Color-Filtered Si Photodiode Array for On-Chip Calcium Imaging in Living Cells

Abstract

Intracellular calcium dynamics is crucial in understanding cell activities [1]. To monitor the change in intracellular calcium concentration ([Ca2+]), fluorescent imaging has been broadly used for its outstanding sensitivity and specificity [2]. This method delivers fluorescent molecules into living cells. These molecules specifically respond to the binding of Ca2+ ions, followed by a change in their fluorescence intensity. To date, most Ca2+ imaging is conducted by fluorescent microscopes that have high spatiotemporal resolutions. However, these microscopes are usually large in size, and have limited access to cells deep in the tissue [3]. For these reasons, on-chip fluorescent imaging systems have recently emerged as a viable alternative for their miniaturized and implantable nature that can grant deep tissue imaging [4]. In this work, we present an on-chip calcium imaging platform based on a $20-\mu\mathrm{m}$ pitched passive Si photodiode (PD) array assembled with a high-performance color filter. We chose a passive Si PD array structure for their CMOS compatibility and low-power operation (sub- $10 \mu\mathrm{W}$ power, $\sim 0.2 \mathrm{mW}/\mathrm{mm}^{2}$ power density), which allows chronic deep tissue imaging. Importantly, we coated a light absorber layer on top of the PD array to serve as a color filter, which offers $\mathrm{a} > 10^{2}$ extinction ratio to reject the excitation light provided by the microscope. The emission light (peaked at ~602 nm) from the calcium indicators in C2C12 cells passes the filter with a > 76% transmission coefficient. The Ca2+ imaging data of our PD array well match with those of a fluorescent microscope. Our results show that calcium ionophores induce heterogeneous intracellular [Ca2+] dynamics in different cells. This work suggests the possible use of the PD array towards an on-chip live-cell imaging system with deep tissue access.