Periodic Reporting for period 1 - ChroMOS (Toward monolithic CMOS based neural probes for stable chronic recording and brain machine interfaces)
Reporting period: 2020-11-01 to 2022-10-31
The brain influences all aspects of our life, is the most complex organ of the body and is composed by billions of cells, mainly neurons and glia. Neurological conditions are the second leading cause of death worldwide and the leading cause of Disability Adjust Life Years, accordingly to World Health Organization. It’s key to better understand and monitor the brain in order to prevent and cure brain related diseases, such as stroke, dementia, epilepsy, depression, drug addiction, and Parkinson and Alzheimer disease. The introduction of high-density implantable neural probes based on complementary metal–oxide semiconductor (CMOS) technology, such as the SiNAPS probes developed in our lab, is a big step forward in neuroscience. These new probes provide simultaneous access to thousands of single neurons in different brain circuits, introducing hundreds of closely spaced microelectrodes into the substrate for recording extracellular bioelectrical signals. However, when a device is implanted in the brain, it triggers tissue-reactions to protect the brain from the device, called foreign body response (FBR). Such FBR leads to device loss of recording quality over time and eventually to its complete failure. An emerging hypothesis to minimize tissue-reactions and improve chronic stability of implantable probes consists in downscaling the cross-sectional sizes of their shafts (implanted part) as well as the overall system size. Downscaling the size of conventional implantable probes is at the cost of a drastically reduced number of recording sites due to technological limitations, which leads to limited information retrieved from the brain. The ChroMOS project explored the key advantages of monolithic CMOS-based neural probes together with the optimization of circuits, materials and microfabrication processes to reduce the size of the probe to micro-wire like dimensions (≈ 30 µm diameter) while maintaining a high number of recording sites.
The ChroMOS project started by developing bare silicon probes with shank cross-sectional sizes of 23 to 83 µm in width, 3 to 5 mm in length and 15 µm in thickness. This probes were mechanically characterized by nanoindentation techniques and insertion force measurements. A setup for the measurement of the insertion forces involved in the implantation was developed with micro-Newton resolution. The development of such probes allowed to optimize the microfabrication processes, the handling of very small devices and to define the target dimensions for the final ChroMOS probes. Next, in collaboration of Dr. G.N. Angotzi, the CMOS circuit of the ChroMOS probes was designed to meet the target dimensions. The technology node 180 nm from TSMC was used in a multi-project-wafer (MPW) run to realize chips of ≈ 8 x 3 mm in size. After receiving these devices from the foundry, I successfully optimized a MEMS processing flow in order to realize structured ChroMOS probes. The use of MPW processes rather than full-wafer CMOS processes allowed to drastically drop the prototyping costs of these devices. However, microfabrication of small samples is particularly challenging because all the clean-room equipment is typically conceived for wafer substrates and handling of the devices between processing steps becomes more complicated. In order to improve the process reliability and mitigate these issues, a research spray-coater equipment was acquired by the lab, and I optimized the necessary photoresists for the process. This allowed to realize the unprecedented ChroMOS probes that integrate 64 electrodes in a 26 µm wide and 20 µm thick shank.
Finally, the ChroMOS probes were mounted on a dedicated PCB and wire bonded. Electrophysiological recordings were performed by adapting the SiNAPS acquisition system and software developed in the lab. Bench-top and in-vivo experiments indicate a significant gain in SNR when compared with the SiNAPS probes. Commercially available SiNAPS probes (currently commercialized by Plexon Inc. and NeuroNexus) were used for comparison with the ChroMOS probes realized in this project.
The ChroMOS project was presented in several recognized conferences both from engineering and neuroscience fields, such as the 11th International IEEE EMBS Conference on Neural Engineering (NER), the Micro and Nano Engineering conference (MNE), the Annual IEEE International Electron Devices Meeting (IEDM) and the Neuroscience from the Society for Neuroscience (SFN). The results were also disseminated to the general public by setting a public website (https://sinapsprobes.eu/(opens in new window)) by presentation at “Festival della Scienza” to undergraduate students and by media public interviews.
Finally, the ChroMOS probes were mounted on a dedicated PCB and wire bonded. Electrophysiological recordings were performed by adapting the SiNAPS acquisition system and software developed in the lab. Bench-top and in-vivo experiments indicate a significant gain in SNR when compared with the SiNAPS probes. Commercially available SiNAPS probes (currently commercialized by Plexon Inc. and NeuroNexus) were used for comparison with the ChroMOS probes realized in this project.
The ChroMOS project was presented in several recognized conferences both from engineering and neuroscience fields, such as the 11th International IEEE EMBS Conference on Neural Engineering (NER), the Micro and Nano Engineering conference (MNE), the Annual IEEE International Electron Devices Meeting (IEDM) and the Neuroscience from the Society for Neuroscience (SFN). The results were also disseminated to the general public by setting a public website (https://sinapsprobes.eu/(opens in new window)) by presentation at “Festival della Scienza” to undergraduate students and by media public interviews.
The ChroMOS probes are unique and represent a new tool for neuroscience in pursue to “unveil” the secrets of the brain. It is the first planar neural probe that includes 64 electrodes in a “micro-wire” like shank. The 26 µm wide and 20 µm thick shank of such a planar silicon probe is unprecedented and sets a new dimensional threshold in the neuroengineering of implantable intracortical neural probes. Importantly, the reduced tissue reaction to the implant observed has a high potential to increase the longevity of the brain monitoring device, opening new possibilities for neuroscience research and approaches for clinical applications. At clinical level, I expect a first impact in refractory cases of Parkinson’s disease patients, psychiatric disorders such as major depression and obsessive-compulsive disorder, which affects around 500 million people worldwide. But these needle-like devices might also have relevant potential in applications targeting the peripheral nervous system (PNS).