journal article·2019-09Open access

Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue

Max J. Cotler, Erin B. Rousseau, Khalil B. Ramadi, Joshua Fang, Ann M. Graybiel, Robert Langer, Michael J. Cima

Small· Volume 15· Issue 37

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Neuroscience and Neural Engineering · Neurological disorders and treatments · 3D Printing in Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA

Harvard‐MIT Program in Health Sciences and Technology Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA

McGovern Institute for Brain Research Department of Brain and Cognitive Sciences Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA

Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA

Department of Materials Science and Engineering Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA

Funding

National Science Foundation · National Institute of Biomedical Imaging and Bioengineering · National Cancer Institute

References (65)

Show source-provided references
1. 10.1016/j.neuron.2018.07.02210.1016/j.neuron.2018.07.022 ↗
2. 10.1038/nn.308810.1038/nn.3088 ↗
3. 10.1152/jn.00625.201110.1152/jn.00625.2011 ↗
4. 10.1038/mp.2014.210.1038/mp.2014.2 ↗
5. 10.1093/cercor/bhv10010.1093/cercor/bhv100 ↗
6. 10.1038/nature1247510.1038/nature12475 ↗
7. 10.1016/S0188-4409(00)00060-610.1016/S0188-4409(00)00060-6 ↗
8. Thomas G. P. · Med. Devices: Evidence Res. · 2015 · 8 · 405
9. 10.1111/epi.1374010.1111/epi.13740 ↗
10. 10.3389/fnint.2011.0006910.3389/fnint.2011.00069 ↗
11. 10.1093/brain/awu10210.1093/brain/awu102 ↗
12. 10.1038/nrn110510.1038/nrn1105 ↗
13. 10.1016/j.neuron.2005.02.01410.1016/j.neuron.2005.02.014 ↗
14. 10.1016/j.biopsych.2009.09.01310.1016/j.biopsych.2009.09.013 ↗
15. 10.1016/j.biopsych.2008.08.02910.1016/j.biopsych.2008.08.029 ↗
16. 10.1016/j.nurt.2007.11.00610.1016/j.nurt.2007.11.006 ↗
17. 10.1021/cn500256e10.1021/cn500256e ↗
18. 10.1006/exnr.1998.698310.1006/exnr.1998.6983 ↗
19. 10.1016/S0006-8993(03)03023-310.1016/S0006-8993(03)03023-3 ↗
20. 10.1016/j.jneumeth.2005.08.01510.1016/j.jneumeth.2005.08.015 ↗
21. 10.1016/S0165-0270(98)00031-410.1016/S0165-0270(98)00031-4 ↗
22. Kipke D. R. · Electr. Eng. · 2003 · 11 · 1
23. 10.3389/fneng.2014.0000710.3389/fneng.2014.00007 ↗
24. 10.1038/s41551-017-0154-110.1038/s41551-017-0154-1 ↗
25. 10.1016/j.smim.2007.11.00410.1016/j.smim.2007.11.004 ↗
26. 10.1126/scitranslmed.300327610.1126/scitranslmed.3003276 ↗
27. 10.1039/C6LC01411A10.1039/C6LC01411A ↗
28. 10.1088/1741-2560/9/4/04602010.1088/1741-2560/9/4/046020 ↗
29. 10.1109/JSEN.2005.85787710.1109/JSEN.2005.857877 ↗
30. 10.1016/j.expneurol.2005.04.02010.1016/j.expneurol.2005.04.020 ↗
31. 10.1038/s41598-017-02107-210.1038/s41598-017-02107-2 ↗
32. 10.1073/pnas.171375611410.1073/pnas.1713756114 ↗
33. 10.1126/scitranslmed.aan274210.1126/scitranslmed.aan2742 ↗
34. Schwerdt H. · 2015
35. 10.1039/C6LC01398H10.1039/C6LC01398H ↗
36. 10.1038/s42003-018-0147-y10.1038/s42003-018-0147-y ↗
37. 10.1016/S1474-4422(11)70039-410.1016/S1474-4422(11)70039-4 ↗
38. 10.1002/polb.2216910.1002/polb.22169 ↗
39. 10.1073/pnas.180437211510.1073/pnas.1804372115 ↗
40. Minhas D. · 2009 · 25810.1109/IEMBS.2009.5334006 ↗
41. 10.1142/S2424905X1750001510.1142/S2424905X17500015 ↗
42. Webster R. J. · IEEE Int. Conf. Rob. Autom. · 2005 · 3599
43. 10.1109/TMECH.2005.84830010.1109/TMECH.2005.848300 ↗
44. 10.1007/3-540-45468-3_11510.1007/3-540-45468-3_115 ↗
45. Majewicz A. · IEEE Int. Conf. Rob. Autom. · 2010 · 2010 · 2068
46. 10.1109/TBME.2012.220474910.1109/TBME.2012.2204749 ↗
47. 10.1109/TBME.2014.233430910.1109/TBME.2014.2334309 ↗
48. 10.1109/TMECH.2014.236599910.1109/TMECH.2014.2365999 ↗
49. 10.1109/TRO.2007.89897210.1109/TRO.2007.898972 ↗
50. 10.1016/j.medengphy.2013.11.00610.1016/j.medengphy.2013.11.006 ↗
51. 10.1109/TBME.2012.223000110.1109/TBME.2012.2230001 ↗
52. 10.1115/1.403378310.1115/1.4033783 ↗
53. 10.1109/TRO.2014.230763310.1109/TRO.2014.2307633 ↗
54. 10.1016/j.conengprac.2017.03.00410.1016/j.conengprac.2017.03.004 ↗
55. Engh J. A. · 2006 · 103
56. Engh J. A. · 2006 · 559
57. 10.1227/NEU.0b013e3181ec155110.1227/NEU.0b013e3181ec1551 ↗
58. Ramezanpour H. · J. Biomed. Phys. Eng. · 2015 · 5 · 207
59. 10.1109/TRO.2016.262333910.1109/TRO.2016.2623339 ↗
60. Gardiner T. W. · Contemp. Top. Lab. Anim. Sci. · 1999 · 38 · 56
61. 10.3389/fneng.2014.0000710.3389/fneng.2014.00007 ↗
62. 10.5214/ans.0972.7531.20030910.5214/ans.0972.7531.200309 ↗
63. 10.3171/jns.2004.101.2.031410.3171/jns.2004.101.2.0314 ↗
64. 10.1021/bm005583j10.1021/bm005583j ↗
65. 10.3171/JNS/2008/109/11/087410.3171/JNS/2008/109/11/0874 ↗