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

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

Abstract

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.

Keywords: biosensors; digital assay; platinum nanoparticles; protein detection; smartphone.

Publication types

  • Review

MeSH terms

  • Biological Assay / methods*
  • Biomarkers / chemistry*
  • Biosensing Techniques / methods*
  • Humans
  • Point-of-Care Systems
  • Proteins / chemistry*
  • Smartphone / instrumentation*

Substances

  • Biomarkers
  • Proteins