Small form factor implantable neural probe with efficient flip chip µLED for in vivo optogenetics

IF 3.3 4区医学 Q3 ENGINEERING, BIOMEDICAL

Biomedical Microdevices Pub Date : 2025-05-29 DOI:10.1007/s10544-025-00754-1

Mafalda Abrantes, Tiago Pereira, Patrícia Silva, Margarida Falcão, Jérôme Borme, Pedro Alpuim, Luis Jacinto

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引用次数: 0

Abstract

Optogenetics is a widely used tool to dissect neural circuits with optical stimulation, but it requires that light is delivered to photosensitive neurons inside the brain. Implantable neural probes with microscale LEDs (µLEDs) are an emerging approach to delivering light to the brain with superior light output control. However, approaches to integrate µLEDs in neural probes depend on complex fabrication processes. Here, we developed an implantable small form factor neural probe that integrates highly efficient commercial flip chip µLEDs using only standard lithography processes in silicon and a custom automated LED mounting approach with custom 3D-printed tools on a pick-and-place machine. The probe has a cross-sectional area under 0.013 mm² but can output up to 2.5 mW of optical power with an irradiance of 175 mW/mm². Due to the high plug efficiency of the LED, the neural probe can perform stimulation protocols up to 20 Hz and 80% duty cycles without surpassing estimated hotspot temperature elevations above 1 ºC. The neural probes were validated in vivo, with brain activity in the motor cortex of transgenic mice being reliably modulated by pulsed light emitted from the probe.

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小型植入式神经探针，高效倒装芯片，用于体内光遗传学。

光遗传学是一种广泛使用的工具，可以通过光刺激来解剖神经回路，但它需要将光传递到大脑内的光敏神经元。带有微型led（µLEDs）的植入式神经探针是一种新兴的向大脑传递光的方法，具有优越的光输出控制。然而，将微led集成到神经探针中的方法依赖于复杂的制造工艺。在这里，我们开发了一种可植入的小尺寸神经探针，它集成了高效的商业倒装芯片µLED，仅使用标准的硅光刻工艺和定制的自动化LED安装方法，并在拾取和放置机器上使用定制的3d打印工具。该探头的截面积小于0.013 mm2，但可以输出高达2.5 mW的光功率，辐照度为175 mW/mm2。由于LED的高插头效率，神经探针可以执行高达20 Hz和80%占空比的刺激协议，而不会超过估计的热点温度高于1ºC。神经探针在体内得到了验证，转基因小鼠运动皮层的大脑活动被探针发出的脉冲光可靠地调节。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedical Microdevices 工程技术-工程：生物医学

CiteScore

6.90

自引率

3.60%

发文量

审稿时长

6 months

期刊介绍： Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.