Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids

Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids

14 May 2024 | Yan Wu, Jinhao Cheng, Jie Qi, Chen Hang, Ruihua Dong, Boon Chuan Low, Hanry Yu, Xingyu Jiang
A flexible and stretchable 128-channel mesh neuro-interface (mMPC) based on a liquid metal-polymer conductor (MPC) was developed to record neural activity from human hippocampal organoids (hHOs). The mMPC, composed of gallium-indium (GaIn) alloy and elastic polymers (thermoplastic polyurethane, TPU, and polyurethane, PU), was designed to conform to the surface of hHOs and enable non-invasive electrical signal detection. The mMPC features high stretchability (up to 500%), flexibility, and excellent electrical performance, allowing it to maintain conductivity even under significant strain. A conductive polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), was deposited on the electrode surface to enhance stability and reduce impedance. The mMPC was fabricated using a soft lithography process, involving three PDMS patterns for the conductor, bottom substrate, and top insulating layers. The final device consists of TPU, PU, and liquid metal, with no PDMS components. The mMPC was integrated with hHOs to form a hippocampal cyb-organoid platform, enabling the recording of neural signals from the hHOs. Under Wnt3a and SHH activator induction, hHOs produced HOPX⁺ and PAX6⁺ progenitors and ZBTB20⁺ PROX1⁺ dentate gyrus (DG) granule neurons. The transcriptomic signatures of hHOs showed high similarity to the developing human hippocampus. The mMPC successfully detected neural activities, including spike rates, synchronization, and oscillatory network activity, from the hHOs. The mMPC's flexibility and stretchability allowed it to maintain contact with the hHOs, enabling high-throughput detection of neural signals. The mMPC's performance was compared with traditional planar devices, demonstrating its potential for recording neural signals from 3D models. The hHOs were generated from human induced pluripotent stem cells (hiPSCs) using a modified culture protocol that included Wnt3a and SHH signals to inhibit the expansion of the choroid plexus (ChP) and promote hippocampal fate. The hHOs exhibited markers of hippocampal development, including PAX6⁺ progenitors, HOPX⁺ progenitors, and ZBTB20⁺ PROX1⁺ granule neurons. Single-cell RNA sequencing revealed the presence of excitatory neurons (ExN), inhibitory neurons (InN), immature neurons (ImmN), neural progenitor cells (NPCs), astrocytes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes in the hHOs. The hHOs showed a high similarity to the human hippocampus up to 22 gestational weeks (GWA flexible and stretchable 128-channel mesh neuro-interface (mMPC) based on a liquid metal-polymer conductor (MPC) was developed to record neural activity from human hippocampal organoids (hHOs). The mMPC, composed of gallium-indium (GaIn) alloy and elastic polymers (thermoplastic polyurethane, TPU, and polyurethane, PU), was designed to conform to the surface of hHOs and enable non-invasive electrical signal detection. The mMPC features high stretchability (up to 500%), flexibility, and excellent electrical performance, allowing it to maintain conductivity even under significant strain. A conductive polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), was deposited on the electrode surface to enhance stability and reduce impedance. The mMPC was fabricated using a soft lithography process, involving three PDMS patterns for the conductor, bottom substrate, and top insulating layers. The final device consists of TPU, PU, and liquid metal, with no PDMS components. The mMPC was integrated with hHOs to form a hippocampal cyb-organoid platform, enabling the recording of neural signals from the hHOs. Under Wnt3a and SHH activator induction, hHOs produced HOPX⁺ and PAX6⁺ progenitors and ZBTB20⁺ PROX1⁺ dentate gyrus (DG) granule neurons. The transcriptomic signatures of hHOs showed high similarity to the developing human hippocampus. The mMPC successfully detected neural activities, including spike rates, synchronization, and oscillatory network activity, from the hHOs. The mMPC's flexibility and stretchability allowed it to maintain contact with the hHOs, enabling high-throughput detection of neural signals. The mMPC's performance was compared with traditional planar devices, demonstrating its potential for recording neural signals from 3D models. The hHOs were generated from human induced pluripotent stem cells (hiPSCs) using a modified culture protocol that included Wnt3a and SHH signals to inhibit the expansion of the choroid plexus (ChP) and promote hippocampal fate. The hHOs exhibited markers of hippocampal development, including PAX6⁺ progenitors, HOPX⁺ progenitors, and ZBTB20⁺ PROX1⁺ granule neurons. Single-cell RNA sequencing revealed the presence of excitatory neurons (ExN), inhibitory neurons (InN), immature neurons (ImmN), neural progenitor cells (NPCs), astrocytes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes in the hHOs. The hHOs showed a high similarity to the human hippocampus up to 22 gestational weeks (GW
Reach us at info@study.space