Ultra-sensitive measurement of brain penetration with microscale probes for brain machine interface considerations

Obaid, Abdulmalik; Wu, Yu-Wei; Hanna, Mina-Elraheb; W, Nix; Ding, Jihui; Melosh, Nicholas A.

doi:10.1101/454520

Cited by 28 publications

(50 citation statements)

References 41 publications

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“…This causes problems if the maximal force is below the force needed for insertion. Measurements have been made for different types of electrodes (Sharp et al, 2009;Casanova et al, 2014;Fekete et al, 2015), and recently a quantitative study was undertaken to understand the penetration mechanics of microwires specifically (Obaid et al, 2018). In our experiments, 15-20 μm wires could be inserted into the cortex several millimetres deep without support.…”

Section: Discussionmentioning

confidence: 99%

CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings

Kollo

Racz

Hanna

et al. 2019

Preprint

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SummaryMammalian brains consist of 10s of millions to 100s of billions of neurons operating at millisecond time scales, of which current recording techniques only capture a tiny fraction. Recording techniques capable of sampling neural activity at such temporal resolution have been difficult to scale: The most intensively studied mammalian neuronal networks, such as the neocortex, show layered architecture, where the optimal recording technology samples densely over large areas. However, the need for application-specific designs as well as the mismatch between the threedimensional architecture of the brain and largely two-dimensional microfabrication techniques profoundly limits both neurophysiological research and neural prosthetics.Here, we propose a novel strategy for scalable neuronal recording by combining bundles of glass-ensheathed microwires with large-scale amplifier arrays derived from commercial CMOS of in-vitro MEA systems or high-speed infrared cameras. High signal-to-noise ratio (<20 μV RMS noise floor, SNR up to 25) is achieved due to the high conductivity of core metals in glass-ensheathed microwires allowing for ultrathin metal cores (down to <1 μm) and negligible stray capacitance. Multi-step electrochemical modification of the tip enables ultra-low access impedance with minimal geometric area and largely independent of core diameter. We show that microwire size can be reduced to virtually eliminate damage to the blood-brain-barrier upon insertion and demonstrate that microwire arrays can stably record single unit activity.Combining microwire bundles and CMOS arrays allows for a highly scalable neuronal recording approach, linking the progress of electrical neuronal recording to the rapid scaling of silicon microfabrication. The modular design of the system allows for custom arrangement of recording sites. Our approach of employing bundles of minimally invasive, highly insulated and functionalized microwires to lift a 2-dimensional CMOS architecture into the 3rd dimension can be translated to other CMOS arrays such as electrical stimulation devices.

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Section: Discussionmentioning

confidence: 99%

CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings

Kollo

Racz

Hanna

et al. 2019

Preprint

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“…The maximum free length was limited by the material properties and buckling force threshold of the microwires. For example, 18 µm diameter tungsten wires with lengths of > 5 mm are feasible, while for 20 µm gold wires, lengths greater than 3 mm are likely to buckle upon insertion 41 . Different tip shapes are also possible through polishing or etching the ends of the wires (Fig S3eg).…”

Section: Microwire Bundlesmentioning

confidence: 99%

“…Alternatively, the wires could be individually electrosharpened 42 to form a <100 nm radius tip, then bundled together afterwards. Studies measuring the force of microwire insertion into brain tissue have found microwire size and electrosharpening play an important role in the amount of brain dimpling during insertion 41 .…”

Section: Microwire Bundlesmentioning

confidence: 99%

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

Obaid

Hanna

et al. 2019

Preprint

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Multi-channel electrical recordings of neural activity in the brain is an increasingly powerful method revealing new aspects of neural communication, computation, and prosthetics. However, while planar silicon-based CMOS devices in conventional electronics scale rapidly, neural interface devices have not kept pace. Here, we present a new strategy to interface silicon-based chips with three-dimensional microwire arrays, providing the link between rapidly-developing electronics and high density neural interfaces. The system consists of a bundle of microwires mated to large-scale microelectrode arrays, such as camera chips. This system has excellent recording performance, demonstrated via single unit and local-field potential recordings in isolated retina and in the motor cortex or striatum of awake moving mice. The modular design enables a variety of microwire types and sizes to be integrated with different types of pixel arrays, connecting the rapid progress of commercial multiplexing, digitisation and data acquisition hardware together with a three-dimensional neural interface. Figure 2: Microwire bundle fabrication. a, Fabrication procedure of microwire bundles. (i) Individual microwires are electrically insulated with a robust ceramic or polymeric coating. (ii) A sacrificial layer of parylene-C (PaC) is coated onto the wires to provide spacing. (iii) If desired, the tips of the microwires can be polished to an angular tip, or electrosharpened. (iv) The wires are then bundled together, either by spooling the wire, or mechanical aggregation. The wires naturally pack in a honeycomb array. (v)The bundle is infiltrated with biomedical epoxy to hold the wires together, then the top (proximal) end polished for mating to the CMOS chip. (vi) The proximal end is etched 10-20 µm to mate to the CMOS chip and the distal end of the wires is released by etching with oxygen plasma, allowing each wire to penetrate individually. A threaded collet is added to hold the bundle. b, A backscatter SEM of an individual microwire with a PtIr conductive core and 45 µm PaC coating (a, ii). c, The wires pack into a honeycomb structure, and epoxy is infiltrated in between to fill the gaps (a, v). d, The proximal end of a bundle of 177 20 µm Au wires with 100 µm spacing after etching to expose the conductive wire. e, The predicted volumetric displacement of bundles of microwires as a function of wire-to-wire distance, determined by the wire size and sacrificial coating thickness (t). This assumes a perfect hexagonal packing fraction of ~90.69%. For 15 µm wires with 100 µm spacing, the volume displaced is 2%. f, The distal end of a bundle of 600 7.5µm W wires coated with 1 µm of glass after etching to remove the PaC and embedded epoxy. g,h, The distal end (PtW 20 µm wires, 100 µm spacing) can be shaped with single wire precision to simultaneously access different depths in the tissue.

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“…Maximum insertion force was measured at the time of penetration, which was taken as the first absolute maximum of the force curve that preceded the first approximately infiniteslope curve characteristic of membrane penetration (Sridharan et al, 2013, Obaid et al, 2018. In a few cases, a slightly higher force was measured after initial penetration.…”

Section: In Vivo Insertion Force Measurementsmentioning

confidence: 99%

“…For a shuttle made of a given material, with length determined by the depth of the target brain area, a lower limit on the allowable device diameter is calculable by Euler's critical load equation. A larger diameter device will have a higher critical load to more likely penetrate the meninges, but is not desirable because it will compress a greater area of brain tissue on insertion and disrupt more vasculature (Obaid et al, 2018). One way to enable insertion of a device without increasing its diameter is to reduce the effective force on the device (i.e., to lower the required insertion force) by fabricating a sharper tip (Sharp et al, 2009, Bjornsson et al, 2006, Edell et al, 1992, Jensen et al, 2006.…”

Section: Introductionmentioning

confidence: 99%

A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain

Joo

Fan

Chen

et al. 2019

Preprint

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Electrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma. Durotomy increases brain swelling, vascular damage, and surgical time. Insertion using a bracing shuttle results in additional vascular damage and brain compression, which increase with device diameter; while a higher-diameter shuttle will have a higher critical load and more likely penetrate dura, it will damage more brain parenchyma and vasculature. One way to penetrate the intact dura and limit tissue compression without increasing shuttle diameter is to reduce the force required for insertion by sharpening the shuttle tip. We describe a novel design and fabrication process to create silicon insertion shuttles that are sharp in three dimensions and can penetrate rat dura, for faster, easier, and less damaging implantation of polymer arrays. Sharpened profiles are obtained by reflowing patterned photoresist, then transferring its sloped profile to silicon with dry etches. We demonstrate that sharpened shuttles can reliably implant polymer probes through dura to yield high quality single unit and local field potential recordings for at least 95 days. On insertion directly through dura, tissue compression is minimal. This is the first demonstration of a rat dural-penetrating array for chronic recording. This device obviates the need for a durotomy, reducing surgical time and risk of damage to the blood-brain barrier. This is an improvement to state-of-the-art flexible polymer electrode arrays that facilitates their implantation, particularly in multi-site recording experiments. This sharpening process can also be integrated into silicon electrode array fabrication.

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Ultra-sensitive measurement of brain penetration with microscale probes for brain machine interface considerations

Cited by 28 publications

References 41 publications

CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings

CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain

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