Editorial pubs.acs.org/acssensors
The Exciting World of Single Molecule Sensors
I
I recently wrote a review outlining the measurement challenges with single entity sensors in much more detail, and highlighted some of the incredibly innovative ways that address this challenge.1 We have also sought to classify these solutions into four categories, which are (1) rapid near-field measurements, as we see with developments in nanopore measurements,2 (2) massively parallel near-field measurements, where many nanoscale wells are sampled at the same time, (3) wide-field sampling, massively parallel near-field measurements, where a large sample volume is interrogated but captures analytes brought back to an array of nanowell, an approach exploited so successfully with the SiMoA technology of David Walt,3 and (4) wide-field measurement which possibly has yet to be realized but in which super-resolution microscopy holds some promise. So if there are significant challenges in developing single molecule sensors, why would one bother? The answer is that there are important practical reasons for developing single entity sensors. First, if you can detect one entity, you can develop sensors with the ultimate sensitivity. This is necessary as there are examples where a single virus or bacteria can cause problems and where single molecules can influence the fate of cellular networks. Second, if you can count single entities, sensors can be developed to be calibration free. Third, you can measure the heterogeneity within a samplesuch as a sample of cellsand provided you can differentiate the rare event from the noise, you can detect aberrant species that cause a pathology. Fourth, if you can measure single entities on a surface, not only will you be able to detect specific interactions with the sensing surface, but you may also be able to detect nonspecific interactions, and differentiate the two types of interactions. Or better still, you could develop sensing surfaces that can measure many different species simply by how they interact with the sensor at the single molecule level. This would change the entire paradigm of how a sensor is configured from one where highly specific receptors are searched for to receptors that have a selectivity for a class of analyte. To put it simply, single entity sensors could solve the three big challenges in sensing: sensitivity, selectivity, and calibration. We have already seen technologies that are starting to do that, and we are starting to see papers on this topic in ACS Sensors.4,5 It is an incredibly exciting time for sensing!
n the editorial for the June 2016 issue of the journal, I wrote about trends in the biosensing field that were evident from the World Congress of Biosensors in Sweden this year. Of these trends, the one that really excites me is the recent interest in the field of single molecule sensors. In August, I again traveled in Europe to attend three electrochemistry conferences and the science of single things was again a dominating theme. The third of these conferences was a Faraday Discussions meeting I helped organize. It was the first ever meeting on Single Entity Electrochemistry. The word entity here is the keyit was chosen to encompass the investigation, detection, and quantification of single molecules, particles, and cells all into a new field. The reason for doing this is that many of the challenges in developing measurement tools for single things are common whether they be molecules, particles, or cells. There are of course also important distinctions. In electrochemistry, for example, the current to arise from oxidation or reduction of a single molecule is somewhat more difficult to detect than that arising from a single particle. Single entity measurements and single entity sensors are not just the domain of electrochemistry. We are seeing exciting developments in optics, scanning probe microscopy, and mass spectrometry in this regard. In fact I feel this is an incredibly important time for measurement science. Why? Because we are at a turning point. Until the present, many developments in measurement science have seen instruments get more and more sensitive, such that the samples for analysis become smaller and smaller. We are now at the point where the measurement of single entities, even single molecules, are commonalthough one should be careful not to equate common with easy. Developing measurement tools that can measure less sample than that required for a single entity will rarely make sense. What does make sense is developing sensing tools that can monitor many single entities. This is because, even though measuring a single entity can allow you to learn amazing things about that entity, it does not allow you to perform quantitative analysis. To perform quantitative analysis requires the measurement of many entities in a sample volume large enough for you to be confident that the sample represents the bulk. This phrase “sample volume large enough for you to be confident that the sample represents the bulk” is the major challenge facing the development of single entity sensors that are suitable for quantitative analysis. This is because, most measurement tools for single entities perform the measurement in an incredibly small volume, such that at any one time, there is only one species in the sample. That is, most single entity measurement methods are near-field approaches. Near-field approaches create a challenge for quantitative analysis, because to measure many single entities requires counting these entities as they pass through the measurement volume one at a time. With the large sample volumes required for reliable sampling of low concentrations of species this can mean waiting an inordinately long time. © 2016 American Chemical Society
J. Justin Gooding, Editor-in-Chief The University of New South Wales, Sydney, Australia
Received: October 9, 2016 Published: October 28, 2016 1163
DOI: 10.1021/acssensors.6b00624 ACS Sens. 2016, 1, 1163−1164
ACS Sensors
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Editorial
AUTHOR INFORMATION
Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
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REFERENCES
(1) Gooding, J. J.; Gaus, K. Single-Molecule Sensors: Challenges and Opportunities for Quantitative Analysis. Angew. Chem., Int. Ed. 2016, 55, 11354−11366. (2) Freedman, K. J.; Otto, L. M.; Ivanov, A. P.; Barik, A.; Oh, S. H.; Edel, J. B. Nat. Commun. 2016, 7, 10217. (3) Rissin, D. M.; Kan, C. W.; Campbell, T. G.; Howes, S. C.; Fournier, D. R.; Song, L.; Piech, T.; Patel, P. P.; Chang, L.; Rivnak, A. J.; Ferrell, E. P.; Randall, J. D.; Provuncher, G. K.; Walt, D. R.; Duffy, D. C. Nat. Biotechnol. 2010, 28, 595−599. (4) Fahie, M. A.; Yang, B.; Pham, B.; Chen, M. ACS Sens. 2016, 1, 614−622. (5) Shi, X.; Gao, R.; Ying, Y. L.; Si, W.; Chen, Y. F.; Long, Y. T. ACS Sens. 2016, 1, 1086−1090.
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DOI: 10.1021/acssensors.6b00624 ACS Sens. 2016, 1, 1163−1164
