An integrated brain-machine interface platform with thousands of channels

Brain-machine interfaces (BMIs) hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical BMIs have not yet been widely adopted, in part because modest channel counts have limited their potential. In this white paper, we describe Neuralink’s first steps toward a scalable high-bandwidth BMI system. We have built arrays of small and
flexible electrode “threads”, with as many as 3,072 electrodes per array distributed across 96 threads.
We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute.
Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization:
the package for 3,072 channels occupies less than (23 × 18.5 × 2) mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously.
This system has achieved a spiking yield of up to 85.5 % in chronically implanted electrodes. Neuralink’s approach to BMI has unprecedented packaging density and scalability in a clinically relevant package.

1 Introduction
Brain-machine interfaces (BMIs) have the potential to help people with a wide range of clinical disorders. For example, researchers have demonstrated human neuroprosthetic control of computer cursors [1, 2, 3], robotic limbs [4, 5], and
speech synthesizers [6] using no more than 256 electrodes. While these successes suggest that high fidelity information transfer between brains and machines is possible, development of BMI has been critically limited by the inability to
record from large numbers of neurons. Noninvasive approaches can record the average of millions of neurons through the skull, but this signal is distorted and nonspecific [7, 8]. Invasive electrodes placed on the surface of the cortex can
record useful signals, but they are limited in that they average the activity of thousands of neurons and cannot record signals deep in the brain [9]. Most BMI’s have used invasive techniques because the most precise readout of neural representations requires recording single action potentials from neurons in distributed, functionally-linked ensembles [10].
Microelectrodes are the gold-standard technology for recording action potentials, but there has not been a clinically translatable microelectrode technology for large-scale recordings [11]. This would require a system with material properties
that provide high biocompatibility, safety, and longevity. Moreover, this device would also need a practical surgical approach and high-density, low-power electronics to ultimately facilitate fully-implanted wireless operation.
Most devices for long-term neural recording are arrays of electrodes made from rigid metals or semiconductors [12, 13, 14, 15, 16, 17, 18]. While rigid metal arrays facilitate penetrating the brain, the size, Young’s modulus and bending stiffness
mismatches between stiff probes and brain tissue can drive immune responses that limit the function and longevity of these devices [19, 11]. Furthermore, the fixed geometry of these arrays constrains the populations of neurons that
can be accessed, especially due to the presence of vasculature.
An alternative approach is to use thin, flexible multi-electrode polymer probes [20, 21]. The smaller size and increased flexibility of these probes should offer greater biocompatibility. However, a drawback of this approach is that thin polymer probes are not stiff enough to directly insert into the brain; their insertion must be facilitated by stiffeners [22, 21], injection [23, 24] or other approaches [25], all of which are quite slow [26, 27].

To satisfy the functional requirements for a high-bandwidth BMI, while taking advantage of the properties of thin-film devices, we developed a robotic approach,where large numbers of fine and flexible polymer probes are efficiently and independently inserted across multiple brain regions [28].
Here, we report Neuralink’s progress towards a flexible, scalable BMI that increases channel count by an order of magnitude over prior work. Our system has three main components: ultra-fine polymer probes (section 2 of this report), a
neurosurgical robot (section 3), and custom high-density electronics (section 4). We demonstrate the rapid implantation of 96 polymer threads, each thread with 32 electrodes for a total of 3,072 electrodes.
We developed miniaturized custom electronics that allow us to stream full broadband electrophysiology data simultaneously from all these electrodes (section 5). We packaged this system for long-term implantation and developed
custom online spike detection software that can detect action potentials with low latency. Together, this system serves as a state-of-the-art research platform and a first prototype towards a fully implantable human BMI.

We have developed a custom process to fabricate minimally displacive neural probes that employ a variety of biocompatible thin film materials. The main substrate and dielectric used in these probes is polyimide, which encapsulates
a gold thin film trace. Each thin film array is composed of a “thread” area that features electrode contacts and traces and a “sensor” area where the thin film interfaces with custom chips that enable signal amplification and acquisition.
A wafer-level microfabrication process enables high-throughput manufacturing of these devices. Ten thin film devices are patterned on a wafer, each with 3,072 electrode contacts.
Each array has 48 or 96 threads, each of those containing 32 independent electrodes. Integrated chips are bonded to the contacts on the sensor area of the thin film using a flip-chip bonding process. One goal of this approach is to maintaina small thread cross-sectional area to minimize tissue displacement in the brain. To achieve this, while keeping channel count high, stepper lithography and other microfabrication techniques are used to form the metal film at sub-micron
We have designed and manufactured over 20 different thread and electrode types into our arrays; two example designs are shown in panels A and B of fig. 1. We have fabricated threads ranging from 5 to 50 μm in width that incorporate
recording sites of several geometries (fig. 1). Thread thickness is nominally 4 to 6 μm, which includes up to three layers of insulation and two layers of conductor. Typical thread length is approximately 20 mm. To manage these long, thin
threads prior to insertion, parylene-c is deposited onto the threads to form a film on which the threads remain attached until the surgical robot pulls them off. Each thread ends in a (16 × 50) μm2 loop to accommodate needle threading.
Since the individual gold electrode sites have small geometric surface areas (fig. 1C), we use surface modifications to lower the impedance for electrophysiology and increase the effective charge-carrying capacity of the interface (fig. 1D).
Two such treatments that we have used are the electrically conductive polymer poly-ethylenedioxythiophene doped with polystyrene sulfonate (PEDOT:PSS) [29, 30] and iridium oxide (IrOx) [31, 32]. In bench-top testing we have
achieved impedances of 36.97 ± 4.68 kΩ (n = 257 electrodes) and 56.46 ± 7.10 kΩ (n = 588) for PEDOT:PSS and IrOx, respectively. The lower impedance of PEDOT:PSS is promising, however the long-term stability and biocompatibility
of PEDOT:PSS is less well established than for IrOx. These techniques and processes can be improved and further extended to other types of conductive electrode materials and coatings.

3 Robot

Thin-film polymers have previously been used for electrode probes [21], but their low bending stiffness complicates insertions. Neuralink has developed a robotic insertion approach for inserting flexible probes [28], allowing rapid and
reliable insertion of large numbers of polymer probes targeted to avoid vasculature and record from dispersed brain regions. The robot’s insertion head is mounted on 10 μm globally accurate, 400 mm × 400 mm × 150 mm travel threeaxis
stage, and holds a small, quick-swappable, “needle-pincher” assembly (fig. 2, fig.3A).
The needle is milled from 40 μm diameter tungsten-rhenium wire-stock electrochemically etched to 24 μm diameter along the inserted length (fig. 2A). The tip of the needle is designed both to hook onto insertion loops—for transporting
and inserting individual threads—and to penetrate the meninges and brain tissue. The needle is driven by a linear motor allowing variable insertion speeds and rapid retraction acceleration (up to 30,000 mm s−2) to encourage separation of the probe from the needle. The pincher is a 50 μm tungsten wire bent at the tip and driven both axially and rotationally (fig. 2B). It serves as support for probes during transport and as a guide to ensure that threads are inserted along the needle path. Figure 4 shows a sequence of photographs of the insertion process into an agarose brain proxy.
The inserter head also holds an imaging stack (fig. 3E–G) used for guiding the needle into the thread loop, insertion targeting, live insertion viewing, and insertion verification. In addition, the inserter head contains six independent light
modules, each capable of independently illuminating with 405 nm, 525 nm and 650 nm or white light (fig. 3C). The 405 nm illumination excites fluorescence from polyimide and allows the optical stack and computer vision to reliably
localize the (16 × 50) μm2 thread loop and execute sub-micron visual serving to guide, illuminated by 650 nm the needle through it. Stereoscopic cameras, software based monocular extended depth of field calculations, and illumination
with 525 nm light allow for precise estimation of the location of the cortical surface.
The robot registers insertion sites to a common coordinate frame with landmarks on the skull, which, when combined with depth tracking, enables precise targeting of anatomically defined brain structures. An integrated custom software
suite allows pre-selection of all insertion sites, enabling planning of insertion paths optimized to minimize tangling and strain on the threads. The planning feature highlights the ability to avoid vasculature during insertions, one of the key
advantages of inserting electrodes individually. This is particularly important, since damage to the blood-brain barrier is thought to play a key role in the brain’s inflammatory response to foreign objects [33].
The robot features an auto-insertion mode, which can insert up to 6 threads (192 electrodes) per minute. While the entire insertion procedure can be automated, the surgeon retains full control, and if desired, can make manual microadjustments
to the thread position before each insertion into the cortex. The neurosurgical robot is compatible with sterile shrouding, and has features to facilitate successful and rapid insertions such as automatic sterile ultrasonic cleaning of the needle. The needle pincher cartridge (NPC; fig. 2C) is the portion of the inserter head that makes direct contact with brain tissue and is a consumable that can be replaced mid-surgery in under a minute.

With this system, we have demonstrated an average of 87.1 ± 12.6 % (mean ± s.d.) insertion success rate over 19 surgeries.
In this study, precise manual adjustments were made to avoid microvasculature on the cortical surface, slowing total insertion time from the fastest possible. Even with these adjustments, the total insertion time for this study averaged
∼45 min, for an approximate insertion rate of 29.6 electrodes per minute (fig. 6). Insertions were made in a (4 × 7) mm2 bilateral craniotomy with >300 μm spacing between threads to maximize cortical coverage. This demonstrates
that robotic insertion of thin polymer electrodes is an efficient and scalable approach for recording from large numbers of neurons in anatomically defined brain regions.

Figure 4: 1. The inserter approaches the brain proxy with a thread. i. needle and cannula. ii. previously inserted thread.

  1. Inserter touches down on the brain proxy surface. 3. Needle penetrates tissue proxy, advancing the thread to the desired depth. iii. inserting thread. 4. Inserter pulls away, leaving the thread behind in the tissue proxy. iv. inserted

(to be continued)

Elon Musk & Neuralink

source 16/07/19

About sooteris kyritsis

Job title: (f)PHELLOW OF SOPHIA Profession: RESEARCHER Company: ANTHROOPISMOS Favorite quote: "ITS TIME FOR KOSMOPOLITANS(=HELLINES) TO FLY IN SPACE." Interested in: Activity Partners, Friends Fashion: Classic Humor: Friendly Places lived: EN THE HIGHLANDS OF KOSMOS THROUGH THE DARKNESS OF AMENTHE
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