| Posted: Sep 19, 2017 |
Copying nature's lock-and-key system could improve rapid medical diagnostics
(Nanowerk News) A team from Imperial College London have developed a nanoscale sensor that can selectively detect protein molecules at the single-molecule level, which could help in early stage clinical diagnosis.
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When analysing body fluid samples for signals of a disease, scientists are often looking for very rare molecules within a complex mixture. In order to find such ‘needles in a haystack’, scientists often use methods that detect single molecules at a time.
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One promising technology is nanopore sensing, where individual molecules are passed through a very small nanometer-sized hole. This process results in each molecule producing its own unique signature, without the need for lengthy sample preparation or chemical modification.
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However, different molecules of the same size can produce very similar signals, making it hard to uniquely identify the target molecule.
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To solve this problem, a team led by Imperial College London have developed a system based on a nanopore and a nanoscale transistor, which can recognise target molecules in a similar way to biological receptors. The details of their new system are published today in Nature Communications ("Nanopore Extended Field Effect Transistor for Selective Single Molecule Biosensing").
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| Researchers have designed a system that rapidly recognises the specific biological molecules that can indicate disease.
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Lock and key
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Receptors recognise molecules with particular shapes and bind to them in a lock-and-key mechanism. In this study, the nanoscale transistor was made from a polymer material that could be imprinted with a binding site – ‘the lock’. This allows the system to detect the only matching ‘key’ – a specific target molecule.
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To test that the system works as expected, the team used it to detect the antibody that binds to insulin, a mechanism important in the diagnosis of diabetes. However, the team say that the system design can also be readily applied in the detection to a much broader range of biological molecules.
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Co-author of the study Professor Joshua Edel, from the Department of Chemistry at Imperial, said: “We have shown that we can imprint a polymer at the entrance to the nanopore with the shape of the natural ‘lock’ to the ‘key’ molecule we are looking for, mimicking biological receptors.”
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Opening and closing the gate
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The researchers also added another feature to the new system to solve another problem in nanopore sensing: if molecules pass too quickly through the nanopore, they may not get detected.
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They added an electrode attached to the polymer coating of the pore, forming a nanoscale transistor, to which a voltage could be applied. This makes the pore act like a gate – the applied voltage can ‘open’ or ‘close’ the gate, controlling the transport of molecules through the pore.
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Dr Aleksandar Ivanov, from the Department of Chemistry at Imperial, said: “We now have a truly tuneable biosensor. By adding new complexity into the system we can control the transport of molecules and can have longer time to study a specific molecule.”
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Professor Yuri Korchev, from the Department of Medicine at Imperial, added: “The complete system combines concentration, tuneable speed and selectivity, which will be clinically relevant in the search for rare proteins such as specific kinds of antibodies and DNA molecules.”
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