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项目总结：《2025年大脑报告》，目标是《制作大脑运作的动态图像》 2通过开发和应用改进的方法来大规模监测神经活动“是直接的 3由此应用程序解决。神经像素探测器(Jun等人，《自然》2017)表明， 具有连续、致密、可编程位置的4通道计数硅杆在 5神经活动监测(典型设备的单位为100‘S与10’S)。神经像素NXT将增加 6通过优化和部署一种新的平台技术来大幅提高高容量刀柄的效用 7神经记录，直接到数字。神经像素虽然比现有技术具有革命性，但它有一个集成的探头 8个用于放大和数字化的“底座”和一个数字接口板(头台)，均位于 9脑。总而言之，这些组件在大脑上方的拥挤限制了小腿的数量 10在一只实验动物身上使用。后续的项目已经在进行中，以缓解这种拥挤和负担 11这样，我们预计2个神经像素探头(768个通道的记录容量)可以自由地在 12只移动的、被拴住的老鼠。虽然这代表了一个实质性的改善，但它仍然远远低于大脑的广度 13满足上述抱负的记录，即“制作一幅大脑运作的动态图像”。 14在展示神经像素小腿性能的基础上，我们建议对底座进行优化 15个电子器件，因此具有~768个通道的探头的底座将为5mm2(底座缩小18倍 与神经像素相比，每个通道16个区域，与神经像素2.0相比缩小6倍)，不需要额外的 17数字接口板(头级)，取而代之的是在探头和高压头之间有一根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。这个较小的探测器 19底座将允许将其缩小，以便每个探头都将充当可以并排平铺的“单位柄” 20制成“梳子”，并将梳子堆叠成小腿的2维阵列，产生密集的3维阵列 21个可编程记录点。我们预计&gt；16个站点(9600个站点/通道，全部处于活动状态)的容量 22只小鼠，40个小腿(40,000多个可编程站点，26,000多个通道)，以及多达100个小腿(450,000个 23个可编程位置，76.800个通道)在非人灵长类中。工作方案首先要优化：1)设计 24个直接数字记录通道像素，用于大小/噪声折衷；以及2)数据集线器，最多允许12个 25个探头由一根输出电缆提供服务。有了这些信息，就会产生一个“单位小腿”家族， 26准备出售给研究团体，可以固定在各种各样的记录几何图形。 27在能够长期生产和负担得起成本的环境中进行这些开发将确保 28提供广泛的服务。

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