Toward the detection of single virus particle in serum

There is a grand challenge for the detection of target molecules at single molecule sensitivity in a bulk body fluid for the early diagnosis of diseases. We report our progress on tackling this challenge via the combination of fluorescence cross-correlation spectroscopy (FCCS) and micro fabricated devices toward highly sensitive detection of the dengue virus. We demonstrate that by using a dengue-specific antibody, we can probe the individual dengue virus in a nanomolar bulk solution by following the specific association of dengue antibody using FCCS. Consequently, we designed and fabricated a microfluidic chamber array structure and were able to compartmentalize the bulk aqueous dengue sample into femtoliter volumes using such a device. More importantly we demonstrate that we can differentiate between the compartments containing the dengue virus and the virus-free compartments. Our experiment suggests that by expanding the throughput using microfluidic devices integrated with FCCS, both of which can be achieved practically, we should be able to detect single virus particle in human body fluids in the near future.