Genetically encoded optogenetic effectors, inhibitors, and fluorescent indicators are important tools in neuroscience. Optogenetic techniques enable precise manipulation of neural circuits using light. However, light attenuation poses challenges to delivering spatially shaped light that controls the range of stimulation to deep brain regions.
According to MEMS Consulting, recently, researchers from the Max Planck Institute of Microstructure Physics in Germany have overcome this challenge through an implantable silicon neural probe with integrated microelectrodes and nanophotonic circuits fabricated by a foundry. This probe can emit designed beam patterns with sufficiently high power to stimulate neural activities ranging from cellular spikes to full-network responses. In vivo experiments evaluated probes that emit low-divergence beams or planar light sheets, both of which can selectively stimulate neurons at different depths. A comparison of the spike responses they induced shows that, compared with the low-divergence probe, the light sheet probe can induce a higher degree of firing rate fatigue at lower light intensities. The light sheet probe can also induce seizures in the hippocampus of a mouse model of epilepsy while keeping the temperature rise within 1 °C. Integrating additional devices, such as wavelength multiplexers and photodetectors, can enable a multi-functional implant for multi-modal brain activity mapping. The related research results were published in the journal npj Biosensing under the title "Implantable nanophotonic neural probes for integrated patterned photostimulation and electrophysiological recording".
The nanophotonic neural probe system proposed in this paper is shown in the figure below. The probe is passive and uses an off-chip laser source and recording electronics to minimize the risk of tissue heating. Each probe is connected to an external laser scanning system and an electrophysiological data acquisition circuit board for simultaneous optical stimulation and electrophysiological recording. The nanophotonic neural probes were fabricated on 200-mm-diameter silicon wafers using deep ultraviolet (DUV) lithography at the Advanced Micro Foundry.
Conceptual diagram of the nanophotonic neural probe system
This probe consists of a single layer of silicon nitride (SiN) for optical waveguides and three layers of aluminum (Al) metal wiring layers. Titanium nitride (TiN) is used to form biocompatible surface microelectrodes. Through the foundry's wafer back grinding process followed by post-processing polishing, the probe thickness can be reduced to 40 - 60 µm.
Overview of Neural Probes Integrated with Microelectrodes
To demonstrate the ability to customize the beam emission pattern, the researchers designed probes with two different gratings. The first type of probe, called the "low divergence (LD) probe", emits a low divergence beam from a single shank. One low divergence probe has 16 uniform gratings and 18 electrodes. The second type of probe, called the "light sheet (LS) probe", can emit a light sheet for full-network range optical stimulation at a specific depth. One light sheet probe has 4 probe shanks that are 4 mm long and 5 light sheet emitters. The light sheet is formed by the overlapping emission of 8 grating emitter arrays on the 4 probe shanks.
Characterization of the probes
In in vivo experiments, both the low-divergence probe and the light-sheet probe can selectively stimulate neurons at different depths of the cortex. The planar beam emission of the light-sheet probe provides a wider beam coverage, stimulating the neurons around the four probe shanks. Additionally, compared with the low-divergence probe, the light-sheet probe induces a stronger electrophysiological response at a lower output intensity, as evidenced by a stronger firing rate fatigue. Moreover, it can induce seizures in the hippocampus of epileptic mouse models while keeping the expected temperature increase below <1 °C.
Demonstration of spatially selective optogenetic stimulation using a light-sheet probe in awake and head-fixed mice.
In the epileptic mouse model, the light-sheet probe induces seizures in the CA1 region of the hippocampus through optogenetics.
As far as the researchers know, this work is the first demonstration of a nanophotonic neural probe. It customizes the beam emission pattern through the combined advantages of high output power and a flexible emitter design, enabling a full-network response to optogenetic stimulation. The light sheet probe proposed in this paper can serve as a basic building block to advance the development of multifunctional neural probes for studying full-network activity, especially seizure dynamics in epilepsy research.
In summary, the researchers have demonstrated a foundry-provided photonic integrated circuit (PIC) platform for developing implantable neural probes capable of simultaneously performing electrophysiological recordings and patterned light stimulation. The uniqueness of this probe lies in its utilization of integrated nanophotonics technology to customize the light emission pattern for stimulating different tissue volumes. In addition to emitting low-divergence light beams to induce cellular spike activity, the integrated light sheet emitter, which distributes light emission along the probe shank to generate planar illumination, can extend the application of silicon photonic neural probes to full-network interrogation at specific depths. In the future, further development of these probes to support higher power emission and achieve widespread light distribution could be used to stimulate larger brain regions in rodents or animals with larger brains. Through foundry manufacturing, the researchers expect that a new generation of multifunctional neural implants for multimodal neural stimulation and recording can be mass-produced for the widespread dissemination of this technology to the neuroscience community.
Paper link:
https://www.nature.com/articles/s44328-025-00024-3