Optically-Gated Self-Calibrating Nanosensors: Monitoring
pH and Metabolic Activity of Living Cells
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Abstract
Quantitative
detection of biological and chemical species is critical to numerous
areas of medical and life sciences. In this context, information regarding
pH is of central importance in multiple areas, from chemical analysis,
through biomedical basic studies and medicine, to industry. Therefore,
a continuous interest exists in developing new, rapid, miniature,
biocompatible and highly sensitive pH sensors for minute fluid volumes.
Here, we present a new paradigm in the development of optoelectrical
sensing nanodevices with built-in self-calibrating capabilities. The
proposed electrical devices, modified with a photoactive switchable
molecular recognition layer, can be optically switched between two
chemically different states, each having different chemical binding
constants and as a consequence affecting the device surface potential
at different extents, thus allowing the ratiometric internal calibration
of the sensing event. At each point in time, the ratio of the electrical
signals measured in the ground and excited states, respectively, allows
for the absolute concentration measurement of the molecular species
under interest, without the need for electrical calibration of individual
devices. Furthermore, we applied these devices for the real-time monitoring
of cellular metabolic activity, extra- and intracellularly, as a potential
future tool for the performance of basic cell biology studies and
high-throughput personalized medicine-oriented research, involving
single cells and tissues. This new concept can be readily expanded
to the sensing of additional chemical and biological species by the
use of additional photoactive switchable receptors. Moreover, this
newly demonstrated coupling between surface-confined photoactive molecular
species and nanosensing devices could be utilized in the near future
in the development of devices of higher complexity for both the simultaneous
control and monitoring of chemical and biological processes with nanoscale
resolution control