한빛사논문
Chen-Han Huang,†,‡ Yong Il Park,†,§ Hsing-Ying Lin,† Divya Pathania,† Ki Soo Park,† Maria Avila-Wallace,⊥ Cesar M. Castro,†,# Ralph Weissleder,*,†,∇ and Hakho Lee*,†
† Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States
‡ Department of Biomedical Sciences and Engineering, National Central University, No. 300, Zhongda Rd., Zhongli District, Taoyuan City 32001, Taiwan
§ School of Chemical Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea
⊥ Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States
# Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States
∇ Department of Systems Biology, Harvard Medical School, 200 Longwood Ave., Boston, Massachusetts 02115, United States
*Corresponding Authors
C.-H.H., Y.I.P., and H.-Y.L. contributed equally to this work.
Abstract
We report a sensitive and versatile biosensing approach, LUCID (luminescence compact in vitro diagnostics), for quantitative molecular and cellular analyses. LUCID uses upconversion nanoparticles (UCNPs) as luminescent reporters in mutually exclusive photoexcitation and read-out sequences implemented on a smartphone. The strategy improves imaging signal-to-noise ratios, eliminating interference from excitation sources and minimizing autofluorescence, and thus enables filterless imaging. Here we developed a miniaturized detection system and optimized UCNPs for the system and biological applications. Nanoparticle luminescence lifetime was extended by controlling particle structure and composition. When tested with a range of biological targets, LUCID achieved high detection sensitivity (0.5 pM for protein and 0.1 pM for nucleic acids), differentiated bacterial samples, and allowed profiling of cells. In proof-of-concept clinical use, LUCID demonstrated effective screening of cancer cells in cervical brushing specimens, identifying patients at high risk for malignancy. These results suggest that LUCID could serve as a broadly applicable and inexpensive diagnostic platform.
KEYWORDS : diagnostic, point-of-care, nanoparticles, luminescence, global health
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