Fully Integrated Time-Gated 3D Fluorescence Imager for Deep Neural Imaging
Jaebin Choi, Adriaan J. Taal, William Meng, Eric H. Pollmann, John W. Stanton, Changhyuk Lee, Sajjad Moazeni, Laurent Moreaux, M. L. Roukes, Kenneth L. Shepard
Abstract
This paper presents a device for time-gated fluorescence imaging in the deep brain, consisting of two on-chip laser diodes and 512 single-photon avalanche diodes (SPADs). The edge-emitting laser diodes deliver fluorescence excitation above the SPAD array, parallel to the imager. In the time domain, laser diode illumination is pulsed and the SPAD is time-gated, allowing a fluorescence excitation rejection up to O.D. 3 at 1 ns of time-gate delay. Each SPAD pixel is masked with Talbot gratings to enable the mapping of 2D array photon counts into a 3D image. The 3D image achieves a resolution of 40, 35, and 73 μm in the x, y, and z directions, respectively, in a noiseless environment, with a maximum frame rate of 50 kilo-frames-per-second. We present measurement results of the spatial and temporal profiles of the dual-pulsed laser diode illumination and of the photon detection characteristics of the SPAD array. Finally, we show the imager's ability to resolve a glass micropipette filled with red fluorescent microspheres. The system's 420 μm-wide cross section allows it to be inserted at arbitrary depths of the brain while achieving a field of view four times larger than fiber endoscopes of equal diameter.