A graphene-based chemical nose/tongue approach for the identification of normal, cancerous and circulating tumor cells

Li Wu,Xiaogang Qu,Haiwei Ji,Xiang Ran,Yijia Guan,Jinsong Ren

doi:10.1038/am.2017.11

Abstract

The development of reliable, cost-effective, and sensitive detection and monitoring assays is particularly important for the early diagnosis and treatment of cancer. Here, we report an array-based system for cell sensing using a ‘chemical nose/tongue’ approach that exploits subtle changes in the physicochemical nature of different cell surfaces. A family of synthetic and biomolecular functionalized graphene elements was used to develop the sensing array. Their different interactions with dissimilar cell surfaces were transduced to an ultrasensitive electrochemical impedance signal, providing a fingerprint for the classification and identification of different cells. This electrochemical array sensing platform has ultrahigh sensitivity that can detect a single-cell type from one cell. Furthermore, it can discern different cell types at levels as low as 100 cells with high accuracy for (i) different cell types; (ii) cancerous, multidrug-resistant cancerous and metastatic human breast cells; and (iii) artificial circulating tumor cells (CTCs). The graphene-based electrochemical sensing platform presented here can more generally be applied to array sensor fabrication and can provide highly efficient signal transduction pathways to improve the detection response of each recognition element.

Highlights

Cancer continues to be a major cause of mortality despite decades of treatment effort and expense
Cancer cell detection mainly focuses on the identification of cellular signatures because cancerous cells are differentiated from noncancerous cells on the basis of intracellular or extracellular biomarkers.[3]
EpCAM is not expressed in some types of cancer cells, and whether the EpCAM-positive circulating tumor cells (CTCs) may or may not have any metastatic potential has been the subject of debate

Summary

Introduction

Cancer continues to be a major cause of mortality despite decades of treatment effort and expense. Various promising detection methods involving the specific recognition of biomarkers on the cell surface (for example, overexpressed antigens) or intracellular biomarkers (for example, dysregulation of RNA/proteins inside the cell) have been developed, such as PCR,[4] enzyme-linked immunosorbent assay,[5] surface plasmon resonance,[6] microcantilevers[7] and bioimaging.[8] the design and preparation of the specific ligand-based sensors are generally costly and time-consuming. These methods all require previous knowledge of specific biomarkers. There is an urgent need to develop an efficient platform for cancer cell analysis, especially for CTCs.[11,12] When this technology becomes clinically available, a blood sample may be used as a liquid biopsy in tumor diagnostics, which is accessible for both the patient and physician

Methods

Results

Conclusion