Spots key cardiac biomarker even in
very low concentrations, which can be a life-saver
A
low-cost, ultra-sensitive device that is capable of detecting the cardiac
biomarker troponin T protein has been fabricated by a research team from the
Indian Institute of Technology (IIT) Hyderabad. Troponin T is a cardiac protein
that is released into the bloodstream after a heart attack.
Unlike
the commercially available test that can detect the protein at nanogram per ml
concentration, this device can detect the protein at an extremely low
concentration of femto gram per ml. This could help pave the way for early
diagnosis of a heart attack, increasing a patient’s survival rate. It even has
the potential to be able to predict the onset of a heart attack.
Cost-effective
fabrication
Unlike
electrodes that are available, it costs very little to fabricate this
bioelectrode. This is because a commercially available substrate was used.
Further, very little antibody was needed to coat the electrode.
The
electrode was fabricated by depositing perovskite (zinc tin oxide) material
electrochemically onto the substrate (indium tin oxide coated polyethylene
terephthalate). Glassy carbon electrode coated with the same perovskite
material was then used as a control. Perovskite increases the volume-to-surface
area of the electrode, thereby increasing its sensitivity.
The
electrodes coated with perovskite were then functionalised to attract proteins.
To increase the specificity of the electrode to bind only to the troponin T
protein, the electrodes were decorated or coated with the troponin T antibody.
Test
findings
The
researchers added various concentrations of the biomarker (ranging from 1
femtogram per ml to 1 microgram per ml) to a buffer solution and measured the
impedance (effective resistance in alternating current). Says Prof. Shiv Govind
Singh from the Department of Electrical Engineering and corresponding author of
a paper published in the journal Analytical Methods , “Compared with
the current limit of detection, the bioelectrode was able to detect troponin T
even when it is 10,000 times less in concentration.”
When
the troponin antigen binds to the antibody present on the electrode, the
impedance increases. Adds Prof. Singh, “As more and more biomarker binds to the
antibody, there is increased impedance, which is what we measure.” After some
time, the electrode is saturated with the troponin protein, so no change in
impedance is seen.
The
researchers measured impedance using different concentrations of the protein.
They plan to use these impedance values to know the concentration of the
protein when testing actual blood samples. Says Prof. Singh, “We can measure
the impedance in real time. And by using a machine learning algorithm, we can
measure the concentration of the biomarker in the sample.”
To
test the selectivity of the bioelectrode to bind to the biomarker, the
researchers tested it on bovine serum albumin (BSA) and human serum albumin
(HSA).
Says
Patta Supraja from the Department of Electrical Engineering at IIT Hyderabad
and first author of the paper, “Only a slight change in relative resistance was
observed in the case of HSA and BSA as only a small amount of proteins [from
HSA and BSA] bind to the bioelectrode. This is unlike troponin where more
protein gets bound to the bioelectrode, leading to more impedance.”
She
adds, “We then tested for interference by mixing the same amount of biomarker
with either BSA or HSA. The sensor’s response was not adversely affected by
either BSA or HSA.” The bioelectrode also showed consistent values when
measurements were taken repeatedly using the same concentration of the
biomarker.
Focus
on miniaturisation
The
team is now working on how to miniaturise the readout instrument. Says Prof.
Singh, “We will soon be able to capture the signal using a circuit the size of
a chip. This will be connected to [a] mobile phone with an app that has a
machine learning algorithm for quantification of the troponin biomarker.” He
adds, “We will have the prototype ready in six months to one year.”
“We
will have a prototype ready in six months to one year.
Shiv
Govind Singh,
Department
of Electrical Engineering,
IIT
Hyderabad
