Synthetic nanodetectors for specific molecules
A new type of molecular detector, which can be rapidly manufactured and screened, has recently been introduced by scientists at MIT. In a paper published Nov. 24 in Nature Nanotechnology, a large team led by Michael Strano show that specific polymers without inherent molecular recognition abilities selectively recognize small molecules such as the vitamin riboflavin and the hormone estradiol when adsorbed to carbon nanotubes. By single-molecule fluorescent imaging and molecular dynamics simulations, the authors show that adsorption alters the polymer’s structure, creating new potential binding sites. If future work allows cost-effective design of polymer-nanotube detectors for specific molecules, the researchers speculate that these complexes could become an alternative to antibodies for everything from biological research to diagnostic assays to drug targeting.
Whether this novel platform will have such wide-ranging uses will remain unknown for some time; the results so far provided are a proof-of-concept that polymer-nanotube complexes can be rapidly screened for recognition. Among ~30 random polymers adsorbed to carbon nanotubes for binding to 36 small molecules (indicated by changes in the fluorescence of the carbon nanotubes), the MIT group discovered 3 that selectively recognized just one. While binding specificity could not be predicted based on a polymer’s structure prior to this study, the imaging and simulation approach the team developed may enable such prediction in the future. Further, binding affinity between a specific analyte and polymer-nanotube complex can be improved by tuning polymer chemistry and nanotube diameter. The fact that numerous variables influence binding affinity suggests that a polymer- nanotube sensor could be designed for almost any analyte.
Molecular recognition principle. Adsorption of polymer to carbon nanotubes (i) creates binding sites for analytes, and binding (ii) changes the nanotube's fluorescence. Reprinted by permission from Macmillan Publishers Ltd: [Nature Nanotech] (8, 896-7), copyright 2013.
This work builds on prior use of nanotube complexes to detect specific molecules; the novelty of this study lies in its open-ended approach. Rather than using enzymes, complementary DNA, or other chemical groups known to bind specific molecules, these researchers used an arbitrary set of polymers—that these complexes would selectively bind any of the target molecules was not entirely expected.
While the Strano group aims to provide a synthetic means of molecular recognition, which they speculate would be more consistent and less expensive than antibodies, carbon nanotube expert Davide Bonifazi expects a more limited set of applications, such as binding-triggered drug release, in his review of the article. A system that combines sensing and response would require development of a means of translating the electronic change in the carbon to a mechanical change in the drug-containing component. He also cautions that the current variability in carbon nanotube structure would limit the consistency of these sensors. Even without these future applications, the fluorescent sensors themselves could prove useful for cell-based studies; the nanotube-polymer complexes allow real-time imaging of riboflavin diffusion within cells.