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Direct integration of cortical electrodes by conducting polymers deposited in-viv

通过体内沉积的导电聚合物直接集成皮质电极

基本信息

批准号：
8451847
负责人：
DAVID C MARTIN
金额：
$ 24.96万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2015-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Project Summary / Abstract - Perhaps the most important problem limiting the performance and utility of electronic biomedical devices that are implanted in tissue is the reactive response near the electrode that limits performance over extended periods of time. In the cortex, this is known to involve the activation of microglia and astrocytes, and the associated die-off of target cells (neurons) in a region of ~100 microns proximal to the probe surface. Strategies to overcome this problem have included the use of anti-inflammatory agents and neurotrophic factors. However, it is not clear that inflammatory agents will work over the long term. Attracting the neurons to the electrode is also a strategy that may not work well, since the inorganic electrode surface represents an interface between the hard metallic or semiconducting engineered device and the much softer organic tissue, and is thus inevitably a mechanically unstable environment that is dangerous for cell viability. It would therefore be useful if there were some alternative means to create nanoscale, electronically active filaments that were an extension of the metal electrodes, providing an efficient means of communication across the reactive scar and out into the surrounding tissue. Here we propose a method that may accomplish this by the direct, in- vivo polymerization of conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT). PEDOT is a conjugated polymer that is effective at facilitating charge transport between metallic electrodes and ionically conductive tissue. In previous work in our laboratory, we have shown that PEDOT coatings can help to improve the performance of biomedical devices such as microfabricated cortical probes in vivo. We have also demonstrated that PEDOT can be electrochemically polymerized around living cells both in-vitro and in-vivo. In slice cultures, we have shown that PEDOT can be grown out and into cortical tissue for 1000 microns or more, much larger than the ~100 micron size typical of the reactive cell layer. However many questions remain about the detailed methods of polymerization, including monomer delivery rates, influence of healing, and the viability and remodeling of cells in the polymerization zone. In this project we will investigate the in-vivo polymerization of PEDOT into living tissue, and will evaluate its impact on the performance of the biomedical devices of interest. We will investigate the role of wound healing around the probe on the subsequent polymerization and associated cell physiology in the reactive zone by waiting for different periods of time before initiating the reaction. We will focus our attention on microfabricated cortical electrodes of interest to the Center for Neural Communications Technology at the University of Michigan, directed by Daryl Kipke. This method has the potential to revolutionize the performance of a wide variety of implantable electronic biomedical devices including cortical probes, retinal implants, deep brain stimulators, and cardiac pacemakers. If this novel research eventually proves to be successful, there is considerable potential to move these methods from the laboratory to further development. Certain aspects of this work are related to inventions disclosed to the University of Michigan Technology Transfer Office, and under commercial development by Biotectix LLC, a spin-off company. Prof. Martin is a Co- Founder and Chief Scientific Officer for Biotectix LLC (www.biotectix.com).

描述（由申请人提供）：项目总结/摘要-可能限制植入组织中的电子生物医学设备的性能和实用性的最重要问题是电极附近的反应性响应，这限制了长时间的性能。在皮质中，已知这涉及小胶质细胞和星形胶质细胞的激活，以及距离探针表面约100微米区域内靶细胞（神经元）的相关死亡。克服这个问题的策略包括使用抗炎剂和神经营养因子。然而，目前尚不清楚炎症因子是否会长期起作用。将神经元吸引到电极上也是一种可能效果不佳的策略，因为无机电极表面代表了硬金属或半导体工程设备与软得多的有机组织之间的界面，因此不可避免地是一个机械不稳定的环境，对细胞活力是危险的。因此，如果有一些替代手段来创建纳米级的电子活性细丝，其是金属电极的延伸，提供穿过反应性瘢痕并进入周围组织的有效通信手段，则将是有用的。在这里，我们提出了一种方法，可以实现这一点的直接，在体内聚合的导电聚合物，如聚（3，4-乙撑二氧噻吩）（PEDOT）。PEDOT是一种共轭聚合物，可有效促进金属电极和离子传导组织之间的电荷传输。在我们实验室以前的工作中，我们已经表明PEDOT涂层可以帮助改善生物医学设备的性能，如体内的微制造皮质探针。我们还证明了PEDOT可以在体外和体内活细胞周围电化学聚合。在切片培养中，我们已经证明PEDOT可以生长出并进入皮质组织1000微米或更长，远大于反应性细胞层典型的~100微米尺寸。然而，关于聚合的详细方法仍存在许多问题，包括单体递送速率、愈合的影响以及聚合区中细胞的活力和重塑。在本项目中，我们将研究PEDOT在活组织中的体内聚合，并将评估其对感兴趣的生物医学设备性能的影响。我们将通过在开始反应之前等待不同的时间段来研究探针周围的伤口愈合对随后的聚合和反应区中的相关细胞生理学的作用。我们将把注意力集中在密歇根大学神经通信技术中心感兴趣的微加工皮层电极上，该中心由Daryl Kipke领导。这种方法有可能彻底改变各种植入式电子生物医学设备的性能，包括皮层探针，视网膜植入物，深部脑刺激器和心脏起搏器。如果这项新的研究最终被证明是成功的，那么将这些方法从实验室转移到进一步发展的潜力是相当大的。这项工作的某些方面与密歇根大学技术转让办公室披露的发明有关，并由分拆公司Biotectix LLC进行商业开发。Martin教授是Biotectix LLC（www.biotectix.com）的联合创始人兼首席科学官。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Structural, chemical and electrochemical characterization of poly(3,4-ethylenedioxythiophene) (PEDOT) prepared with various counter-ions and heat treatments.

DOI：
10.1016/j.polymer.2011.01.042
发表时间：
2011-03-01
期刊：
POLYMER
影响因子：
4.6
作者：
King, Zachary A.;Shaw, Charles M.;Spanninga, Sarah A.;Martin, David C.
通讯作者：
Martin, David C.

Highly Aligned Poly(3,4-ethylene dioxythiophene) (PEDOT) Nano- and Microscale Fibers and Tubes.

DOI：
10.1016/j.polymer.2012.10.057
发表时间：
2013-01-24
期刊：
POLYMER
影响因子：
4.6
作者：
Feng, Zhang-Qi;Wu, Jinghang;Cho, Whirang;Leach, Michelle K.;Franz, Eric W.;Naim, Youssef I.;Gu, Zhong-Ze;Corey, Joseph M.;Martin, David C.
通讯作者：
Martin, David C.

Significant enhancement of PEDOT thin film adhesion to inorganic solid substrates with EDOT-acid.

使用 EDOT 酸显着增强 PEDOT 薄膜对无机固体基材的附着力。

DOI：
10.1021/acsami.5b03350
发表时间：
2015
期刊：
ACS applied materials & interfaces
影响因子：
9.5
作者：
Wei,Bin;Liu,Jinglin;Ouyang,Liangqi;Kuo,Chin-Chen;Martin,DavidC
通讯作者：
Martin,DavidC

Synthesis and characterization of bicontinuous cubic poly(3,4-ethylene dioxythiophene) gyroid (PEDOT GYR) gels.

DOI：
10.1039/c4cp04426f
发表时间：
2015-02-21
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
0
作者：
Cho W;Wu J;Shim BS;Kuan WF;Mastroianni SE;Young WS;Kuo CC;Epps TH 3rd;Martin DC
通讯作者：
Martin DC

Stiffness, strength and adhesion characterization of electrochemically deposited conjugated polymer films.