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Spotting a disease in its earliest stages can help to facilitate its treatment greatly, yet telltale clues are often hidden at a scale too small to study accurately. This hindrance has some researchers looking for ways to use high-powered atomic force microscopes (AFMs) to study individual molecules for disease markers

"The greatest bottleneck in my work is the ability to handle molecules in such a way that does not produce false positives or negatives," says Ozgur Sahin, a junior fellow at Harvard's Rowland Institute. Sahin uses an AFM to measure intermolecular forces and provides that data to other scientists. "We can't be sure whether what we're measuring comes from a single molecule or a group of molecules," he says.

Sahin came across a technology he believes has potential to help researchers work with greater precision, improving the accuracy of nanoscale measurements. The material is a nanoparticle coating called NanoCone that is made by Westlake Village, Calif.–based Nanogea, Inc. NanoCone is used to coat AFM probes and the substrates on which samples are placed with cone-shaped nanoparticles that lift and separate individual molecules so they can more easily and accurately be measured. Sahin discovered Nanogea research papers describing their technology while he was searching the Web for new technologies that might improve the accuracy and efficiency of his AFM.

Biological molecules have a recognition capability, Sahin says, adding, "They know to which molecules they want to bind, but our ability to handle these individual molecules is limited by our surface chemistry. Ideally you want to do the experiment where you examine molecules one by one."

An AFM is like a record player, says Saul Tendler, pro vice chancellor and professor of biophysical chemistry at the University of Nottingham's School of Pharmacy in England. It has a sharp probe needle that interrogates a surface, taking either topography measurements or measuring the force of interactions between molecules. "If you have a molecule on a substrate that recognizes a molecule on the probe, you get a molecular interaction," explains Tendler, who also serves on Nanogea's scientific advisory board and holds a joint patent with Nanogea co-founder and chief science officer Joon Won Park. "As you pull back you can measure the force of that interaction."

AFMs function as analytical tools that enable researchers to detect molecules that are key markers for diseases such as cancer, Alzheimer's and hepatitis C, Tendler says. More important, an AFM can alert researchers to the presence of these markers in the bloodstream or elsewhere even when they appear in very small amounts, indicating the disease is at an early stage.

Nanogea can fabricate its NanoCone coating to adhere to different surfaces by making the cones using shorter or longer carbon chains, so as to match the molecules being studied. The coating is also applied to the probe's tip so that it can capture a separated molecule and probe it in detail.

The company is in the process of convincing different AFM manufacturers to offer NanoCone coating with their devices. Once the coating is added to an AFM probe, the NanoCones cannot be removed. "You have different tips for different applications," says Nanogea co-founder, CEO and president David Sun. He adds that a coated probe could be used "tens of thousands" of times before needing replacement.

https://www.scientificamerican.com/article/nanocone-afm/