New aptamer based sensors will lead to cheap ultra-portable blood
20 September 2011
The University of Toledo in Ohio has developed a low-cost,
portable technique that is able to quickly and reliably detect specific
proteins in a sample of human blood.
This innovative technique, which uses artificial strands of nucleic
acid called aptamers, could
help in a wide range of medical sensing applications, including
diagnosing diseases like cancer and diabetes long before clinical
“The detection and measurement of specific blood proteins can
have a huge impact on numerous applications in medical diagnostic
sensing,” says Brent D. Cameron with the department of
bioengineering at the University of Toledo, one of the paper’s
authors. “This method has the potential to provide similar
functionality of large and costly clinical instrumentation currently
used to identify and quantify blood proteins for a fraction of
Human blood contains literally thousands of different proteins.
Many are essential for the day-to-day mechanics of life. Others are
formed only in response to certain diseases. Knowing which protein
is the hallmark of an illness and singling it out of a blood sample
leads to earlier diagnosis and more effective treatment. An example
of this is the prostate-specific antigen (PSA), which is now
routinely tested for to help detect prostate cancer and other
prostate abnormalities in men.
In this new system, the researchers borrowed a trick from nature,
using artificially created molecules called aptamers to latch on to
free-floating proteins in the blood. Aptamers are custom-made and
commercially available short strands of nucleic acid. In some ways,
they mimic the natural behavior of antibodies found in the body
because they connect to one type of molecule, and only one type.
Specific aptamers can be used to search for target compounds ranging
from small molecules — such as drugs and dyes — to complex
biological molecules such as enzymes, peptides, and proteins.
Aptamers, however, have advantages over antibodies in clinical
testing. They are able to tolerate a wide range of pH (acid and base
environments) and salt concentrations. They have high heat
stability, are easily synthesized, and cost efficient.
For their demonstration, the researchers chose thrombin and
thrombin-binding aptamers. Thrombin is a naturally occurring protein
in humans that plays a role in clotting.
The researchers affixed the aptamers to a sensor surface, in this
case a glass slide coated with a nanoscale layer of gold. As the
blood sample is applied to the testing surface, the aptamer and
their corresponding proteins latched together.
The next step is to actually determine if the couples pairing was
successful. To make this detection, the researchers used a real-time
optical sensing technique known as Surface Plasmon Resonance (SPR).
A surface plasmon is a “virtual particle”, created by the
wave-motion of electrons on the surface of the sensor. If the
protein is present and has bound to the aptamer, conditions for
which resonance will occur at the gold layer will change. This
resonance change is detected through a simple reflectance technique
that is coupled to a linear detector.
Expanded view of the aptamer-functionalised
resonance gold chip surface.
“By monitoring these conditions, we can quantify the amount of
the target protein that is present; even at very low
concentrations,” says Cameron. “This approach is very robust in that
unique aptamers for almost any given protein can be identified. This
makes the technique very specific and adaptable for any given
application.” The approach also requires less-bulky optics, which is
the key to the portability aspect of the design.
Aptamer sensors, according to the researchers, are also capable
of being reversibly denatured, meaning they can easily release their
target molecules, which makes them perfect receptors for biosensing
“The advantage of this surface plasmon sensor,” says Cameron, “is
that it enabled us to demonstrate low sample consumption, high
sensitivity, and fast response time.” The direct detection of blood
proteins in this manner can benefit a number of scientific and
clinical applications, such as monitoring diabetes, drug research,
environmental monitoring, and cancer diagnosis.
For commercial use in medical diagnostics, according to Cameron,
the technology is three to five years away, pending FDA procedures
and filings. “The time frame is very dependent on the target
application area. We are currently in the procedure of determining
suitable aptamers for a range of target proteins for both diabetic
and cancer-related applications,” he says.
Cameron BD et al. Development of a highly specific
amine-terminated aptamer functionalized surface plasmon resonance
biosensor for selective blood protein detection," Biomedical
Optics Express, Volume 2, Issue 9, pp. 2731-2740.