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Nonbiological Inhibition-Based Sensing (NIBS) Demonstrated for the Detection of Toxic Sulfides Chelsea N. Monty, Nicolas J. London˜o, and Richard I. Masel* Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 The purpose of this paper is to report on a new technique in chemical detection: nonbiological inhibition-based sensing (NIBS). This method uses a new approach to chemical amplification, where the analyte inhibits rather than enhances the rate of catalytic reaction. Although there are many possible catalysts for this technique, such as enzymes, this paper focuses on using the selective binding found in colorimetric detection. Colorimetric methods are selective; however, they are not particularly sensitive. Using nonbiological-based molecules allows for selective detection without the shelf-life issues that are associated with enzymes. In practice, we can use the active substances in Draeger tubes and related systems as catalysts. Analytes of interest inhibit the catalysts that leads to a large signal. The work presented here focuses on the detection of toxic sulfide compounds. Using NIBS, we observe that we can enhance the sensitivity of the system by 2 orders of magnitude with no apparent loss in selectivity. We can also decrease the detection time from 5 h to 10 min. So far, we have demonstrated the technique for sulfide detection; however, we believe that the technique can have general use in the detection of toxic compounds. The purpose of this work is to demonstrate a new type of sensor, where inhibition of a catalytic reaction is used as a way to chemically amplify the analytical signal from an analyte molecule. By way of background, Blaedel and co-workers1-5 pioneered the idea of using chemical amplification to increase the sensitivity of an analytical measurement. Blaedel’s group showed that if one can find a reaction that is catalyzed by an analyte of interest, the increase in the reaction rate can be used as a sensitive measure of the concentration of the analyte. Each analyte molecule catalyzes the formation of thousands of product molecules. Consequently, the sensitivity of the measurement can be enhanced by thousands. Blaedel’s approach has become standard in atmospheric analysis and has also been demonstrated in other systems.6-10 In the work described in this paper, we have developed a new approach to chemical amplification. Instead of using the analyte * To whom correspondence should be addressed. E-mail:
[email protected]. (1) Blaedel, W. J.; Petitjean, D. L. Anal. Chem. 1958, 30, 1958–1965. (2) Blaedel, W. J.; Hicks, G. P. Anal. Biochem. 1962, 4, 476–488. (3) Blaedel, W. J.; Hicks, G. P. Anal. Chem. 1962, 34, 388–394. (4) Blaedel, W. J.; Olson, C. Anal. Chem. 1964, 36, 343–347. (5) Blaedel, W. J.; Boguslaski, R. C. Anal. Chem. 1978, 50, 1026–1032.
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as a catalyst, we use the analyte as an inhibitor for a given reaction. In detail, we find reactions A f B that are catalyzed by a catalyst C, where C selectively binds an analyte of interest. A small change in the concentration of the analyte produces a large change in the concentrations of A and B. Consequently, the signal from the analyte is amplified. There are many possible catalysts that one can use; enzymes, for example, work well for chemical amplification but suffer from shelf-life issues. One example of biological inhibition-based sensing uses cholinesterase inhibition to detect phosphoric acid esters in the parts-per-billion (ppb) range.11-15 In place of biomolecules, we have been concentrating on using materials found in Draeger tubes and other related colorimetric methods as catalysts. Draeger tubes are already reasonably selective to analytes of interest, but they are not particularly sensitive. We hypothesized that, if we use the chemicals in a Draeger tube or related colorimetric methods as catalysts in a chemical amplification system, we could retain the selectivity of the colorimetric method but obtain a much higher sensitivity. We call this technique nonbiological inhibitionbased sensing (NIBS), because we are using the inhibition of a non-biological-based catalyst as a sensing mechanism. In the work here, we demonstrate the success of this technique for the detection of 2-chloroethyl methyl sulfide (CEMS). Detectors for toxic sulfide compounds are of special interest, because of the ability of these compounds to alkylate DNA, resulting in cell death or cancer in humans and other organisms. There are already many portable sensors available for CEMS and related compounds, including ion mobility spectrometers (IMSs),16-18 surface acoustic wave (SAW) array sensors,19-22 surface-enhanced (6) Weinheimer, A. J. Anal. Tech. Atmos. Meas. 2006, 311–360. (7) Kuznetsov, V. V.; Ermolenko, Y. V.; Bykhovskii, M. L.; Sheremet’ev, S. V. J. Anal. Chem. 2002, 57, 843–851. (8) Rajagopalan, S. R. Bull. Mater. Sci. 1983, 5, 317–322. (9) Van Antwerp, W. P.; Mastrototoro, J. J.; Lane, S. M.; Satcher, J. H.; Darrow, C. B.; Peyser, T. A.; Harder, J. World Patent WO/1998/022820, May 28, 1998. (10) Regehr, M. F. J. Capillary Electrophor. 1996, 3, 117–124. (11) Bather, W. Sens. Update 1998, 4, 82–108. (12) Amine, A.; Mohammadi, H.; Bourais, I.; Palleschi, G. Biosens. Bioelectron. 2006, 21, 1405–1423. (13) Andreescu, S.; Noguer, T.; Magearu, V.; Marty, J. L. Talanta 2002, 57, 169–176. (14) Andreescu, S.; Avramescu, A.; Bala, C.; Magearu, V.; Marty, J.-L. Anal. Bioanal. Chem. 2002, 374, 39–45. (15) Botre, F.; Lorenti, G.; Mazzei, F.; Simonetti, G.; Porcelli, F.; Botre, C.; Scibona, G. Sens. Actuators, B 1994, 19, 689–693. (16) Groenewold, G. S.; Appelhans, A. D.; Ingram, J. C. In Proceedings of the ERDEC Scientific Conference on Chemical and Biological Defense Research, Aberdeen Proving Ground, MD, November 18-21, 1997; Published in 1998; pp 531-537. 10.1021/ac9009353 CCC: $40.75 2009 American Chemical Society Published on Web 07/02/2009
Scheme 1
Raman spectroscopy (SERS) systems,23-25 resistance-based sensors,26,27 and colorimetric techniques; however, they all have limitations. For example, IMS and SERS equipment are not small enough to be mounted in a wearable sensor. A wearable sensor is defined as a small, lightweight (
