# Single-Die-Level MEMS Post-Processing for Prototyping CMOS-Based Neural Probes Combined with Optical Fibers for Optogenetic Neuromodulation

**Authors:** Gabor Orban, Alberto Perna, Matteo Vincenzi, Raffaele Adamo, Gian Nicola Angotzi, Luca Berdondini, João Filipe Ribeiro

PMC · DOI: 10.3390/mi17020159 · 2026-01-26

## TL;DR

This paper introduces a new MEMS post-processing method for CMOS neural probes that can be combined with optical fibers for optogenetics, enabling high-resolution brain monitoring.

## Contribution

A MEMS post-processing workflow for CMOS dies is developed, enabling material modification and layout shaping for neural probes.

## Key findings

- Spray-coating photolithography methods were optimized to suppress edge effects on small substrates.
- A 512-channel neural probe with a photoelectric shield was fabricated and showed >96% light-shielding effectiveness.
- In vivo experiments confirmed the probe's high-resolution electrophysiological measurement capability.

## Abstract

The integration of complementary metal–oxide–semiconductor (CMOS) and micro-electromechanical systems (MEMSs) technologies for miniaturized biosensor fabrication enables unprecedented spatiotemporal resolution in monitoring the bioelectrical activity of the nervous system. Wafer-level CMOS technology incurs high costs, but multi-project wafer (MPW) runs mitigate this by allowing multiple users to share a single wafer. Still, monolithic CMOS biosensors require specialized surface materials or device geometries incompatible with standard CMOS processes. Performing MEMS post-processing on the few square millimeters available in MPW dies remains a significant challenge. In this paper, we present a MEMS post-processing workflow tailored for CMOS dies that supports both surface material modification and layout shaping for intracortical biosensing applications. To address lithographic limitations on small substrates, we optimized spray-coating photolithography methods that suppress edge effects and enable reliable patterning and lift-off of diverse materials. We fabricated a needle-like, 512-channel simultaneous neural recording active pixel sensor (SiNAPS) technology based neural probe designed for integration with optical fibers for optogenetic studies. To mitigate photoelectric effects induced by light stimulation, we incorporated a photoelectric shield through simple modifications to the photolithography mask. Optical bench testing demonstrated >96% light-shielding effectiveness at 3 mW of light power applied directly to the probe electrodes. In vivo experiments confirmed the probe’s capability for high-resolution electrophysiological measurements.

## Full-text entities

- **Genes:** Zbtb8os (zinc finger and BTB domain containing 8 opposite strand) [NCBI Gene 67106] {aka 2010001H09Rik, 2310028N13Rik, Arch, Archm}
- **Diseases:** neurological disorders (MESH:D009461), injury to (MESH:D014947), tissue damage (MESH:D017695), infectious disease (MESH:D003141), gliosis (MESH:D005911)
- **Chemicals:** Ag (MESH:D012834), AgCl (MESH:C037548), Cu (MESH:D003300), boron (MESH:D001895), water (MESH:D014867), isoflurane (MESH:D007530), PEDOT:PSS (MESH:C533756), polymer (MESH:D011108), metal (MESH:D008670), Platinum (MESH:D010984), gold (MESH:D006046), NaCl (MESH:D012965), oxygen (MESH:D010100), H2SO4 (MESH:C033158), SF6 (MESH:D013459), CHF3 (MESH:C009554), Cr (MESH:D002857), Ti (MESH:D014025), acetone (MESH:D000096), Al (MESH:D000535), CMOS (-), silicon (MESH:D012825), graphene (MESH:D006108), ITO (MESH:C109984), SiO2 (MESH:D012822)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942394/full.md

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Source: https://tomesphere.com/paper/PMC12942394