News from the ACS National Meeting: An MS immunoassay

News from the ACS National Meeting: An MS immunoassay ... Publication Date (Web): June 1, 2011. Cite this:Anal. Chemi. 69, 11, 341A-343A. View: PDF | ...
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Donald Hunt, professor of chemistry at the University of Virginia, will receive the Award in Division awards Chemical InstruPaul Bohn, Stanley Bruckenstein, Wiillam mentation, sponR Heineman, Donald Hunt, and Jonathan sored by the Dow Sweedler are this year's winners of the ACS Chemical ComDivision of Analytical Chemistry awards. All pany Foundation. but the Findeis Award, which wiil be given Hunt developed the technique of using at the Eastern Analytical Symposium in microcapillary HPLC in conjunction with November in Somerset, NJ, will be preelectrospray ionization triple quadrupole sented at special symposia at the ACS fall MS to characterize the primary structure national meeting in Las Vegas, NV. of proteins at the subpicomole level. He is working on extending the approach to the Paul Bohn, professor of chemistry at the ion trap University of Illinois atUrbana-ChamJonathan Sweedler, associate profespaign, will receive sor of chemistry at the Award in Specthe University of trochemical AnalyIllinois at Urbanasis, sponsored by Champaign, will Perkin Elmer. Bohn receive the Arthur uses laser-based F. Findeis Award optical spectroscopy coupled with integrated for Achievements optical excitation to probe the bulk and interby a Young Analytifacial structure of group HI through V semiconductors, plasma-deposited dielectrics, anc cal Scientist, sponsored by the Philip Morris Companies. Sweedler's research interorganic thin films. ests include measurement of neuroactive peptides at the cellular level and improvStanley Bruckenstein, professor of ing the detectability in nanoliterchemistry at the volume NMR, which can be coupled onState University of line to microseparation techniques New York at Buffalo, will receive the Award in ElecNEWS FROM THE trochemistry, sponACS NATIONAL MEETING sored by EG&G Princeton Applied Celia Henry reports from San Francisco Research. Bruckenstein is known for his work in developing rotating disk and ringPolymer with a disk electrochemical techniques, introducing potentiometric stripping analysis, sweet tooth using electrochemical gas membrane deBecause of the sheer magnitude of the tectors, applying MS to electrochemical population that suffers from diabetes, improblems, and using piezoelectric techplantable glucose sensors continue to be a niques to weigh submonolayer and worthy goal. Most glucose sensors are thicker films on electrodes in situ. enzymatic—based on the oxidation of glucose catalyzed by glucose oxidase. Such sensors are expensive and difficult to William R. Heineman, professor of manufacture, difficult to implement for chemistry at the continuous monitoring because they are University of Cincinnati, will receive inhibited by components in blood, and even more difficult to develop for implanthe Award for Extation because they are immunogenic and cellence in Teachunstable. Frances Arnold of the Departing, which is coment of Chemical Engineering at the Calisponsored by the Division of Analyti- fornia Institute of Technology said that these attributes leave room for the develcal Chemistry and DuPont. Heineman is opment of "robust nonbiologically based exploring new techniques for immobilizmaterials" as glucose sensors. ing biomolecules on electrode surfaces and coating polymers on surfaces to form Arnold described the preparation and sensors use of a synthetic glucose-sensing polyPEOPLE

mer that was created by molecular imprinting and based on the complexation of glucose diol to a Cu(II)-triazacyclononane complex. The complexation is practically instantaneous and reversible; cis-diols (but not trans-diols) bind readily, as verified with isothermal titration calorimetry—a trans-diol released only the heat of dilution, not enough to indicate binding. The metal complex does most of the recognition, but the polymer would have to be coupled to a proton detection mechanjsm optical or potentiometric for excun~ pig to perform as a glucose sensor. She described the polymer's response to potential interferences, saying that lactic acid does not pose a problem but that amino acids and carbonate can decrease the signal. By lowering the operating pH to < 9, the amino acid problem is reduced. In addition, the response of the polymer to glucose is much higher than its response to glucosamine. Arnold said that ideal windows for glucose sensing with the polymer would be around pH 8 and pH 12, because the buffer capacity of interstitial fluid is lower at those levels. Although, pH 12 would not present a problem for the nonbiological polymer, it would require adjusting the pH of samples; pH 8 represents a more physiological level. She expects that this polymer could make an implantable glucose sensor that is inexpensive to manufacture, robust, and less immunogenic than enzymatic glucose sensors. One potential drawback of the polymer is that the copper complex is not, in principle, very selective among cis-diol sugars. Glucose, however, is the main sugar in blood, so the nonselectivity should not be a problem.

An MS immunoassay The combination of immunoassay with MALDI-MS provides high sensitivity and unambiguous, simultaneous detection of the analytes of interest in a single assay. David Lubman and co-workers at the University of Michigan, in collaboration with David Rossi and Jerry Nordblom at ParkeDavis Pharmaceutical Research, have developed an on-probe MALDI-MS immunoassay in which they immobilize the antibodies on the probe tip, thereby eliminating the need to elute the antigen from a separate medium. They accomplished direct coupling by immobilizing the binding molecules on the MALDI probe surface with a nitrocel-

Analytical Chemistry News & Features, June 1, 1997 341 A

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RESEARCH UPDATE Moving analytes one at a time Recently, much effort has been placed into single-molecule detection, but that's only the back half of the problem. The question at the front end of the single-molecule (or single subcellular organelle, potentially more interesting) problem is how to manipulate the vesicle, mitochondrion, or DNA molecule in question. In the May 15 issue of Analytical Chemistry, Richard dare end doworkers at Stanford University described a sample manipulation and injection method for CE that allows them to selectively inject subcellular components or even single molecules into a capillary (Anal. Chem. 1197, 69,1801-07). "We think we have a very important advance for the detection of single molecules and ultrasmall volumes," Zare says. The samples that they are dealing with are typically on the order of femtoliters or attoliters. "An advantage of looking at single molecules is that it removes the ensemble and al-

lows you to look at rare phenomena that are otherwise hidden." The technique combines optical trapping—"laser tweezers"—with a tapered capillary that has an opening that is the same scale as the item being analyzed. Through the use of a vesicle as an example, the beam from a laser is brought to a focus on the target. The electric field induces a dipole on the vesicle and holds it where the electric field is strongest, namely the center of the focused laser beam. Zare likens the phenomenon to moths being attracted to theflameof a candle. The vesicle can then be moved to the inlet of a tapered CE capillary with the optical trap. The usual way to make capillaries with narrow openings is to etch the tip with hydrofluoric acid. However, etching makes the tips jagged and actually increases the inner diameter. Pulling a thinwalled 100-um i.d. capillary resulted in a smaller tip than etching a thick-walled 10-um i.d. capillary. In addition, the tapered capillary was smooth and rounded. An added advantage of the tapered capillaries was that pulling took less time than etching. The ultrasmall tips are especially important for measuring subcellular components. To ensure measuring only one vesicle, the tip diameter and vesicle must be approximately the same size. They applied suction to the capillary with a precision syringe and could inject and eject a single (10-pm diameter) vesicle, without damaging the membrane. Electrophoretic analysis of a smaller vesicle containing carboxyrhodamine 6G and fluorescein yielded only one peak indicating that the vesicle had not been lysed. The electropherogram however did give rise to a broad peak envelope that might indicate slight leakage of the components In addition to manoiiTOi-incr r a nl»K1 1II'p oOj XlCUVtrl I l l g In)lr t»-,