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Angew Chem Int Ed Engl. 2019 Sep 23;58(39):13922-13928. doi: 10.1002/anie.201906856. Epub 2019 Aug 21.

Quantitation of Femtomolar-Level Protein Biomarkers Using a Simple Microbubbling Digital Assay and Bright-Field Smartphone Imaging.

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Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Computer and Information Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.


Quantitating ultra-low concentrations of protein biomarkers is critical for early disease diagnosis and treatment. However, most current point-of-care (POC) assays are limited in sensitivity. Herein, we introduce an ultra-sensitive and facile microbubbling assay for the quantification of protein biomarkers with a digital-readout method that requires only a smartphone camera. We used machine learning to develop a smartphone application for automated image analysis to facilitate accurate and robust counting. Using this method, post-prostatectomy surveillance of prostate specific antigen (PSA) can be achieved with a detection limit (LOD) of 2.1 fm (0.060 pg mL-1 ), and early pregnancy detection using βhCG can be achieved with a of 0.034 mIU mL-1 (2.84 pg mL-1 ). This work provides the proof-of-principle of the microbubbling assay with a digital readout as an ultra-sensitive technology with minimal requirement for power and accessories, facilitating future POC applications.


biosensors; digital assay; platinum nanoparticles; protein detection; smartphone


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