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Our Innovation
Encasing a BCI in a nanocarrier has the potential to breach the blood-brain barrier without using invasive surgical techniques such as craniotomies. While nanocarriers and BCIs exist, they do so independently. N4NO integrates these technologies to achieve safer BCI insertion for neuroprosthetic use, addressing concerns regarding the size, attachment, tracking, and implementation of BCIs to make this idea a reality.
Neural Dust
Invasive BCIs are ≈1000x larger than typical nanocarriers, which range between 1 and 1000nm. Bridging this gap, neural dust “motes” are minuscule BCIs, smaller than a grain of sand, that wirelessly operate inside the brain to record neural signals and transmit them to an external ultrasound transceiver [11, 12].
Transport: Mechanisms and Pathway
N4NO employs intrathecal administration to bypass the blood-brain barrier, using polymeric micelles, a type of nanocarrier, to encase, protect, and deliver neural dust to the brain.
Blood-Brain Barrier
The Blood-Brain Barrier, or the BBB, is a semipermeable membrane that allows the entry of small lipophilic molecules while restricting the entry of larger ones [13]. As such, the BBB prevents toxins from entering the brain while simultaneously restricting neurotherapeutics.
Nanocarriers
Nanocarriers encase a therapeutic, mimicking endogenous molecules recognized by BBB transporters to gain entry into the brain, enabling an encapsulated therapeutic to bypass rejection mechanisms and reach their intended targets within the central nervous system [14]. N4NO employs polymeric micelles specifically for their high stability and biocompatibility [15] and their suitability in the encasement of water-insoluble drugs [16].
Pathways
While the BBB restricts the entrance of foreign substances into the brain, it is not present everywhere in the brain, namely in the circumventricular organs [17]. N4NO injects a liquid mixture of neutral dust encased in polymeric micelles into the thecal sac, traveling via CSF to reach the brain, bypassing the BBB altogether. Nonetheless, nanocarriers still prove beneficial in protecting its encased material and enhancing its timely release.
Attachment and Tracking
Nerve Cuff
Once the nanocarrier dissolves upon entry to the brain, the neural dust will be released and must attach to a specific nerve. N4NO makes use of nerve cuffs, consisting of a flexible polymer atop a hydrogel. When in contact with fluids, such as ones present in the brain, the swelling of the hydrogel triggers a self-folding mechanism that wraps the cuff around a nerve without damage. The electrodes, attached to the flexible polymer layer, come directly in contact with the nerve, with the hydrogel wrapping around the outside [18].
Flourescence
Through surface modification, fluorescent probes are conjugated to the polymeric micelle, enabling the labeling of the nanocarrier via fluorescence microscopy [19]. This conjugation enables the tracking of the nanocarrier, helping neurosurgeons to see if the N4NO neural dust arrives at its intended destination.
Our Prototype
