Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts. Significance Smartphones and wearable electronics have advanced tremendously over the last several years but fall short of allowing their use for molecular diagnostics. We herein report a generic approach to enable molecular diagnostics on smartphones. The method utilizes molecular-specific microbeads to generate unique diffraction patterns of “blurry beads” which can be recorded and deconvoluted by digital processing. We applied the system to resolve individual precancerous and cancerous cells as well as to detect cancer-associated DNA targets. Because the system is compact, easy to operate, and readily integrated with the standard, portable smartphone, this approach could enable medical diagnostics in geographically and/or socioeconomically limited settings with pathology bottlenecks.