Biomedical Engineering Reference
In-Depth Information
of ions or biomolecules at the gate insulator electrostatically interact with electrons
in silicon crystal across the thin gate insulator resulting in the threshold voltage
change. Particularly, we are interested in ion transportations through membrane
proteins such as ion channels and ion pumps at cell membrane and trying to
detect ionic behaviors based on biological phenomena using a cell-coupled gate
semiconductor. The semiconductor-based biosensing devices have good advantages
of label-free, real-time, and noninvasive method, and we can make an arrayed device
for a multitarget analysis by use of the conventional semiconductor processes.
In the point of detection of cell functions, we propose the device structure
with three components such as target, signal transduction interface, and detection
device. Since we utilize the cell-coupled gate semiconductor, we are trying to design
the signal transduction interface in order to detect ion charges specifically and
selectively based on each cell function.
For example, in order to detect drug effect on cancer cells, we need to detect
ion charges based on programmed cell death “apoptosis” using the cell-coupled
gate semiconductor and develop the signal transduction interface to trap them. The
previous work showed the possibility of potassium ions, chloride ions, and water
release in the early stage of apoptosis. Therefore, we have focused on potassium ion
release based on apoptosis and succeeded in the real-time, direct, and noninvasive
monitoring of their flow. In particular, this result was accomplished by use of crown
ether monolayer to trap selectively potassium ion as signal transduction interface
of the cell-coupled gate semiconductor. Moreover, we have found the possibility of
multitarget detection for high-throughput screening of drug effect using the cell-
coupled gate semiconductor with some transfected cancer cells in our study.
Using the cell-coupled gate semiconductor, furthermore, we have found the
possibilities of a real-time and noninvasive monitoring of various cell functions,
as follows:
•
Interaction between substrate and transporter at cell membrane for drug effect
detection
•
Embryo activity based on in vitro fertilization (IVF) for assisted reproductive
technology (ART)
•
Glucose response of pancreatic “-cells for insulin secretion
•
Differentiation of stem cells such as murine or human iPS cells
•
Autophagy for accommodation to starvation
•
Expression of sialic acid at cell membrane of cancer cells
•
Cell motility at biomaterials
•
Other cell function
Acknowledgements
The authors wish to thank Professor K. Kataoka of the University of Tokyo
in Japan and Professor Y. Miyahara of the National Institute for Materials Science (NIMS)
in Japan for their help and useful discussion. These works were partly supported by Center
for NanoBio Integration (CNBI), Sentan-Keisoku, and CREST projects, Japan Science and
Technology Agency (JST).
