Abrantes Mafalda, Pereira Tiago, Silva Patrícia, Falcão Margarida, Borme Jérôme, Alpuim Pedro, Jacinto Luis
Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine, University of Porto (FMUP), Porto, 4200-319, Portugal.
International Iberian Nanotechnology Laboratory, Braga, 4715-330, Portugal.
Biomed Microdevices. 2025 May 29;27(2):24. doi: 10.1007/s10544-025-00754-1.
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 mm but can output up to 2.5 mW of optical power with an irradiance of 175 mW/mm. 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.
The online version contains supplementary material available at 10.1007/s10544-025-00754-1.
光遗传学是一种广泛用于通过光刺激剖析神经回路的工具，但它要求将光传递到大脑内部的光敏神经元。带有微尺度发光二极管（µLED）的可植入神经探针是一种新兴的向大脑传递光的方法，具有卓越的光输出控制能力。然而，将µLED集成到神经探针中的方法依赖于复杂的制造工艺。在此，我们开发了一种可植入的小型神经探针，它仅使用硅中的标准光刻工艺以及在贴片机上使用定制3D打印工具的定制自动化LED安装方法，集成了高效的商用倒装芯片µLED。该探针的横截面积小于0.013平方毫米，但能够输出高达2.5毫瓦的光功率，辐照度为175毫瓦/平方毫米。由于LED的高插入效率，该神经探针能够在不超过估计热点温度升高1摄氏度以上的情况下，执行高达20赫兹和80%占空比的刺激方案。这些神经探针在体内得到了验证，转基因小鼠运动皮层的脑活动被探针发出的脉冲光可靠地调制。
在线版本包含可在10.1007/s10544-025-00754-1获取的补充材料。
