Biosensors and Bioelectronics 26 (2011) 3371–3375
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Biosensors and Bioelectronics
journal homepage: www.elsevier.com/locate/bios
Short communication
Electrochemical cell-based chip for the detection of toxic effects of bisphenol-A
on neuroblastoma cells
Md. Abdul Kafi
a
, Tae-Hyung Kim
b
, Jeung Hee An
b
, Jeong-Woo Choi
a,b,∗
a
Interdisciplinary Program of Integrated Biotechnology, Sogang University, #1 Shinsu-Dong, Mapo-Gu, Seoul 121-742, Republic of Korea
b
Department of Chemical & Biomolecular Engineering, Sogang University, #1 Shinsu-Dong, Mapo-Gu, Seoul 121-742, Republic of Korea
article info
Article history:
Received 27 October 2010
Received in revised form 2 December 2010
Accepted 16 December 2010
Available online 23 December 2010
Keywords:
Bisphenol-A
Cyclic voltammetry
MTT assay
SH-SY5Y cells
Nanobiochip
abstract
A cell-based chip was fabricated for the electrochemical detection of the dose-dependent effects of
bisphenol-A (BPA) on neuroblastoma cells (SH-SY5Y), which showed dual-mode correlation as a standard
curve. Toxicity assessment of BPA became very important in environmental toxicants detection since BPA
can be reached out easily from various common plastic-based product and give negative cellular effects
on living organism. Cell chip was fabricated by immobilizing cells on C(RGD)
4
peptide coated electrode
to detect the cytotoxicity of BPA electrochemically. Redox properties in living cells were determined by
cyclic voltammetry using a home-made three-electrode system, and the cathodic peak current (I
pc
) was
used as a parameter for measurement of the effect of BPA on cell viability. The peak current, I
pc
value
increased with the concentration of BPA up to 300 nM and then decreased because of the stimulation of
cancer cell activity at the concentration of BPA below 300 nM and cytotoxicity at the concentration of BPA
above 300 nM, respectively. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay
and optical microscopy-based morphological analysis confirmed the results of electrochemical study.
This dual-mode correlation between the concentration of BPA and voltammetric signal intensity should
be firstly considered to analyze its dose-dependent stimulus and cytotoxic effects on neuroblastoma cells
by cell chip.
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
Bisphenol A (BPA) is a common monomer used in the manufac-
ture products such as a polycarbonate plastic food storage container
and dental sealants. BPA itself has been produced in the amount
of 6.4 billion pounds per year (vom Saal and Hughes, 2005), and
is also leached out from polycarbonate plastic products (Krishnan
et al., 1993; Welshons et al., 2003). The leaching-out rate of BPA
from polycarbonate tends to increase in older plastic products due
to severe exposure to the environment (Howdeshell and Peterman,
2003). The half-life of BPA has been reported to be less than 2 days
in river water (Zalko et al., 2003). However, due to its negative cel-
lular effects on living organisms, BPA dissolved in drinking water
should still be monitored (Keri et al., 2007; Vandenberg et al., 2007).
Several methods have been tried to determine the effects of BPA
on cells including ELISA (Le et al., 2008), neutral red uptake assay
(McGlinchey, 2009), MMT assay (Gursory et al., 2001), and protein
analysis (Lee et al., 2004). All the above mentioned studies using the
∗
Corresponding author at: Department of Chemical and Biomolecular Engineer-
ing, Sogang University, Seoul, Republic of Korea. Tel.: +82 2 705 8480;
fax: +82 2 3273 0331.
E-mail address: jwchoi@sogang.ac.kr (J.-W. Choi).
conventional methods successfully detected the effect of BPA up
to micromolar concentration; however, did not focus on nanomo-
lar concentration regarding to cytotoxicity due to the limitation
of detection range. Furthermore, these methods are laborious and
time consuming.
The cell-based sensor array has been developed as a possible
candidate due to its high sensitivity, wide application potentialities
and ease of use compared to conventional optical and fluorescence
techniques. Since a cell has its own redox properties and toxicants
can be monitored electrochemically (Li et al., 2005), the electro-
chemical methods such as cyclic voltammetry (Xu et al., 2000) and
amperometry have been tried to detect toxicants in solution quan-
titatively by analyzing the signal changes from cells immobilized
on an electrode in different concentrations of toxicants (Yeon and
Park, 2005). Recently, we have introduced a cell chip which can
detect environmental toxins (Choi et al., 2007) and the effects of
drugs on cells (El-Said et al., 2009a,b) electrochemically. Using our
cell chip technology, we successfully found the negative correla-
tion between electrochemical voltammetric signal intensity from
cells and the concentration of toxicants (El-Said et al., 2009a,b).
Effects of BPA on neural cancer cells (PC12) were also determined
in our previous study (Choi et al., 2010); however, in the previous
report, indium tin oxide (ITO) film was used as a working elec-
trode to integrate Raman technique that sacrificed the sensitivity of
0956-5663/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.bios.2010.12.030