Researchers at Arizona State University are working on a device that can be used to identify molecules without the need for expensive equipment or vast quantities of samples. The researchers have used electron tunneling to identify carbohydrates at the molecular level. They basically zap the molecules with electricity and are able to identify molecules in the sample from current fluctuations. The researchers have already been able to identify amino acids and peptides with their new technique and believe they can identify individual sugars.
Carbohydrates – monosaccharides, oligosaccharides and polysaccharides – are one of the four building blocks of life. Monosaccharides – sugars – can exist in two different anomers, while each of those anomers can form a wide range of epimers. The potential number of different combinations is enormous, especially in the case of linear monosaccharides containing multiple sugar molecules. In fact, there are about a trillion different ways to connect six sugar molecules.
The presence of certain sugars in tissue samples can be indicative of disease; however, to identify these sugars, scientists require access to expensive equipment and lab tests usually require a large number of samples for NMR characterization. Isomers can also be very difficult to separate. While mass spectrometry can be used to identify molecules, it cannot be used to distinguish between two different forms of the same molecule if they are the same molecular weight, at least not without further chemical analysis.
The researchers have found that their new electron tunneling technique – called recognition tunneling – allows them to classify many different anomers and epimers of sugars. The different molecules are recognized from detected fluctuations in current when they are zapped with electricity in a tunnel junction functionalized with recognition molecules. The technique can be used to identify carbohydrates at the single-molecule level.
Further, the researchers claim they only need tiny quantities of analyte. Only sub-picomole quantities are required for analysis. The researchers say they are able to use the recognition tunneling technique to count the number of molecules in a population of coexisting isomers, and that it is possible to resolve isomers that are poorly separated by ion-mobility. The technique can also be used to detect glycosylation of a peptide. The researchers say recognition tunneling could be used to sequence linear polysaccharides on a nanoscale level by integrating recognition tunneling into a nanopore.
Recognition tunneling can be used to discriminate between different saccharides at the single molecule level, therefore it is possible to detect markers for cancer such as the Tn antigen and O-GlcNAcylation in a protein sample. In a recent paper announcing the new technique, the researchers say “RT is clearly capable of providing a key component of a single-molecule sequencing system for linear oligosaccharides, a presently almost intractable problem.”
The technique has limitations. An appropriate database would need to be compiled to identify a broad range of compounds, but the researchers believe the technique could prove invaluable for disease detection.