Professor Hong-gyu Park’s research team has published an article in Nano Letters.

By overcoming existing limitations, its findings are expected to be applied to various types of biological research and medical treatment.

A research team led by Professor Hong-gyu Park and Research Professor Jung-min Lee of the Department of Physics succeeded in observing long-term activity of single neurons by syringe-injecting mesh electronic nanoprobes into the brains of live mice.

The research was carried out in collaboration with Professor Charles M. Lieber at Harvard University and published on August 14 in the international journal Nano Letters (IF: 12.279).

- Authors: Hong-gyu Park (corresponding author, Korea University), Jung-min Lee (first author, Korea University), Charles M. Lieber (corresponding author, Harvard University)

- Research title: Nanoenabled direct contact interfacing of syringe-injectable mesh electronics. Nano Letters 19, 5818-5826 (2019).

▲ Professor Hong-gyu Park (left), Research Professor Jung-min Lee (right)

To explore the complexity of the brain, we need a way to measure all the changes that occur within the brain: spacewise from tens of nanometers of individual synapses to several centimeters interconnecting parts of the brain; and timewise from single-action transpositions within several milliseconds to long-term changes that are related to development/learning/memory/diseases. The electrophysiology probes developed so far consist of silicon-based electronics or arrays of metallic microwire electrodes, allowing simultaneous observation of hundreds to thousands of neurons using single-neuron spatial and temporal resolutions. However, such a rigid and inflexible probe not only causes chronic immune responses when it is inserted into the brain, but also disturbs long-term and stable observation of neuronal signals since the probe moves within the soft biological tissues.

To understand the important functions of neurons, effective and long-term observation of neuronal signals is required. For this, a new nanoprobe technology has been developed to stably inject probes into the brains of live mice. This nanoprobe, which is designed to look and feel like real neural tissue, consists of mesh electronics and is highly flexible with its three-dimensional (3D) open macroporous structure. Moreover, the size of the nanoprobe is similar to that of a neuron. Thus, the design features of this probe not only minimize immune responses, but also allow seamless integration between the electronic and neural networks which improves biocompatibility. In addition to measuring bio-signals with high yields, it is also possible to stably track single-unit neurons for long periods of time.

For better application, the input/output (I/O) pads of the nanoprobe are designed to be very flexible, allowing them to connect to external electrodes through capillary force without any additional pressure or heating. In addition, both sides of the new I/O pads are coated with metal, so that they can be connected to external electrodes on any side. Systematic studies have been conducted to lower the contact resistance of the electrode interface and make it more flexible. In particular, experiments have proved that the electrode interface can be formed with a high yield without shorting the adjacent channels. Moreover, the direct contact method has been newly applied in this study to connect 32 channels of mesh electronic probes to external electrodes more efficiently. Both in-vitro and in-vivo experiments have proved that all channels were electrically well connected. Furthermore, experiments with 32-channel nanoprobes implanted in live mice and consistent tracking of single-unit neural activity for over 2 months without any loss of channel recordings have proved the long-term stability of the direct contact interface method.

This study is especially meaningful because it uses multiple mesh electronic nanoprobes to track and observe neural activity at high yields in many channels. It is anticipated that the direct contact electrode interface developed through this research may be applied to other flexible electronic devices and used for a variety of biological research and medical treatments.

▲ Schematics illustrating the direct contact I/O interface of mesh electronic nanoprobes 

implanted in the brain of live mice