. [ 5 ]…”

“…Along with these advantages, the miniaturization of these sensor systems received widespread interest because of their real-time monitoring and in vivo measurement capabilities. [5] The miniaturization of highly sensitive electrochemical sensors will allow highly compact integration of the sensor into the culture platform. However, because electrochemical sensors are often not transparent, simultaneous chemical detection and optical monitoring in a small in vitro well are difficult.…”

Cellular Calcium Activity at Depth Predicted from Surface Potential Recordings using Ultra-high Density Transparent Graphene Arrays

“…To date, multimodal experiments have been used to investigate the neural dynamics with applications ranging from studies of neural circuits [4][5][6][7][8][9][10] or pathophysiology of brain disorders such as Parkinson's disease [11], Alzheimer's disease [12], and Schizophrenia [13][14][15][16][17] to hybrid brain computer interfaces (BCI) combining two different modalities with complementary strengths to enhance performance [18][19][20][21]. Among these multimodal approaches, experiments concurrently recording electrophysiological during optical imaging and optogenetic stimulation has become a powerful approach to (i) combine temporal resolution advantage of electrophysiology with high spatial resolution and cell-type specificity of optical methods, (ii) to bridge the knowledge gap between basic neuroscience research relying on optical methods employing genetic modifications and clinical research mainly using electrical recordings, and (iii) to expand spatial reach of neural recordings [22] and (iv) to identify cell types through opto-tagging during electrophysiological recordings of neuronal spikes [23,24].…”