CN109222905B - 颅内伤口愈合监测装置、其制备方法及应用 - Google Patents
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Abstract
本发明提供了一种颅内伤口愈合监测装置、其制备方法及应用,所述装置包括:柔性电极阵列和光声成像***。基于液态金属的柔性电极阵列,具有高生物安全性的同时具有较低的弹性模量,可以紧密贴合在皮层伤口表面,检测出高分辨率的脑电信号;光声成像***不仅检测精度高,对组织无损伤,而且安全方便,是医学成像辅助诊断的重要进步;结合柔性脑电极阵列与光声成像***,克服了颅内伤口无法观察的难题,实现颅内伤口的无创监测,其监测准确度甚至可以满足临床监测指标要求。
Description
技术领域
本发明属于颅内伤口监测领域,具体涉及一种颅内伤口愈合监测装置、其制备方法及应用。
背景技术
目前对于颅内创伤状况缺乏有效的监测手段,是临床治疗的一大难题。及时、准确地监测颅内伤口愈合情况,不仅有利于早期发现颅内伤口变化,提高治疗效果,而且对于临床诊断和指导治疗具有非常重要的意义。植入式脑电极可以有效监测脑组织电信号,从而可以根据脑电信号的变化判断伤口的愈合情况。其中脑电极阵列是监测脑电信号的重要脑机接口,可以在人脑与电子设备之间建立直接的交流通道,为伤口愈合状况提供重要的数据参考。然而,传统的植入式神经电极虽然可以获得较高的信噪比,但是容易对组织造成一定的损伤,例如商用的Michigan电极和Utah电极。近年来,新型的柔性脑电极阵列以其高分辨的信号检测和极低的组织损伤,已经成为神经科学领域研究的重点。
与此同时,随着医学成像技术的不断发展,医学成像技术为颅内伤口监测提供了强有力的技术支撑。常用的医学成像技术包括核磁共振成像技术(MRI)、X射线计算机断层扫描技术(CT)和光声成像技术(PAT)。在实际使用过程中,MRI成像需要借助于强大的磁场,而且生成图像的时间较长,无法实现对组织伤口的实时成像;CT成像在使用时产生大量的辐射,不可用于长时间观察。作为一种新兴的非侵入式成像技术,光声成像技术结合了光学成像和超声成像的优点,具有高对比度和高穿透深度的优良特性,可以提供清晰持续性的监测成像。
因此,结合柔性脑电极阵列与光声成像技术,寻求开发一种可以准确监测颅内伤口愈合状况的方法具有良好的研究与应用价值。
发明内容
因此,本发明的目的在于克服现有技术中的缺陷,提供一种颅内伤口愈合监测装置、其制备方法及应用。
在阐述本发明内容之前,定义本文中所使用的术语如下:
术语“PDMS”是指:聚二甲基硅氧烷。
为实现上述目的,本发明的第一方面提供了一种颅内伤口愈合监测装置,所述装置包括:柔性电极阵列和光声成像***。
根据本发明第一方面的装置,其中,所述光声成像***为近红外光声成像***;优选地,所述光声成像***包含脉冲激光器、超声波信号接收器和数据处理分析模块。
根据本发明第一方面的装置,其中,所述柔性电极阵列包括:基底,和在所述基底上纳米级或微米级液态金属颗粒汇聚而成的互联导线。
根据本发明第一方面的装置,其中,所述基底材料选自以下一种或多种:PDMS、Ecoflex、水溶性聚氨酯、聚乳酸、聚己内酯等高分子材料;优选为PDMS。
根据本发明第一方面的装置,其中,所述液态金属选自以下一种或多种:铟镓合金、镓铟锡合金、铋锡合金;优选为铟镓合金。
根据本发明第一方面的装置,其中,所述柔性电极阵列的制备方法包括以下步骤:
(1)将液态金属加入到有机溶剂中,将液态金属加工成微纳米颗粒,得到液态金属油墨;
(2)用步骤(1)制备的液态金属油墨绘制电极阵列图案;
(3)待溶剂挥发完全后,在印刷的电极图案上面浇铸预固化的基底材料,固化完全后,得到柔性电极阵列。
优选地,所述步骤(1)中,所述有机溶剂选自以下一种或多种:正癸醇、水、酒精、丙酮、N,N-二甲基甲酰胺、二氯甲烷、三氯甲烷、四氢呋喃;优选为正癸醇。
所述步骤(1)中,所述加工方法为超声和/或机械搅拌。
所述步骤(2)中,所述电极阵列图案绘制方法选自以下一种或多种:丝网印刷、喷墨打印、3D打印;优选为丝网印刷。
本发明的第二方面提供了第一方面所述的装置在制备用于监测伤口愈合的医疗产品中的应用。
本发明的目的在于克服现有技术存在的问题,针对颅内伤口愈合状况无法监测的严峻挑战,提供一种可以监测颅内伤口愈合状况的方法,该方法可以实现颅内伤口状况实时准确监测,为颅内创伤诊断提供参考,具有重大的临床意义及应用价值。
为了实现上述目的,本发明采用以下技术方案来实现:
利用柔性可拉伸的脑电极阵列探测颅内伤口组织的脑电信号,再结合光声成像技术获得伤口组织的高分辨图像,从而可以实时准确地监测伤口愈合状况。
本发明所述的柔性可拉伸的脑电极阵列采用高生物安全性的液态金属作为导电基质,并采用丝网印刷技术,制备出以聚二甲基硅氧烷(PDMS)为基底的高拉伸性和高生物安全性的脑电极阵列。与传统的金、银以及导电聚合物相比,液态金属不仅具有优异的拉伸性能,而且表现出很好的生物安全性。柔性脑电极阵列的具体工艺步骤如下:
(1)将液态金属加入到有机溶剂中,在超声或机械搅拌的作用下,液态金属被加工成微纳米颗粒。
(2)采用丝网印刷工艺,将液态金属导电油墨印刷成预先设计的脑电极阵列图案。
(3)待溶剂挥发完全后,在印刷的电极图案上面浇铸预固化的PDMS,进而固化完全后,便可得到柔性可拉伸的脑电极阵列。
本发明所述的光声成像***为商用的近红外光声成像***,主要包含脉冲激光器、超声波信号接收器以及数据处理分析模块,可以进行高分辨率和高对比度成像,同时对于伤口处的血管和血氧饱和度进行清晰的动态监测。
与现有技术相比,本发明可以具有但不限于以下有益效果:
(1)基于液态金属的柔性可拉伸脑电极阵列,具有高生物安全性的同时具有较低的弹性模量,可以紧密贴合在皮层伤口表面,检测出高分辨率的脑电信号。
(2)光声成像***不仅检测精度高,对组织无损伤,而且安全方便,是医学成像辅助诊断的重要进步。
(3)结合柔性脑电极阵列与光声成像***,克服了颅内伤口无法观察的难题,实现颅内伤口的无创监测,其监测准确度甚至可以满足临床监测指标要求。
附图说明
以下,结合附图来详细说明本发明的实施方案,其中:
图1示出了本发明采用的基于液态金属的柔性脑电极阵列示意图。
图2示出了大鼠海马细胞在液态金属电极上培养10天后的激光共聚焦显微镜观察的形貌图。
具体实施方式
下面通过具体的实施例进一步说明本发明,但是,应当理解为,这些实施例仅仅是用于更详细具体地说明之用,而不应理解为用于以任何形式限制本发明。
本部分对本发明试验中所使用到的材料以及试验方法进行一般性的描述。虽然为实现本发明目的所使用的许多材料和操作方法是本领域公知的,但是本发明仍然在此作尽可能详细描述。本领域技术人员清楚,在上下文中,如果未特别说明,本发明所用材料和操作方法是本领域公知的。
以下实施例中使用的试剂和仪器如下:
试剂:
铟镓合金购自Sigma Aldrich公司、正癸醇、PDMS(Sylgard 184)购自Dow Corning公司。
仪器:
超声波细胞破碎仪,购自必能信超声公司、型号S-450D;
光声成像***,购自加拿大VisualSonics公司、型号Vevo LAZR。
实施例1
本实施例用于说明本发明柔性脑电极阵列的加工制备方法,包括以下步骤:
将4克液态金属(铟镓合金,镓质量分数75.5%,铟质量分数24.5%)和1毫升正癸醇加入到5毫升离心管中。超声波细胞破碎仪在20%强度下超声2分钟,即可制备出液态金属微纳米颗粒,将制备的液态金属油墨加到丝网印刷模板上,印刷得到电极阵列的图案。接下来,将预固化的PDMS(PDMS:固化剂=10:1)浇铸到电极阵列图案上,将电极放到80摄氏度烘箱内固化2小时,待PDMS固化完全后,从基底上将PDMS揭下便可得到柔性脑电极阵列。将PDMS浇注在PET基底上,固化完全后,将PDMS从基底揭下,得到的电极阵列的基底是PDMS。
实施例2
本试验例用于说明柔性电极阵列结合光声成像***监测颅内伤口状况,包括以下步骤:
以大鼠为实验对象,对大鼠特定区域的脑组织伤口进行监测。大鼠麻醉后,在脑盖骨上制造一个2厘米×2厘米的开口,去掉硬脑膜后,表层彻底暴露,将实施例1制备的柔性电极贴合在大脑皮层上,柔性电极与商用EEG***连接,监测该区域的脑电信号变化。与此同时,利用光声成像***对监测部位进行实时准确成像,光声成像***探头对准脑组织的中间区域,电极阵列探测***的脑电信号,光声成像***对脑组织伤口进行实时成像。通过对比脑电信号与光声图像对脑组织的创伤情况进行判断。
尽管本发明已进行了一定程度的描述,明显地,在不脱离本发明的精神和范围的条件下,可进行各个条件的适当变化。可以理解,本发明不限于所述实施方案,而归于权利要求的范围,其包括所述每个因素的等同替换。
Claims (11)
1.一种颅内伤口愈合监测装置,其特征在于,所述装置包括:柔性电极阵列和光声成像***;通过将柔性电极阵列紧密贴合在脑组织伤口表面,检测出高分辨率的脑电信号,同时,光声成像***对脑组织伤口进行实时成像;通过对比脑电信号与光声图像对脑组织的创伤情况进行判断;
其中,所述柔性电极阵列包括:基底,和在所述基底上由液态金属颗粒汇聚而成的互联导线,并且,所述柔性电极阵列通过包括以下步骤的方法制备:
(1)将液态金属加入到有机溶剂中,将液态金属加工成微纳米颗粒,得到液态金属油墨;
(2)用步骤(1)制备的液态金属油墨绘制电极阵列图案,所述电极阵列图案的绘制方法为丝网印刷;
(3)待溶剂挥发完全后,在印刷的电极图案上面浇铸预固化的基底材料,固化完全后,得到柔性电极阵列。
2.根据权利要求1所述的装置,其特征在于,所述光声成像***为近红外光声成像***。
3.根据权利要求2所述的装置,其特征在于,所述光声成像***包含脉冲激光器、超声波信号接收器和数据处理分析模块。
4.根据权利要求1所述的装置,其特征在于,所述基底材料选自以下一种或多种:PDMS、Ecoflex、水溶性聚氨酯、聚乳酸、聚己内酯。
5.根据权利要求4所述的装置,其特征在于,所述基底材料为PDMS。
6.根据权利要求1所述的装置,其特征在于,所述液态金属选自以下一种或多种:铟镓合金、镓铟锡合金、铋锡合金。
7.根据权利要求6所述的装置,其特征在于,所述液态金属为铟镓合金。
8.根据权利要求1所述的装置,其特征在于,所述有机溶剂选自以下一种或多种:正癸醇、酒精、丙酮、N,N-二甲基甲酰胺、二氯甲烷、三氯甲烷、四氢呋喃。
9.根据权利要求8所述的装置,其特征在于,所述有机溶剂为正癸醇。
10.根据权利要求1所述的装置,其特征在于,步骤(1)中,所述加工为超声和/或机械搅拌。
11.权利要求1至10中任一项所述装置在制备用于监测伤口愈合的医疗产品中的应用。
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