Development and fabrication of functional layers for cardiac biosensor application
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Date
2019
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Abstract
In this work, several types of biosensors are fabricated, characterized, and utilized
for the reliable and accurate detection of speci c biomolecules that playing
a crucial role in biochemical processes inside the human organism. During
the work, di erent types of biosensing techniques, including whispering-gallerymode
(WGM) resonators and eld-e ect transistors (FETs), as well as electrolyteinsulator-
semiconductor (EIS) sensors were introduced and used as highly sensitive
tools to study a set of biomolecules that are of particular interest for the understanding
of heart dysfunctions and for cardiac disease diagnosis.
A whispering{gallery{mode resonator with Zeonex-based micro
uidic channel was
designed for complex permittivity measurements of biological and chemical liquids.
The WGM technique allows to obtain a distinct di erence of resonance characteristics
between calibration liquids: water, acetone, methanol, ethanol, and propanol
in the
uidic chamber. Moreover, high sensitivity detection was achieved in the
study of the system's response to aqueous solutions of glutathione and ascorbate,
the two most important antioxidant-speci c biomarkers, with concentrations down
to 10 µg/L.
The capacitive electrolyte-insulator-semiconductor sensors, where silicon is covered
with a thin dielectric layer is exposed to liquid analyte solution, represents a reproducible
and extremely sensitive technique. Robust surface modi cation protocols
have been developed for the immobilization of speci c antibodies onto the topmost
ultra-thin silicon dioxide layer, consequently attributing to the C-reactive protein
(CRP) and Troponin biomarkers with di erent concentrations down to 1 µg/L.
Moreover, the introduction of aptamers, instead of antibodies, onto the surface of
EIS biosensors allowed to demonstrate an extremely high sensitivity to biomarkers
with concentrations down to 0.01 µg/L.
Field-e ect transistor-based biosensors, including those made of silicon and graphene,
have also been used to study the C-reactive protein molecules as well as Troponin-I
molecules with concentrations down to 0.1 µg/L. The reusability of silicon-based
FET biosensors was shown to be of great advantage for biosensing. Meanwhile,
graphene-based FETs have been successfully used to study the dynamic processes
during the induced cardiac ischemia arrest in HL-1 cell culture, grown in the reservoir,
directly on top of the chip. The ndings open prospects for the detection of
ischemia at early stages, and monitoring of cardiac disease development in vivo.
Application of graphene material is essential for the development of such kind of
biosensing devices, since they can be easily fabricated in the form of
exible and
even stretchable devices for utilization as implantable structures into living tissue.
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Keywords
Cardiac, Biosensor, Silicon oxide, Si-NW, FETs, Graphene, HL-1, Cells, Ischemia