Hyungsoon Ima,b,1, Cesar M. Castroa,c,1, Huilin Shaoa, Monty Lionga,2, Jun Songa,d, Divya Pathaniaa,b, Lioubov Fexona, Changwook Mina, Maria Avila-Wallacee, Omar Zurkiyaa,b, Junsung Rhoa, Brady Magaoaya, Rosemary H. Tambouretf, Misha Pivovarova,b, Ralph Weissledera,b,g,3, and Hakho Leea,b,3
aCenter for Systems Biology, Massachusetts General Hospital, Boston, MA 02114;
bDepartment of Radiology, Massachusetts General Hospital, Boston, MA 02114;
cMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114;
dSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
eDepartment of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114;
fDepartment of Pathology, Massachusetts General Hospital, Boston, MA 02114; and
gDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115
Abstract
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.
cancer diagnostics, smartphone, molecular sensing, point-of-care diagnostics, cervical cancer
1H.I. and C.M.C. contributed equally to this work.
2Present address: Cardno ChemRisk, San Francisco, CA 94105.
3To whom correspondence may be addressed.
Author contributions: R.W. and H.L. oversaw all research studies; H.I., C.M.C., R.W., and H.L. designed individual projects; C.M.C., M.A.-W., O.Z., and R.W. designed clinical studies and obtained samples; H.I., H.S., J.S., D.P., C.M., O.Z., J.R., and B.M. performed research; C.M.C., H.S., M.L., D.P., and J.R. contributed new reagents/analytic tools; H.I., C.M.C., H.S., M.L., J.S., D.P., L.F., C.M., M.A.-W., O.Z., J.R., B.M., R.H.T., M.P., R.W., and H.L. analyzed data; and H.I., C.M.C., R.W., and H.L. wrote the paper.