Better Nanopores which can identify individual molecules
Nanoscience is a fascinating domain, which presents vast opportunities and challenges for developing new technologies which can go beyond our expectations. One of these technological advancements are Nanopores, which are nanometer-scale biosensing systems, which basically detect biomolecules, like DNA, drugs, detection of illnesses, and other applications. Nanopore sensors allow biomolecules to be analyzed with subnanometer resolution and without the need for amplification.
Now researchers have spent over 30 years developing and studying miniature biosensors which can identify single molecules, this sensing provides label-free and high-throughput detection, as well as the ability to modify the local environments with voltage and temperature. These devices have the potential to become a staple in clinics, they detect molecular markers of cancer and other illnesses and the effectiveness of drug treatments.
Scientists need to take into account the speed and speed of these measurements and find ways to better understand how molecules interact with these sensors, and for that researchers at the National Institute of Standards and Technology (NIST) and Virginia Commonwealth University (VCU) have developed a new approach. The team built a biosensor by creating an artificial version of the biomaterial that forms the cell membrane. Known as Lipid Bilayer, it contains small pores about 2 nanometers in diameter surrounded by fluids, and the ions which are dissolved in the fluid flow through the nanopores and generate a small electric current, but when a molecule which is of interest say a molecule which we wan to detect is driven into the membrane, the current flow stops, it's blocked, and the duration and size of this blockade acts as an identification system, identifying the size and properties of a particular molecule.
To accurately measure a large number of individual molecules, the molecule of interest is in the nanopore in the range of one hundred millionths to one-tenth of a second. The minimum energy required to break the barrier varies from molecule type to molecule and is important for the efficient and accurate functioning of the biosensor. Calculation of this amount involves measuring some properties related to the energy of the molecule as it enters and exits the pores. It is important to measure whether the interaction between the molecule and its environment results primarily from chemical bonds or from the ability of the molecule to move in small steps and move freely throughout the capture and release process.
So far reliable measurements for extracting these energy components have been lacking for many technical reasons. A study demonstrated that laser-based high-speed heating can measure these engines. Measurements must be performed at different temperatures, and these temperature changes occur quickly and reproducibly, which allows researchers to complete measurements in less than two minutes, whereas compared to 30 minutes or more for other methods.
Without the new laser-based heating tool, the measurements won't take place, says Joseph Robertson, from NIST.
When energy measurements are performed they help clarify how the numerator interacts with the nanopores, and this can be used to strategize to detect the molecules to the fullest capacity it will be able to. Like say if a molecule only interacts with nanopores only via chemical interactions, so to achieve the goldilocks capture time, researchers experimented with modifying the nanopores so that the electrostatic attraction to the target molecule was not too strong or too weak.
Researchers have demonstrated a method using two small peptides, which are the short chains of a compound that make up the protein's constituents, one of the peptides, angiotensin, stabilizes blood pressure, and another peptide, neurotensin, helps regulate the mood-affecting neurotransmitter dopamine and may also play a role in colorectal cancer. These molecules interact with nanopores primarily through electrostatic forces. The researchers inserted into the nanopore gold nanoparticles capped with a charged material that boosted the electrostatic interactions with the molecules. The team also examined another molecule, polyethylene glycol, whose ability to move determines how much time it spends in the nanopore. Ordinarily, this molecule can wiggle, rotate and stretch freely, unencumbered by its environment. To increase the molecule's residence time in the nanopore, the researchers altered the nanopore's shape, making it more difficult for the molecule to squeeze through the tiny cavity and exit.
Robertson said that they can exploit these changes to build a nanopore biosensor tailored to detect specific molecules. A research laboratory can employ such a biosensor to identify molecules of interest or a doctor's office could use the device to identify diseases.
Paper: Christopher E. Angevine, Joseph W.F. Robertson, Amala Dass, and Joseph E. Reiner. Laser-based temperature control to study the roles of entropy and enthalpy in polymer-nanopore interactions. Science Advances. Published online April 21, 2021. DOI: 10.1124626/sciadv.abf5462
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