Flexible, multifunctional neural probe with liquid metal enabled, ultra-large tunable stiffness for deep-brain chemical sensing and agent delivery

Ximiao Wen; Bo Wang; Shan Huang; Tingyi Leo Liu; Meng-Shiue Lee; Pei-Shan Chung; Yu Ting Chow; I-Wen Huang; Harold G Monbouquette; Nigel T Maidment; Pei-Yu Chiou

doi:10.1016/j.bios.2019.01.060

Flexible, multifunctional neural probe with liquid metal enabled, ultra-large tunable stiffness for deep-brain chemical sensing and agent delivery

Biosens Bioelectron. 2019 Apr 15:131:37-45. doi: 10.1016/j.bios.2019.01.060. Epub 2019 Feb 7.

Authors

Ximiao Wen¹, Bo Wang², Shan Huang³, Tingyi Leo Liu⁴, Meng-Shiue Lee⁵, Pei-Shan Chung⁶, Yu Ting Chow¹, I-Wen Huang⁷, Harold G Monbouquette⁷, Nigel T Maidment⁸, Pei-Yu Chiou⁹

Affiliations

¹ Department of Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, CA, USA.
² Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, CA, USA.
³ Department of Biological Chemistry, University of California at Los Angeles, CA, USA.
⁴ Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst, MA, USA.
⁵ Department of Mechanical Engineering, National Chiao Tung University, Hsinchu, Taiwan.
⁶ Department of Bioengineering, University of California at Los Angeles, CA, USA.
⁷ Department of Chemical and Biomolecular Engineering, University of California at Los Angeles, CA, USA.
⁸ Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, CA, USA. Electronic address: nmaidmen@g.ucla.edu.
⁹ Department of Mechanical and Aerospace Engineering, University of California at Los Angeles, Los Angeles, CA, USA; Department of Bioengineering, University of California at Los Angeles, CA, USA. Electronic address: pychiou@seas.ucla.edu.

Abstract

Flexible neural probes have been pursued previously to minimize the mechanical mismatch between soft neural tissues and implants and thereby improve long-term performance. However, difficulties with insertion of such probes deep into the brain severely restricts their utility. We describe a solution to this problem using gallium (Ga) in probe construction, taking advantage of the solid-to-liquid phase change of the metal at body temperature and probe shape deformation to provide temperature-dependent control of stiffness over 5 orders of magnitude. Probes in the stiff state were successfully inserted 2 cm-deep into agarose gel "brain phantoms" and into rat brains under cooled conditions where, upon Ga melting, they became ultra soft, flexible, and stretchable in all directions. The current 30 μm-thick probes incorporated multilayer, deformable microfluidic channels for chemical agent delivery, electrical interconnects through Ga wires, and high-performance electrochemical glutamate sensing. These PDMS-based microprobes of ultra-large tunable stiffness (ULTS) should serve as an attractive platform for multifunctional chronic neural implants.

Keywords: Drug delivery; Electrochemical biosensors; Flexible electronics; Liquid metal; Neural probes.

MeSH terms

Animals
Biosensing Techniques*
Brain / drug effects*
Brain / pathology
Electrodes, Implanted
Gallium / administration & dosage*
Gallium / chemistry
Humans
Polymers / chemistry
Rats
Temperature

Substances

Polymers
Gallium

Grants and funding

R01 NS087494/NS/NINDS NIH HHS/United States