Editorial Cite This: ACS Sens. 2019, 4, 528−528
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What Does Ultrasensitive Really Mean?
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picomolar detection limits”. This is a compromise between the chemical and biological meaning of sensitivity that acknowledges the link between the chemical meaning of detection limit, and sensitivity as it relates to the background signal. So, what of the subpicomolar detection limit we refer to? Why was that chosen? The argument we presented was that subpicomolar represents concentration levels relevant to many disease biomarkers including cancer markers in the blood, blood-borne bacteria, and viral infections. These are biomarkers in areas where there is currently an unmet sensor need, as elegantly discussed by ACS Sensors editor Shana Kelley (DOI: 10.1021/acssensors.6b00691). This definition of ultrasensitive biosensorsas those that have subpicomolar detection limitsmay not be everyone’s ideal, but we hope it is at least a workable definition.
ltrasensitive is a word that is progressively being used more as a descriptor in relation to sensors. A Web of Science search suggests that the first use of the term in a title was in a 1971 sensor paper published in Applied Physics Letters1 entitled “Miniature Ultrasensitive Superconducting Magnetic Gradiometer and its Use in Cardiography and Other Applications”. The first chemical sensing paper I found with “ultrasensitive” in the title was in a 1996 Analytical Chemistry paper:2 “Conductive polymer films as ultrasensitive chemical sensors for hydrazine and monomethylhydrazine vapor”. The use of this adjective has risen rapidly since those early days; now a search for papers published in 2018 containing both “ultrasensitive” and “sensors” returns 934 papers. So, what does it actually mean if a sensor is “ultrasensitive”? It is a difficult term to defineeven more so with biosensors. Why? It all comes down to the meaning of the word “sensitive”. It means different things to a chemist versus a biologist, and so, confusion arises in interdisciplinary research. The IUPAC definition from the Gold bookwhich chemists should use defines sensitivity as the “slope of the calibration curve”, and hence the ability of an analytical method to discriminate between small changes in concentration. A detection limiton the other handis the “minimum single result, which with a stated probability, can be distinguished from a suitable blank value”. But in biochemistry, sensitivity is defined differently; it is a measure of how strong a stimulus has to be, before a system reacts to itthe smaller the stimulus required to elicit a reaction, the more sensitive a system is. So, the definition for biochemists sounds similar to what a chemist calls a detection limit. If we turn our attention back to the first ultrasensitive chemical sensing paper in Analytical Chemistry,2 they referred to “ultrasensitive analyte detection” as below parts per billion, or lower, concentrations. So, in fact, “ultrasensitive” in this paper relates to detection limits rather than the slope of the calibration curve. I was recently invited to write a perspective for J. Am. Chem. Soc. on ultrasensitive biosensors.3 As part of this I really wanted to try and clarify what exactly an ultrasensitive biosensor is. In the first submission, one of the referees pointed out that I was confusing sensitivity with detection limit. As discussed above, the confusion is almost inevitable in the biosensing field owing to the interdisciplinary nature, especially with the strong biological influence. And as shown from even the very first mention of the term “ultrasensitive” in chemical sensing,2 the word has been synonymous with low detection limits. The referee of my paper was right, of course, from a chemist’s perspective. I was somewhat embarrassed at the time, as for a long time I was an advocate for using the correct chemical terms, but somewhere along the way I had begun to associate sensitivity with detection limit. Which brings me to the point of this Editorial: What should we classify as an ultrasensitive biosensor considering the interdisciplinarity? In our Perspective paper we defined an ultrasensitive bioanalytical sensor as “a biosensor with sufficient sensitivity and low background to allow sub© 2019 American Chemical Society
J. Justin Gooding
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The University of New South Wales, Sydney, Australia
AUTHOR INFORMATION
ORCID
J. Justin Gooding: 0000-0002-5398-0597 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) Zimmerman, J. E.; Frederick, N. V. Appl. Phys. Lett. 1971, 19, 16−19. (2) Ellis, D. L.; Zakin, M. R.; Bernstein, L. S.; Rubner, M. F. Anal. Chem. 1996, 68, 817−822. (3) Wu, Y.; Tilley, R. D.; Gooding, J. J. J. Am. Chem. Soc. 2019, 141, 1162−1170.
Received: February 26, 2019 Published: March 22, 2019 528
DOI: 10.1021/acssensors.9b00404 ACS Sens. 2019, 4, 528−528
