A novel flip-chipped integrated single photon detection platform for proteomics

Novel integrated sensors will be required for future detection platforms for the measurement of fluorescence and luminescence. The current trend towards integration of optical detectors and the broad advances in optical emitting dyes and proteins will be combined in robust, low-cost, point-of-use, diagnostic equipment. To this end we are experimenting with an integrated optical hybrid sensing device which will combine a flip-chipped, array of solid-state single photon counting detectors with surface mount passive quench circuits on a conventional glass substrate. This flip-chipped arrangement both 1) increases the speed of response of the detector and 2) increases the robustness and ease of integration and reduces single photon detector handling requirements. The potential of integrated solid-state photon detectors will be demonstrated for the real-time quantitative detection of luciferase, a light emitting protein expression reporter molecule. A 15μm solid-state Geiger-mode avalanche photodiode (APD) operating in single photon counting mode will be compared with a standard photomultiplier tube (PMT) for luciferase luminescence detection. Detection levels of 2×10⁶ and 1×10⁷ enzyme molecules will be demonstrated for PMT and Geiger-mode APD respectively. The size of the Geiger-mode APD active area will be shown to be the limiting factor in luciferase signal detection for non-integrated applications. A simple geometric model will show that detection limits of 1×10⁴ are achievable in integrated sensing platforms using room temperature operated single photon counting detectors.