The aim of this proposal is to create a transformative fluorescent microscopy system that is integrated with next generation mobile-phones for imaging single DNA molecules. This field-portable imaging interface running on a smartphone will have the sensitivity and contrast to image single molecule DNA fragments over a large field of view. Demonstrating DNA imaging on a state-of-the-art mobile-phone would serve as a stepping stone to next-generation mobile micro-analysis, sensing and diagnostic tools and could lead to single molecule DNA sequencing on a smartphone.
The proposed design will have the capability to be broadly used in various clinical applications including early detection of cancers (e.g. stomach and brain), nervous system disorders and drug resistance in infectious diseases. This cellphone based single molecule imaging, DNA platform could also assist health-care professionals, epidemiologists and policy makers to track emerging trends and shed more light on cause-effect relationships.
Intellectual Description: Single molecule imaging and DNA length quantification, both of which are currently not feasible using mobile-phone based imaging systems; require extreme detection sensitivity, signal-to-noise ratio (SNR), spatial resolution and automated sample handling and processing interfaces. To provide a transformative solution to these important tasks, the PI will design a multifunctional portable imaging device installed on a smartphone which will allow sample preparation and single molecule imaging within the same opto-mechanical attachment. This fluorescence microscope on a smartphone will be designed by integrating a laser diode, a disposable nano-channel chip, an external lens and a thin-film based emission filter in a robust attachment created by 3D printing techniques. High SNR fluorescence signal detection will be achieved by implementing high-angle/oblique illumination so that the direct excitation beam will not enter the low NA collection lens. They will also develop a compressive sampling based DNA length-estimation method which will utilize (i) the measured point spread function of the fluorescent microscope on the mobile-phone; (ii) the spatial sparsity of the objects (fluorescently labeled DNA molecules); and (iii) the linearity of the stretched DNA molecules within the field of view as a-priori constraints to estimate the length of the DNA fragment of interest with an accuracy that is significantly better than the resolution of their initial imaging system.
