Design of a miniature head-mounted fluorescence microscope based on gradient refractive index lenses
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摘要:
在对自由移动的动物进行脑神经实时观测时，微型头戴式荧光显微镜是当前最为前沿的脑科学观测仪器之一。但是，现今多数微型荧光显微镜的体积和重量受到严格限制，使得视场较小，无法同时观测多个脑区的神经活动，而少数视场大的产品重量较大，无法佩戴在小型动物身上。本研究使用轻量化、平面化和成像质量高的梯度折射率透镜进行大视场微型荧光显微镜设计，在保证大视场的前提下，减小了显微镜的重量。推导了倾斜光线入射梯度折射率透镜时的离轴像差公式，分析了梯度折射率透镜的折射率排布模型和像差校正情况。最终设计的微型荧光显微镜的视场为4 mm×4 mm，NA为0.1，样机重量仅为2.89 g，中心视场分辨率为13.9 μm，初步达到了自由移动小鼠的脑神经细胞分辨率。
Abstract:In real-time brain neural observation of freely moving animals, the miniature head-mounted fluorescence microscope is currently one of the most advanced brain science observation instruments. However, most existing miniature fluorescence microscopes, in order to meet strict size and weight constraints, have a limited field of view, making it impossible to simultaneously observe neural activity in multiple brain regions. On the other hand, a few products with a larger field of view are too heavy to be worn on small animals. This study employs lightweight, planar, and high-quality gradient refractive index lenses to reduce the microscope's weight while ensuring a large field of view. Using gradient refractive index lenses for the design of a large-field-of-view miniature fluorescence microscope, this research derives the off-axis aberration formula for oblique light incidence on gradient refractive index lenses, analyzes the refractive index distribution model and aberration correction of these lenses, and designs a miniature fluorescence microscope with a 4 mm×4 mm field of view, a numerical aperture (NA) of 0.1, and a prototype weight of only 2.89 g. The central visual field resolution is 13.9 μm, preliminarily achieving the resolution for neural cells in freely moving mice.
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图 1 倾斜光线经过梯度折射率透镜的模拟光路
Figure 1. Simulated optical path of oblique light rays through a gradient refractive index lens
图 6 显微镜的场曲和像散曲线
Figure 6. Field curvature and astigmatism curves of the miniature fluorescence microscope
图 11 畸变测试结果
Figure 11. Distortion test results of the miniature fluorescence microscope
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