Fluorescent magnetic bead and cell differentiation/counting using a CMOS SPAD matrix

Abstract

We present a monolithic silicon chip comprising a matrix of 84 single photon avalanche diodes (SPADs) to detect and discriminate fluorescent beads or fluorescently labeled single cells in a polydimethyl(-siloxane) (PDMS) cartridge that is positioned on top of the chip. Our detection is based on the different photon count when either a fluorescent or non-fluorescent bead or cell is present above a SPAD, due to the additional photons emitted from a fluorescent object. Our technique allows microscope-less fluorescence detection and permits easy exchange of the disposable microfluidic cartridge. We first demonstrate the working principle of our device by counting and discriminating fluorescent from non-fluorescent 3, 6 and 10 μm magnetic beads, which are commonly used as versatile mobile carriers for separating a target analyte from a matrix via magnetic forces in microfluidic lab-on-a-chip systems. We then apply our system to count and discriminate fluorescently-labeled MCF-7 breast cancer cells from unlabeled Jurkat cells mixed in a phosphate buffer saline (PBS) solution. Our device is robust and does not need complex microfluidic handling to achieve cell count without the need of external fluorescence detection bulky equipment.