On-chip biofluorescence imaging inside a brain tissue phantom using a CMOS image sensor for in vivo brain imaging verification

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 μM is possible. The 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 μm. The fully packaged chip, specially designed with this technique is about 350 μm thick and 2.7 mm wide. The image sensor pixel size of 7.5 μm × 7.5 μm 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.