Abstract
Wirelessly powered microdevices are being miniaturized to improve safety, longevity, and spatial resolution in a wide range of biomedical applications. Some wireless microdevices have reached a point where they can be injected whole into the central nervous system. However, the state-of-the-art floating microdevices have not yet been tested in chronic brain applications, and there is a growing concern that the implants might migrate through neural tissue over time. Using a 9.4T MRI scanner, we attempt to address the migration question by tracking ultra-small devices injected in different areas of the brain (cortico-subcortical) of rats over 5 months. We demonstrate that injectable microdevices smaller than 0.01 mm3 remain anchored in the brain at the targeted injection site over this time period. Based on CD68 (microglia) and GFAP (astrocytes) immunoreactivity to the microdevice, we hypothesize that glial scar formation is preventing the migration of chronically implanted microdevices in the brain over time.
Highlights
Injectable wirelessly powered devices, or microdevices, play a major role in many emerging biomedical applications including neural monitoring (Lee et al, 2020; Sigurdsson et al, 2020; Zhang et al, 2020), neural stimulation (Freeman et al, 2017; Khalifa et al, 2019), and temperature sensing (Cortese et al, 2020; Shi et al, 2021)
Our study aims at answering the following questions: (1) Will intracortical microdevices (≤0.01 mm3) drift by more than 200 μm within a period of 4.5 months? (2) Does the site of injection and size of the microbead impact migration or anchoring? (3) What could be causing migration or anchoring? 200 μm is chosen as the lower limit due to the resolution limit of the MRI scanner used in this study
If floating wireless microdevices are to become a major technology for interfacing with the central nervous system, we can no longer ignore the important open question as to whether the spatial stability of the microdevices after injection can be preserved under chronic conditions
Summary
Injectable wirelessly powered devices, or microdevices, play a major role in many emerging biomedical applications including neural monitoring (Lee et al, 2020; Sigurdsson et al, 2020; Zhang et al, 2020), neural stimulation (Freeman et al, 2017; Khalifa et al, 2019), and temperature sensing (Cortese et al, 2020; Shi et al, 2021). Microdevices in this case should not be confused with micro/nanoparticles (Chen et al, 2018; Le et al, 2019; Kozielski et al, 2021) as the latter does not include integrated circuitry. Only a handful of academic research labs have managed to microfabricate brain devices small enough to be fully injectable, as researchers continue to make progress in reducing the microdevice volume using innovative wireless powering (Karimi et al, 2017) and packaging techniques (Khalifa et al, 2017a), Tracking Microdevices in the Brain Using MRI future developments will no doubt result in more epicortical implants transform into intracortical implants (Barbruni et al, 2020; Yang et al, 2020)
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