Spheroid-3D and Monolayer-2D Intestinal Electrochemical Biosensor for Toxicity/Viability Testing: Applications in Drug Screening, Food Safety, and Environmental Pollutant Analysis

Evangelia Flampouri, Shahzad Imar, Kieran Oconnell, Baljit Singh

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

The rise of three-dimensional cell culture systems that provide in vivo-like environments for pharmaco-toxicological models has prompted the need for simple and robust viability assays suitable for complex cell architectural structures. This study addresses that challenge with the development of an in vitro enzyme based electrochemical sensor for viability/cytotoxicity assessment of two-dimensional (2D) monolayer and three-dimensional (3D) spheroid culture formats. The biosensor measures the cell viability/toxicity via electrochemical monitoring of the enzymatic activity of nonspecific esterases of viable cells, through the hydrolysis of 1-naphthyl acetate to 1-naphthol. The proposed sensor demonstrated strong correlation (r = 0.979) with viable cell numbers. Furthermore, the model intestinal toxicants diclofenac (DFC, pharmaceutical), okadaic acid (OA, food-safety), and mancozeb (MZB, environmental) were used for the functional evaluation of the proposed sensor using 2D and 3D culture formats. Sensor performance showed high consistency with conventional cell viability/cytotoxicity assays (MTT/CFDA-AM) for all toxicants, with the sensor IC 50 values matching the relevant viability LC 50 values at the 95% confidence interval range for 2D (DCF: 1.19-1.26 mM, MZB: 10.28-14.18 μM, OA: 40.91-77.13 nM) and 3D culture formats (DCF: 1.02-4.78 mM, MZB: 11.26-15.16 μM, OA: 162.09-179.67 nM). The presented results demonstrate the feasibility of the proposed sensor as a robust endpoint screening tool for both 2D and 3D cytotoxicity assessment.

Original languageEnglish
Pages (from-to)660-669
Number of pages10
JournalACS Sensors
Volume4
Issue number3
DOIs
Publication statusPublished - 22 Mar 2019

Keywords

  • cytotoxicity
  • screen-printed electrode
  • spheroid-3D, electrochemical biosensor
  • substrate and enzymatic product
  • viability, nonspecific esterase

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