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Small. 2019 Jun 11:e1901459. doi: 10.1002/smll.201901459. [Epub ahead of print]

Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue.

Author information

1
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA.
2
Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA.
3
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA.
4
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA.
5
Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA.

Abstract

Enhanced understanding of neuropathologies has created a need for more advanced tools. Current neural implants result in extensive glial scarring and are not able to highly localize drug delivery due to their size. Smaller implants reduce surgical trauma and improve spatial resolution, but such a reduction requires improvements in device design to enable accurate and chronic implantation in subcortical structures. Flexible needle steering techniques offer improved control over implant placement, but often require complex closed-loop control for accurate implantation. This study reports the development of steerable microinvasive neural implants (S-MINIs) constructed from borosilicate capillaries (OD = 60 µm, ID = 20 µm) that do not require closed-loop guidance or guide tubes. S-MINIs reduce glial scarring 3.5-fold compared to prior implants. Bevel steered needles are utilized for open-loop targeting of deep-brain structures. This study demonstrates a sinusoidal relationship between implant bevel angle and the trajectory radius of curvature both in vitro and ex vivo. This relationship allows for bevel-tipped capillaries to be steered to a target with an average error of 0.23 mm ± 0.19 without closed-loop control. Polished microcapillaries present a new microinvasive tool for chronic, predictable targeting of pathophysiological structures without the need for closed-loop feedback and complex imaging.

KEYWORDS:

borosilicate; drug delivery; needle steering; neuroengineering

PMID:
31183933
DOI:
10.1002/smll.201901459

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