Understanding the brain requires tools that can follow neural activity across many scales: from millisecond electrical spikes in individual neurons to brain-wide circuit dynamics that change over months, years, and even a lifetime. However, existing technologies still face major limitations in achieving long-term, brain-wide recording at single-cell and single-spike resolution in mammals.
A research team from Harvard University reviewed recent progress in implantable microelectronics and proposed a technological roadmap toward brain-wide lifetime electrophysiology in mammals. The review was published in Nano Research on July 14, 2026.
The team highlights that mammalian brain activity is highly dynamic across life stages. During development, neural activity helps regulate processes such as cell proliferation, migration, synapse formation, and circuit refinement. In adulthood and aging, neural activity supports learning, memory, and behavior, while abnormal activity is closely related to neurological and psychiatric disorders.
"An ideal electrophysiological technology would allow researchers to record from the mammalian brain across the whole brain and across the lifetime, while still resolving individual neurons and individual spikes," said Hao Sheng, first author of the review. "Implantable microelectronics provide one of the most promising paths toward this goal, but several engineering challenges still need to be solved."
The review organizes these challenges into several major categories. First, devices must adapt to large changes in brain size and shape, especially during development. Second, they must reduce tissue responses such as gliosis, which can degrade signal quality over time. Third, they must maintain stable electrical performance in biofluids for long-term implantation. Finally, future systems must handle large-scale data acquisition, transmission, and processing.
The review compares passive and active electrode architectures. Passive electrodes can be made ultra-thin, soft, and stretchable, making them attractive for long-term and developmental studies. Active electrodes, by contrast, integrate local amplification and multiplexing, enabling higher channel counts and improved signal quality, but they also introduce challenges related to stiffness, power consumption, and encapsulation stability.
The authors also discuss emerging strategies in materials, device architecture, implantation, wireless transmission, spike sorting, and closed-loop processing. Together, these advances may support future neural interfaces capable of tracking single-neuron activity across distributed brain regions throughout life.
The review was authored by Hao Sheng, Paul Le Floch, Thomas S. Blum, and Jia Liu from the John A. Paulson School of Engineering and Applied Sciences, Harvard University, under the supervision of Jia Liu.
DOI Link:
https://doi.org/10.26599/NR.2026.94908864
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.
