On-chip biofluorescence imaging inside a brain tissue phantom using a CMOS image sensor for in vivo brain imaging verification
On-chip biofluorescence imaging inside a brain tissue phantom using a CMOS image sensor for in vivo brain imaging verification
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DOI：
10.1016/j.snb.2005.12.020
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发表时间：
2006-11-24
影响因子：
8.4
通讯作者：
Ohta, Jun
中科院分区：
文献类型：
--
作者：
Ng, David C.;Tokuda, Takashi;Ohta, Jun
我们已经开发了一个芯片上的生物荧光成像设备，通过封装一个专用的CMOS图像传感器，使用一个简单的技术。通过使用片上成像配置，我们已经验证了体内荧光成像内的一个专门开发的脑组织幻影，非常类似于哺乳动物的大脑。为了实现片上成像，将激发光滤波器应用到芯片上。通过过滤器的多个涂层实现了-44dB的透射率。AMC荧光团的芯片上测量显示，1 μ M的浓度的检测是可能的。新的体模介质具有类似于小鼠大脑的机械刚度和光学特性。证明了在体模样品内对释放的荧光团成像的可行性。它示出，光散射在幻影介质中不显着降低图像分辨率，如果成像深度保持低于500 μ m。用这种技术专门设计的完全封装的芯片约350 μ m厚，2.7 mm宽。7.5 μ m × 7.5 μ m的图像传感器像素大小接近单个神经元细胞的大小。虽然该装置是专门设计用于在体内成像的小鼠海马体，研究其神经元的活动，广泛的应用被预见在生物医学和制药领域。(c)2005 Elsevier B. V.保留所有权利。
We have developed an on-chip biofluorescence imaging device by packaging a dedicated CMOS image sensor using a simple technique. By using on-chip imaging configuration, we have verified in vivo fluorescence imaging inside a specially developed brain tissue phantom that closely resembles the mammalian brain. In order to implement on-chip imaging, an excitation light filter is applied onto the chip. A transmittance of -44 dB is achieved by multiple coating of the filter. On-chip measurement of the AMC fluorophore shows that detection of concentration of 1 mu M is possible. ne phantom medium has mechanical rigidity and optical property similar to the mouse brain. Feasibility of imaging the released fluorophore inside the phantom sample is demonstrated. It is shown that light scattering in the phantom medium does not reduce the image resolution considerably, if the imaging depth is kept below 500 mu m. The fully packaged chip, specially designed with this technique is about 350 mu m thick and 2.7 mm wide. The image sensor pixel size of 7.5 mu m x 7.5 mu m is close to the size of a single neuron cell. Although the device is designed specially for in vivo imaging of the mouse hippocampus to study its neuronal activity, a wide range of applications are foreseen in the biomedical and pharmaceutical field. (c) 2005 Elsevier B.V. All rights reserved.