Converging Multidimensional Sensor and Machine Learning Toward High-Throughput and Biorecognition Element-Free Multidetermination of Extracellular Vesicle Biomarkers.

Journal: ACS sensors
PMID:

Abstract

Extracellular vesicles (EVs) are a frontier class of circulating biomarkers for the diagnosis and prognosis of different diseases. These lipid structures afford various biomarkers such as the concentrations of the EVs () themselves and carried proteins (). However, simple, high-throughput, and accurate determination of these targets remains a key challenge. Herein, we address the simultaneous monitoring of and from a single impedance spectrum without using recognizing elements by combining a multidimensional sensor and machine learning models. This multidetermination is essential for diagnostic accuracy because of the heterogeneous composition of EVs and their molecular cargoes both within the tumor itself and among patients. Pencil HB cores acting as electric double-layer capacitors were integrated into a scalable microfluidic device, whereas supervised models provided accurate predictions, even from a small number of training samples. User-friendly measurements were performed with sample-to-answer data processing on a smartphone. This new platform further showed the highest throughput when compared with the techniques described in the literature to quantify EVs biomarkers. Our results shed light on a method with the ability to determine multiple EVs biomarkers in a simple and fast way, providing a promising platform to translate biofluid-based diagnostics into clinical workflows.

Authors

  • Caroline Y N Nicoliche
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
  • Ricardo A G de Oliveira
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
  • Giulia S da Silva
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
  • Larissa F Ferreira
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
  • Ian L Rodrigues
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
  • Ronaldo C Faria
    Department of Chemistry, Federal University of São Carlos, São Carlos, São Paulo 13565-905, Brazil.
  • Adalberto Fazzio
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
  • Emanuel Carrilho
    São Carlos Institute of Chemistry, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil.
  • Letícia G de Pontes
    São Carlos Institute of Chemistry, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil.
  • Gabriel R Schleder
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.
  • Renato S Lima
    Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil.