Microelectromechanical System-Based Sensing Arrays for Comparative in Vitro Nanotoxicity Assessment at Single Cell and Small Cell-Population Using Electrochemical Impedance Spectroscopy

ACS Appl Mater Interfaces. 2016 Mar 9;8(9):5804-12. doi: 10.1021/acsami.5b11409. Epub 2016 Feb 26.


The traditional in vitro nanotoxicity assessment approaches are conducted on a monolayer of cell culture. However, to study a cell response without interference from the neighbor cells, a single cell study is necessary; especially in cases of neuronal, cancerous, and stem cells, wherein an individual cell's fate is often not explained by the whole cell population. Nonetheless, a single cell does not mimic the actual in vivo environment and lacks important information regarding cell communication with its microenvironment. Both a single cell and a cell population provide important and complementary information about cells' behaviors. In this research, we explored nanotoxicity assessment on a single cell and a small cell population using electrochemical impedance spectroscopy and a microelectromechanical system (MEMS) device. We demonstrated a controlled capture of PC12 cells in different-sized microwells (to capture a different number of cells) using a combined method of surface functionalization and dielectrophoresis. The present approach provides a rapid nanotoxicity response as compared to other conventional approaches. This is the first study, to our knowledge, which demonstrates a comparative response of a single cell and small cell colonies on the same MEMS platform, when exposed to metaloxide nanoparticles. We demonstrated that the microenvironment of a cell is also accountable for cells' behaviors and their responses to nanomaterials. The results of this experimental study open up a new hypothesis to be tested for identifying the role of cell communication in spreading toxicity in a cell population.

Keywords: MEMS; cell-communication; impedance spectroscopy; nanotoxicity; single cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Copper / chemistry
  • Dielectric Spectroscopy*
  • Electrodes
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity
  • Micro-Electrical-Mechanical Systems
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • PC12 Cells
  • Rats
  • Tin Compounds / chemistry
  • Titanium / chemistry
  • Toxicity Tests


  • Tin Compounds
  • titanium dioxide
  • indium tin oxide
  • Copper
  • Titanium
  • cupric oxide