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

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 mu m 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. (c) 2012 Elsevier B.V. All rights reserved.