Neuropixels NXT: Integrated Silicon Probes for Large Scale Extracellular Recording in Rodents and Primates

Neuropixels NXT：用于啮齿动物和灵长类动物大规模细胞外记录的集成硅探针

• 批准号: 10475277
• 负责人: TIMOTHY D HARRIS
• 金额: $ 381.45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10475277
• 关键词: 3-Dimensional; Acute; Address; Animals; Area; Arts; BRAIN initiative; Brain; Brain Diseases; Brain region; Cells; Chronic; Comb animal structure; Communities; Crowding; Development; Devices; Electronics; Electrophysiology (science); Engineering; Ensure; Environment; Family; Geometry; Goals; Head; Impairment; In Vitro; Letters; Light; Methods; Monitor; Mus; Nature; Neurons; Noise; Output; Performance; Phase; Photophobia; Preparation; Primates; Production; Rattus; Reporting; Research; Rodent; Sales; Side; Silicon; Site; Speed; System; Technology; Test Result; Testing; Thick; Update; Weight; Work; awake; base; cost; data hub; design; digital; experimental study; extracellular; improved; in vivo; integrated circuit; manufacturing scale-up; nonhuman primate; optogenetics; phase 1 designs; programs; prototype; relating to nervous system; transmission process; two-dimensional

1 Project Summary: The BRAIN 2025 Report, with the goal to “produce a dynamic picture of the functioning brain 2 by developing and applying improved methods for large-scale monitoring of neural activity” is directly 3 addressed by this application. The Neuropixels probe (Jun et al., Nature 2017) demonstrated that a high 4 channel count Si shank with continuous, dense, programmable sites yielded a large capacity increase in 5 monitoring of neural activity (100's vs. 10's of units for typical devices). Neuropixels NXT will increase 6 substantially the utility of that high capacity shank by optimizing and deploying a new platform technology for 7 neural recording, direct-to-digital. Neuropixels, while revolutionary over prior art, has an integrated probe 8 “base” for amplification and digitization and a digital interface board (head stage) that both reside above the 9 brain. Together, the crowding of these components above the brain limits the number of shanks that can be 10 used in one experimental animal. Follow-on projects are already underway to relieve this crowding and weight 11 such that we expect 2 Neuropixels probes (768 channels of recording capacity) could be used on a freely 12 moving, tethered mouse. While this represents a substantial improvement, it remains far short of the brain wide 13 recording that satisfies the above stated ambition to “produce a dynamic picture of the functioning brain”. 14 Building on the demonstrated performance of the Neuropixels shank, we propose to optimize the base 15 electronics so that a probe with ~768 channels would have a base of < 5mm2 (an 18x shrinkage of the base 16 area per channel compared to Neuropixels, and 6x shrinkage compared to Neuropixels 2.0), require no extra 17 digital interface board (head stage), and instead have a 6-conductor micro-cable between the probe and a high 18 speed data hub for digital transmission that can handle multiple probes simultaneously. This smaller probe 19 base will allow it to be made narrow so that each probe will act as a “unit shank” that can be tiled side-to-side 20 into a “comb”, and combs stacked into 2 dimensional arrays of shanks, yielding dense 3 dimensional arrays of 21 programmable recording sites. We project capacities of >16 shanks (9600 sites/channels, all active) in a 22 mouse, 40 shanks (40,000+ programmable sites, 26,000+ channels) in a rat, and up to 100 shanks (450,000 23 programmable sites, 76.800 channels) in a non-human primate. The work plan will first optimize: 1) the design 24 of the direct-to-digital recording channel pixel for size/noise tradeoff, and 2) the data hub to allow up to 12 25 probes to be served by a single output cable. With this information, a family of “unit shanks” will be produced, 26 ready for sale to the research community, which can be fixtured into a wide variety of recording geometries. 27 These developments in an environment capable of long term manufacture and affordable costs will ensure 28 wide availability.

1 项目摘要：《BRAIN 2025 报告》，目标是“生成大脑功能的动态图景” 2 通过开发和应用大规模神经活动监测的改进方法”直接 3 本申请所解决的问题。 Neuropixels 探针（Jun 等人，Nature 2017）证明，高 4 通道数硅柄具有连续、密集、可编程位点，可大幅提高容量 5 神经活动监控（典型设备的 100 个单位与 10 个单位）。 Neuropixels NXT 将增加 6 通过优化和部署新的平台技术，充分利用高容量刀柄 7 神经记录，直接数字化。 Neuropixels 虽然比现有技术具有革命性，但具有集成探针 8 个用于放大和数字化的“底座”以及一个数字接口板（头级），两者均位于 9 大脑。总之，这些部件在大脑上方的拥挤限制了可形成的小腿的数量。 10个用于一只实验动物。后续项目已经在进行中，以缓解这种拥挤和重量 11 这样我们预计 2 个 Neuropixels 探针（768 个通道的记录容量）可以在一个自由的 12 只移动的、系绳的鼠标。虽然这代表了一个实质性的进步，但它仍然远远低于全脑范围 13 条记录满足了上述“生成大脑功能的动态图像”的雄心。 14 基于 Neuropixels 柄的已展示性能，我们建议优化底座 15 个电子器件，因此具有约 768 个通道的探头的底座 < 5mm2（底座收缩 18 倍） 与 Neuropixel 相比，每个通道有 16 个区域，与 Neuropixel 2.0 相比，缩小了 6 倍），无需额外 17 数字接口板（头级），而是在探头和高电压之间有一条 6 芯微电缆 用于数字传输的 18 速数据集线器，可同时处理多个探头。这个较小的探头 19 底座将使其变窄，以便每个探针将充当可以左右平铺的“单元柄” 20 个“梳子”，梳子堆叠成 2 维梳柄阵列，产生密集的 3 维阵列 21 个可编程录音站点。我们预计容量> 16 shanks（9600个站点/频道，全部活跃） 大鼠体内有 22 个鼠标、40 个柄（40,000 多个可编程位点、26,000 多个通道），最多 100 个柄（450,000 个通道） 非人类灵长类动物中的 23 个可编程位点，76.800 个通道）。工作方案首先会优化：1）设计 24 个直接数字记录通道像素以实现尺寸/噪声权衡，2) 数据中心允许最多 12 个像素 一根输出电缆可连接 25 个探头。有了这些信息，将生产一系列“单位刀柄”， 26 准备出售给研究界，可以固定到各种记录几何形状中。 27 在能够长期制造且成本可承受的环境中的这些发展将确保 28 广泛可用性。

项目成果

An AC-Coupled 1st-order Δ-ΔΣ Readout IC for Area-Efficient Neural Signal Acquisition.

用于区域高效神经信号采集的交流耦合一阶 Ω-Ω 读出 IC。

• DOI: 10.1109/jssc.2023.3234612
• 发表时间: 2023
• 期刊: IEEE journal of solid-state circuits
• 影响因子: 5.4
• 作者: Yang,Xiaolin;Ballini,Marco;Sawigun,Chutham;Hsu,Wen-Yang;Weijers,Jan-Willem;Putzeys,Jan;Lopez,CarolinaMora
• 通讯作者: Lopez,CarolinaMora

Multi-day Neuron Tracking in High Density Electrophysiology Recordings using EMD.

使用 EMD 进行高密度电生理学记录中的多日神经元跟踪。

• DOI: 10.1101/2023.08.03.551724
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Yuan,AugustineXiaoran;Colonell,Jennifer;Lebedeva,Anna;Okun,Michael;Charles,AdamS;Harris,TimothyD
• 通讯作者: Harris,TimothyD