High-Throughput, Living Single-Cell, Multiple Secreted Biomarker Profiling Using Microfluidic Chip and Machine Learning for Tumor Cell Classification

Adv Healthc Mater. 2022 Jul;11(13):e2102800. doi: 10.1002/adhm.202102800. Epub 2022 May 4.

Abstract

Secreted proteins provide abundant functional information on living cells and can be used as important tumor diagnostic markers, of which profiling at the single-cell level is helpful for accurate tumor cell classification. Currently, achieving living single-cell multi-index, high-sensitivity, and quantitative secretion biomarker profiling remains a great challenge. Here, a high-throughput living single-cell multi-index secreted biomarker profiling platform is proposed, combined with machine learning, to achieve accurate tumor cell classification. A single-cell culture microfluidic chip with self-assembled graphene oxide quantum dots (GOQDs) enables high-activity single-cell culture, ensuring normal secretion of biomarkers and high-throughput single-cell separation, providing sufficient statistical data for machine learning. At the same time, the antibody barcode chip with self-assembled GOQDs performs multi-index, highly sensitive, and quantitative detection of secreted biomarkers, in which each cell culture chamber covers a whole barcode array. Importantly, by combining the K-means strategy with machine learning, thousands of single tumor cell secretion data are analyzed, enabling tumor cell classification with a recognition accuracy of 95.0%. In addition, further profiling of the grouping results reveals the unique secretion characteristics of subgroups. This work provides an intelligent platform for high-throughput living single-cell multiple secretion biomarker profiling, which has broad implications for cancer investigation and biomedical research.

Keywords: cell classification; graphene oxide quantum dots; microfluidic chips; secreted biomarkers; single cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cell Separation
  • Humans
  • Machine Learning
  • Microfluidics* / methods
  • Neoplasms* / diagnosis

Substances

  • Biomarkers, Tumor