Brain-computer interfaces (BCIs) are miniaturized tools crucial for recording neural signals with high resolution, offering insights into neural circuitry and potential applications in treating neurological disorders and developing neuroprosthetics. Existing BCI devices, like Utah electrodes and Michigan probes, while sophisticated, often utilize rigid materials (metal or silicon) with a higher elastic modulus than brain tissue. This mismatch causes significant stress, leading to acute neuron damage, disruption of blood vessels during implantation, and chronic immune responses. Glial scar formation further increases contact resistance and deteriorates signal quality. To address these limitations, flexible BCI devices made from polymers have emerged, offering better compliance with biological tissue, reduced shear motion, and suppressed neuroinflammatory responses. Previous research has explored minimally-invasive flexible probes with smaller cross-sections and flexible polyimide neural threads for improved implantation. While ultrasmall cross-section devices fabricated using SU-8 offer reduced footprints, their cost and biocompatibility remain concerns. Polyimide (PI), known for its chemical stability and thermal resistance, especially photosensitive PI suitable for photolithography, has shown promise in biomedical applications. This paper presents a MEMS-fabricated flexible neural implant with an ultrathin PI substrate for low-invasive implantation. The device's high aspect ratio and small cross-section minimize trauma and inflammatory responses. Electrodes modified with Pt-black are designed for local field potential (LFP) and spike recording, and a rigid silicon shuttle ensures implantation accuracy.

The development of Brain Computer Interfaces (BCIs) has been driven by the need for high-resolution neural signal recording and the potential for treating neurological diseases and enhancing brain-computer communication. Traditional rigid implants, while effective in recording neural activity, often cause significant trauma and immune response due to the mismatch in mechanical properties between the implant and the surrounding brain tissue. This has led researchers to explore flexible and minimally invasive alternatives. Studies have demonstrated that flexible polymer-based implants, with their reduced stiffness and better biocompatibility, significantly improve long-term performance and reduce inflammation compared to rigid metallic implants. Specific examples include the minimally-invasive flexible intracortical probe by Srikantharajah et al., featuring a small cross-section for improved immune acceptance. Musk et al. introduced flexible polyimide neural threads for efficient robotic implantation. Other research has focused on reducing the cross-sectional area of the implant further to subcellular dimensions using SU-8, although concerns about its biocompatibility persist. Polyimide (PI), a widely used polymer in biomedical applications, offers a viable alternative due to its excellent chemical stability, thermal resistance, and biocompatibility. The use of photosensitive PI allows for complex device structures through photolithography, leading to various PI-based implant designs.

The researchers designed and fabricated a MEMS-based flexible neural implant with an ultrathin polyimide (PI) substrate. The device consists of eight electrodes (four macroelectrodes for LFP recording and four microelectrodes for spike recording) evenly distributed on the PI substrate, all modified with Pt-black to improve charge storage and reduce impedance. The bending stiffness of the device was calculated using the formula K = EI/b³h³/12, where E is Young's modulus, I is rotary inertia, b is width, and h is thickness. To minimize the bending stiffness, an ultrathin PI film (5 µm and even down to 500 nm by mixing with MNP) was created using spin coating. For accurate implantation, a rigid silicon shuttle with an optimized structure and surface micro-grooves was designed. Polyethylene glycol (PEG) served as a temporary adhesive to bind the flexible substrate to the shuttle during implantation. The fabrication process involved separate MEMS fabrication of the flexible substrate and silicon shuttle. The substrate was created by sequential patterning of the bottom PI layer, Cr/Au layer (conductive layer), top PI layer, and electrode metal layer, followed by release in hydrochloric acid. The silicon shuttle was fabricated using photolithography and deep reactive ion etching. Pt coating was electroplated onto the electrodes. The assembly involved oxygen plasma cleaning of the shuttle, applying melted PEG to the shuttle shank, transferring the flexible substrate, and adding a PEG pellet to strengthen the bond. The device was then glued to a 3D-printed board, and a flexible printed circuit (FPC) was connected using an anisotropic conductive film. Mechanical testing involved tensile tests using a thermomechanical analyzer to determine Young's modulus and fracture force. Finite element analysis (FEA) using ABAQUS software simulated the bending behavior of the device at different thicknesses and bending diameters to determine the maximum van Mises stress. The thickness scalability of the PI substrate was investigated by varying the ratio of PI precursor to MNP.

The study successfully demonstrated the fabrication and in vivo testing of a flexible neural implant with an ultrathin PI substrate. Mechanical testing showed that the 5 µm thick PI substrate had a Young's modulus of 3.14 GPa and could withstand significant tensile forces. FEA analysis showed that the thinner substrate (5 µm) exhibited better flexibility with lower stress under bending compared to thicker substrates. The researchers successfully created a PI substrate thickness as low as 500nm by adding MNP to the PI precursor, which is measured by the profilometer for the whole device (1µm thick). This thin flexible substrate is able to wrap around a 0.8 mm needle tip, demonstrating its high flexibility. The incorporation of Pt-black electrode modification enhanced charge storage and reduced impedance. In vivo experiments in mice showed successful implantation with minimal trauma, and neuronal signals were recorded for one month post-implantation, indicating the long-term stability and biocompatibility of the device. The bending stiffness of the 1 µm-thick device was calculated to be 2.6 × 10⁻¹⁴ N·m², comparable to that of axons.

The results demonstrate the feasibility of creating a low-invasive flexible neural implant with significantly improved mechanical properties compared to traditional rigid implants. The ultrathin PI substrate, combined with the optimized design of the silicon shuttle and Pt-black electrode modification, addresses many of the limitations associated with current BCI technology. The successful one-month in vivo recording of neuronal signals highlights the device's long-term stability and biocompatibility. The flexibility and low bending stiffness of the implant are crucial for minimizing tissue damage and eliciting a reduced inflammatory response, potentially leading to improved signal quality and longevity. This work advances the field of BCI technology, paving the way for safer and more effective neural implants for both research and clinical applications.

This study successfully demonstrated a novel MEMS-fabricated flexible neural implant with an ultrathin PI substrate, exhibiting excellent mechanical flexibility and biocompatibility. The device showed promising results in in vivo experiments, with stable neuronal signal recording for one month. This flexible design minimizes tissue damage during implantation and improves the long-term performance of BCI devices. Future research could focus on optimizing the electrode design for improved signal quality, exploring different polymer materials for enhanced biocompatibility, and conducting longer-term in vivo studies to evaluate the device's performance over extended periods.

The current study utilized a relatively small sample size for in vivo testing. Longer-term in vivo studies are needed to fully assess the chronic effects of the implant on brain tissue and the stability of the signal recordings over a more extended timeframe. Further investigations could explore the device's performance across different brain regions and species. The biocompatibility of the chosen polyimide, while promising, requires further assessment through more extensive cytotoxicity and chronic inflammatory response assays. While the 500nm thickness significantly enhances flexibility, it may compromise the mechanical strength of the implant. Further optimization of the balance between flexibility and robustness is warranted.