Nanogap based label-free impedimetric biosensors
Author(s)
Advisor
Okyay, Ali KemalDate
2012Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
Despite lots of research going on to find a hope, cancer is still a major cause of
death in today‘s world. It has been reported that cancer has some biomarkers in
human body and detecting these biomarkers timely can pave the way for early
detection and successful treatments.
Point-of-care biosensors are highly promising for this mission. If these
biosensors can achieve sensitivity and reliability with a low-cost and simple
platform, they can address a large mass of people who are at the early stages of
cancer without any clear symptoms yet.
For this purpose, various biosensing mechanisms can be used to convert the
signal coming from the recognition elements on the biosensor surface to the
digital domain for signal processing. One of these mechanisms, impedimetric
(impedance based) sensing is a very appealing electrical biosensing method
since this method can offer label-free, low-cost, low-power requirement,
miniaturizable, and chip-integrable detection platforms. However, impedimetric
sensing in liquid medium is problematic, since during the electrical
measurements, ion-based undesired layers (electrical double layers) are formed
over the electrodes in the target liquid. Unfortunately, these layers act like a
shield against the applied electric field to the liquid and can prevent the
detection of the target biomarkers.
In this thesis, a nanogap based label-free biosensor structure is designed and
using this design impedimetric sensing in liquid medium is demonstrated at low
frequencies (1 kHz – 100 kHz). Low frequency platforms are quite amenable to
low-cost applications like point-of-care biosensing.
The designed structure utilizes nanometer scale electrode separation
(nanogap). Theoretical calculations show that nanogap reduces the undesired
effect of electrical double layer. Moreover, nanogap also helps in minimizing
the volume of the required liquid for the measurement.
Design, fabrication, surface functionalization and biotinylation stages of the
biosensor are realized in a cleanroom environment and biomimetic materials
laboratory. The fabricated biosensor is tested by introducing the target
molecules (streptavidin) in a phosphate-buffered saline solution. A parameter
analyzer with a capacitance-voltage unit and a probe station are used for the
impedance measurements.
With these biosensors, label-free detection of streptavidin is observed for
100 µg/mL, 10 µg/mL, 1 µg/mL, 100 ng/mL and 10 ng/mL concentrations. This
is, to the best of our knowledge, the first demonstration of streptavidin detection
in nanogap based label-free impedimetric biosensors. The above-mentioned
concentrations show that these biosensors are promising for commercial
applications. Sensitivity to the dielectric constant of the target medium is
measured to be 132 pF per unit change in the dielectric constant at 10 kHz
measurement frequency. Reliability tests are performed: stable and repeatable
operation of the sensors are checked and verified.
In conclusion, this proof-of-concept study shows that nanogap based
biosensors would be a suitable and appealing choice for sensitive, reliable,
simple, low-power and low-cost point-of care biosensing applications. Next step
would be utilizing the platform presented in this work in detecting specific
cancer biomarkers like PSA or CA125. Thereby, developed further and
commercialized, nanogap based label-free impedimetric biosensors can act in
the battle of human being against cancer in the future.
Keywords
BiosensorEarly detection
Point-of-care detection
İmpedimetric
Nanogap
Label-free
Electrical double layer
Cancer
Streptavidin
Biotin