Organic Semiconducting Nanoparticles for Neural Interfacing—Combining Neuroprotective Drug Delivery with Optically Generated Bioelectronic Charge for Enhanced Neuron Growth and Stimulation

When and Where

May 11, 2022
5:00pm - 7:00pm

Hawai'i Convention Center, Level 1, Kamehameha Exhibit Hall 2 & 3

Presenter

Matthew Griffith

Connor Sherwood

Rafael Crovador

Natalie Holmes

Julie Cairney

Paul Dastoor

Alan Brichta

Rebecca Lim

Co-Author(s)

Matthew Griffith¹,Connor Sherwood²,Rafael Crovador²,Natalie Holmes¹,Julie Cairney¹,Paul Dastoor²,Alan Brichta²,Rebecca Lim²

The University of Sydney¹,The University of Newcastle²

Abstract

Matthew Griffith¹,Connor Sherwood²,Rafael Crovador²,Natalie Holmes¹,Julie Cairney¹,Paul Dastoor²,Alan Brichta²,Rebecca Lim²

The University of Sydney¹,The University of Newcastle²

Implantable neurostimulation devices play a key role in treating many serious injuries and diseases by providing a direct therapeutic link to the nervous system. This enables brain stimulation for treatment of Parkinson’s disease and epilepsy, nerve guidance and regeneration to remedy spinal cord injury, and retinal prosthetic devices that could cure blindness.[1] To address such issues, new bioelectronic systems that can deliver electrical stimulation to nerve cells are required. Although silicon microelectronics and metal electrodes have been the historic gold standard for bioelectronic interfaces, their use in clinical practice is limited. The main obstacles to further translation of these devices include a low biocompatibility that reduces in vivo lifetimes, a mechanical rigidity that is poorly matched with soft tissue, causing inflammation and ineffective electrical contact, and a requirement for costly external power supplies to deliver current.[2] These issues result in indiscriminate tissue activation, with a consequent lack of spatial selectivity.[3] In this work, we report our recent efforts to simultaneously address these issues by combining soft carbon-based organic conductors and nanoscale science to build new bioelectrodes that allow optical neurostimulation without external power. Our approach creates bioelectronic interfaces from organic conductors that can be formed into customized nanoparticles with established solution-based chemistry methodologies. This approach enables the stimulating electrodes to be combined with targeted pharmaceutical factors in the fabrication procedure, which subsequently optimise connections to the neural network when released in-vivo.[4] We will discuss how we tuned the optoelectronic properties of the organic nanoparticles to cover standard red, green, and blue spectral regions, allowing spectrally selective platforms for neurostimulation. These conductors are turned into electroactive inks, and subsequently fabricated into pixelated arrays using inkjet printing. This approach establishes a new low-cost manufacturing methodology that is generally applicable to other organic materials and can be used for a variety of bioelectronic devices, creating a new manufacturing paradigm for healthcare. We demonstrate both the anatomical and functional biocompatibility of neural tissue with our organic bioelectronic systems using immunolabelling with neuronal marker MAP2 and visualisation with epifluorescence microscopy to detect neurons cultured on the organic conductors. We demonstrate the controlled release of drugs from the organic conductive nanoparticles, aiding in precise spatial delivery of pharmaceutical factors. Finally, we employ whole-cell patch clamp electrophysiology recordings to demonstrate an exciting result; purely optical neurostimultation of dorsal root ganglion nerve cells. We demonstrate that the organic conductors can trigger changes in the nerve cell membrane potentials via a capacitive coupling mechanism, the efficacy of which can be improved by judicious selection of the device architecture.[5] References: [1]. B. Zhu, S. C. Luo, H. Zhao, H. A. Lin, J. Sekine, A. Nakao, C. Chen, Y. Yamashita, H. H. Yu; Nat. Commun., 2014, 5, 4523. [2]. T. Someya, Z. Bao, G. G. Malliaras; Nature, 2016, 540, 379. [3]. C. Liao, M. Zhang, M. Y. Yao, T. Hua, L. Li, F. Yan; Adv. Mater., 2015, 27, 7493. [4]. R. Crovador, H. Heim, S. Cottam, K. Feron, V. Bhatia, F. Louie, C. P. Sherwood, P. C. Dastoor, A. M. Brichta, R. Lim, M. J. Griffith; ACS Appl. Bio Mater., 2021, 4, 6338. [5]. C. P. Sherwood, D. C. Elkington, M. R. Dickinson, W. J. Belcher, P. C. Dastoor, K. Feron, A. M. Brichta, R. Lim, M. J Griffith; IEEE J. Selected Topics Quant. Electron. 2021, 27, 1.