Biomedical Engineering Reference
In-Depth Information
use of more selective bioreceptors to the development of different types of optical-based
nanosensors and nano-biosensors capable of being implanted into individual cells. One
such advance in the last decade has been the development of nanoparticle-based opto-
chemical sensors and biosensors, with nanometer-scale sizes in all three dimensions. The
small dimensions of these sensors allow for the implantation of thousands of them within
an individual cell, allowing for the monitoring of many locations simultaneously. Since the
first such nanoparticle-based nanosensor was developed approximately a decade ago,
many different such sensors have been developed for single-cell analyses, based upon
different bioreceptors and transduction schemes. However, despite the large number of
nanoparticle-based sensors developed, each type can be classified into one of four different
classes: (1) quantum-dot-based nano-biosensors, (2) polymer-encapsulated nanosensors
(known as probes encapsulated by biologically localized embedding (PEBBLEs)), (3) phos-
pholipid-based nanosensors, and (4) SERS-based nanosensors.
3.2.2.1 Quantum-Dot-Based Nano-Biosensors
One of the earliest classes of nanoparticle-based nanosensors that were developed employ
semiconductor nanoparticles, known as quantum dots,
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attached to various biological
receptor molecules such as antibodies,
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oligonucleotides
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and many other
species
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that can be used to translocate these quantum dots to the location of interest
on or within a cell.
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The quantum dots used in these early nanosensors and the most
commonly employed to date are ZnS particles capped with CdSe. By varying the diameter
of these quantum dots the wavelength of maximum luminescence emission is shifted, with
nanometer variations in diameter resulting in shifts of tens of nanometer in the emission,
maximum.
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Additionally, by using quantum dots instead of conventional organic dyes,
these sensors exhibit much more intense emission and a greater degree of photostability,
which is important when trying to monitor changes in chemical or biochemical species con-
centrations over time. This high degree of photostability is a direct result of reduced pho-
tobleaching and photodegradation of the luminescent material, as the quantum dots are
much more robust than most organic dyes. While these nanosensors represent an excellent
tool for labeling or staining and obtaining qualitative information about cellular reactions,
it is often difficult or impossible to employ them in a conventional “on/off” sensing modal-
ity, as the quantum dots exhibit luminescence emission whether or not they are bound to
the analyte of interest. Additionally, these quantum-dot-based nanosensors and nano-
biosensors represent a potential problem for cellular analyses in terms of their biocompat-
ibility, since the materials used to fabricate these quantum dots (e.g., CdSe) are often toxic.
Because of the toxicity issues associated with Cd and Se as well as other materials that have
been used to fabricate quantum dots, a significant effort is currently underway in many
research groups to develop quantum dots composed of more biocompatible materials.
Another means of overcoming the potential toxicity issues associated with quantum-dot-
based nanosensors that is currently being investigated is to thoroughly coat the surface of
the quantum dots with biological receptor molecules. This prevents the semiconductor core
of the sensor from interacting with the cellular environment, thus allowing quantum-dot-
based nano-biosensors to perform long-term monitoring of cellular reactions or processes.
Recent results in this area are showing a great deal of promise in terms of overcoming the
toxicity of these nanoparticle-based nanosensors.
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3.2.2.2 Polymer-Encapsulated Nanosensors
Another early class of nanoparticle-based nanosensors that has already had a large impact
on the fields of cellular biology and biochemistry is known as PEBBLEs.
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These
