# Curved Implantation of Flexible Microelectrode Arrays for High-Density Mapping of Nonlinear Brain Structures and Circuits

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $237,914

## Abstract

Project Summary
The brain is nature’s most sophisticated signal-processing system. Unlike human-made integrated circuits, the
brain circuits organize in a complex three-dimensional and intertwined manner, which makes it challenging to
spatially resolve neuronal activities. Among all available neural recording technologies, penetrating neural
probes hold great promise and are vital to neuroscience research. In common practice, neural probes are linearly
inserted into the brain to map the local activity, which, however, can only probe a single spot in the targeted brain
region. An entire circuit or structure can be mapped by deploying multiple probes, but the spatial resolution is
modest. To date, how to spatially resolve single-unit activities from nonlinearly organized brain structures and
circuits is still a challenge. Here, we propose to fill the technological gap via a nonlinear probe implantation
modality. In contrast to the conventional linear implantation, we will conformally deploy high-density
microelectrode arrays along designated curved brain circuits or structures with minimal surgical lesions.
Ultraflexible neural probes with high electrode density will be designed accordingly to obtain the optimal
nonlinear implantation outcome. The proposed technology will be fulfilled via three Aims: In Aim 1, we will
develop the implantation apparatus and optimize the probe design using an in-vitro test platform; In Aim 2, we
will evaluate and optimize the nonlinear implantation in vivo and characterize the surgical lesion and
biocompatibility of the probes; in Aim 3, we will systematically examine the nonlinear probe in single-unit
neuronal recording and demonstrate its usefulness in studying the place codes of the mouse hippocampus. In
our preliminary study, we validated the feasibility of the proposed method by deploying nonlinear probes along
the longitudinal axis of the mouse hippocampus, a well-known nonlinear structure in the brain. Precise targeting,
low surgical lesion, and chronic single-unit tracking were shown. The technology, if successful, will significantly
increase the spatial resolution of brain mapping along nonlinear circuits or brain structures, make the hard-to-
access brain regions within reach, offer alternative routes toward designated brain regions, and offer a
generalizable approach for other brain interventions. In all, we believe the nonlinear delivery of neural probes
enabled by this project will be a valuable modality complementary to the conventional linear implantation for
both basic and translational neurosciences.

## Key facts

- **NIH application ID:** 10835360
- **Project number:** 1R21EY035955-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Dingchang Lin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $237,914
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835360

## Citation

> US National Institutes of Health, RePORTER application 10835360, Curved Implantation of Flexible Microelectrode Arrays for High-Density Mapping of Nonlinear Brain Structures and Circuits (1R21EY035955-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10835360. Licensed CC0.

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