n e w s

ANALYTICAL CURRENTS

Low-affinity complexes

How good is electrospray ionization MS stants for ligand-to-complex ratios rang - lieved to be hydrogen bound to the (ESI-MS) at detecting weakly bound ing from 1:1 to 4:1 were determined. RNA. Finally, this tour de force study complexes? Richard Griffey and col - However, the is even more reports the relative gas-phase activation leagues at Ibis Therapeutics report a complex, because 2-DOS binds to two energies for the dissociation of a series spectrum of a complex held together distinct sites on 16S. To investigate the of ligand–16S complexes. ( J. Am. Chem. by a single hydrogen bond. They also stability of these two forms, the re - Soc. 2000, 122, 9933–9938) describe the binding stoichiometry for searchers turned to colli - complexes of multiple ligands with RNA sionally activated dissocia - and an example where a ligand binds to tion and MS/MS. By 16S [M-5H+]5- two different sites. The key is choosing varying the relative disso - the right conditions for the ESI-MS ciation energy, the com - experiment. plex was dissociated into The experiments focus on low-affinity the 1:1 complex and the complexes formed with a 27-nucleotide free 16S and 2-DOS ions. 16S + 2-DOS RNA model of the 16S rRNA A-site MS also revealed multi - (16S). As a first step, the researchers ad - ple different ligands con - 16S + DT just the “harshness” of ESI-MS condi - currently binding 16S. 16S + 2-DOS + DT tions by looking for the spectrum of One particularly complex ammonia-adducted ions of 16S. This experiment found the 16S + (2-DOS)5 spectrum appears by either lowering mono- and bis-ligand the capillary–skimmer potential or the complexes of 2-DOS and desolvation capillary temperature. 16S, plus a complex with 1720 1740 1760 1780 m/z Binding of the ligand 2-deoxystrept - 2-DOS and a diaminotria - Low-affinity complexes galore. ESI-FT ion cyclotron reso - amine (2-DOS) was the basis of several zole simultaneously bound nance mass spectrum showing the concurrent binding of experiments. In one, dissociation con - to 16S. The triazole is be - 2-DOS and 3,5-diaminotriazole to 16S.

Dynamics with a tracer Here is a handy trick. David Padowitz and Ben - monolayer. However, they use scanning tun - central methylene group in the carbon chain jamin Messmore of Amherst College investi - neling microscopy (STM), which is too slow to with either a sulfur (thioether) or oxygen gate exchange between long-chain molecules follow the dynamics of individual molecules. To (ether), are mixed with the alkane or with in solution and those arranged as a surface get around this problem, they introduce a trac - each other in a ~1:10 ratio. The mixture co- er molecule that allows the exchange to be fol - crystallizes on the graphite surface, and the lowed by the “slow-moving” STM. heteroatom is easily viewed.

The system under investigation is the C 33 H68 The researchers find that the sulfur is par - molecule n-tritriacontane, which is adsorbed ticularly easy to track, and they can watch onto graphite. These molecules move on and the entire monolayer turn over in a few tens off the surface in milliseconds—much faster of seconds. The rate of exchange is deter - than the seconds required for an STM image. mined from the data, and the researchers Follow the bright dots. Two images tracking Instead of looking at individual molecules, speculate on the mechanism. They also see the thioethers on the surface. It takes 2 sec - onds to collect an STM image with a 2-sec - the researchers tracked the entire surface. different dynamics at the domain boundaries. ond delay between scans. To do that, tracer molecules, which replace a (J. Phys. Chem. B 2000, 43, 9943–9946)

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ANALYTICAL CURRENTS

A rainbow of molecular beacons

With the introduction of “wavelength- monochromatic light source. open, and, thus, the quencher and fluo - shifting” molecular beacons, the future Like traditional molecular beacons, rophore are apart. for these fluorescent probes looks espe - the wavelength-shifting version is a sin - However, there are two fluorophores cially bright, not to mention colorful. gle-stranded, hairpin-shaped oligonu - in the new molecular beacons—a “har - Sanjay Tyagi, Salvatore Marras, and cleotide probe that does not emit a sig - vester” that absorbs energy from the ex - Fred Kramer at the Public Health Re - nal when the hairpin is closed—that is, light and an “emitter” that re - search Institute in New York developed when the probe’s fluorophore and leases energy as a fluorescent signal. The the new probes, which emit light at var - quencher are close together. The signal emitter fluorophore is joined to the 5´- ious colors yet are excited by a single, becomes detectable when the hairpin is end of the probe by a short spacer se - quence, the length of which can be adjusted to optimize the fluorescence res onance energy transfer between the Measuring ligand–receptor forces two moieties. The researchers tested three wave - Cell–cell adhesion generally depends ducing receptor–ligand pairs. Depend- length-shifting molecular beacons. Each on specific binding between recep - ing on the force applied, the ruptur - one used fluorescein as the harvester; tors on the surface of one cell and ing of single or multiple receptor–li- the emitter was either 6-carboxyrhoda - ligands on the surface of another. gand bonds can be studied. mine 6G, tetramethylrhodamine, or The amounts of force needed to The researchers tested the setup Texas red. In all cases, the signal was

break apart these receptor–ligand using the integrin receptor ␣IIb ␤3 detected predominantly in the emission pairs are typically measured “in bulk” from blood platelets and artificial li- range of the emitter, not the harvester. using macroscopic methods or nano - gands and found that the unbinding In addition, the researchers note that probe techniques at the single mole - forces were much smaller than those the new molecular beacons were often cule level. To help develop a more measured in single molecule studies. brighter than conventional ones, and complete picture, E. Sackmann and The reason for the difference, the re - they attribute that change to more effi - colleagues at the University of Cali - searchers suggest, is that the new cient energy absorption. ( Nat. Biotech - fornia–Los Angeles, the MPI for Bio - method seems to measure leverage nol. 2000, 18, 1191–1196) chemistry (Germany), and the Tech - forces, which may break the recep - nische Universität München (Germany) tor–ligand bonds efficiently, whereas describe a middle-ground “mesoscop - other methods measure pure traction Cystic fibrosis diagnostic ic ” method for measuring lig - forces. ( Langmuir, 2000, 16, 8984– array and–receptor unbinding forces. 8993) In the new method, a “test cell”— Although some mutations that cause cystic in reality, an artificially formed giant fibrosis can be identified by genetic testing, B- vesicle—is immobilized on a substrate field the more universal diagnostic technique is via receptor–ligand binding. Then a N S magnetic bead is attached to the top the so-called sweat test, or more correctly, of the cell, and a vertical force of 0.1–2 pN is generated by pulling the pilocarpine iontophoresis test for elec - on the bead. Reflection interference θF trolytes in sweat. Although the sweat test is contrast microscopy monitors the c convenient and simple to administer, analyz - structure, and the magnitude and di - R rection of the forces are determined c θO ing the samples is not as easy. But Aogán c quantitatively. h Lynch, Dermot Diamond, and Matt Leader at The approach allows the measure - ment of unbinding forces under bio - Dublin City University (Ireland) and SENDX logically relevant conditions, the re - Medical, Inc., hope to change that with a searchers say. Because the cell is large , A “test cell” is held to a substrate by re - the “pinning center” holding it to ceptor–ligand binding. A magnetic bead potentiometric ion-selective microelectrode the substrate may be ~1000 Å across attached to the top of the cell allows a array that may replace techniques such as and may contain ~100 adhesion-pro - vertical force to be applied.

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flame photometry and anion exchange chro - a. matography. DNA detects lead cleavage site substrate strand 17DS The array used is produced commercially 3'–GTAGAGAAGGrATATCACTCA–5' Decades of genetic research are pay ing 5'–CATCTCTTCT ATAGTGAGT–3' C A and consists of solid-state microelectrodes off in unexpected ways. In this case, C A G A G T G a deoxyribozyme, which is a catalyti - C G C enzyme strand 17E screen-printed over a salt-doped hydrogel cally active DNA, is the basis of a se - G C 2+ b. 80000 lective Pb biosensor. According to III layer. To give a more comprehensive analysis, I Yi Lu and Jing Li of the University +Enz

the array simultaneously measures levels of y

t 60000 I of Illinois at Urbana–Champaign, this i II s

+ – n e 2+ Na and Cl , which are the two most reliable in - unique sensor boasts a >80-fold pref - t +Pb n i 2+ 40000 + erence for Pb over other common e c

dicators; K , which is often used to confirm the n III

metal ions and a quantifiable detection e c

2+ s II

e 20000

diagnosis; and other parameters, such as Ca , range of 10 nM–4 µM. Moreover, this r o u l approach suggests that a wealth of f pH, pO , and conductivity. The sample turn - 2 new biosensors can be developed, be - 0 570 600 630 660 690 around time was ~1 min, compared with sev - cause researchers can fish through vast wavelength (nm) libraries of random DNA or RNA seg - eral hours using current analysis techniques. ments for other recognition elements. (a) Proposed secondary structure of the + + – Cluster analyses of Na , K , and Cl levels The deoxyribozyme in this bio sen - deoxyribozyme (17E) and the substrate + sor cleaves a single RNA linkage in a (17DS); rA is a ribonucleotide adenosine. together and the Na levels alone in 21 sam - 2+ DNA substrate when activated by Pb . (b) Fluorescence spectra of (I) the sub - ples yielded well-defined clustering of posi - To make this work, the 5´-end of the strate alone and the enzyme with substrate 2+ tive and negative (normal) samples. Unfortu - substrate, a DNA/RNA chimera, was (II) before and (III) after adding 500 nM Pb . labeled with a fluorophore, and the – nately, the clustering for Cl alone, which is 3´-end of the deoxyribozyme was generally regarded as the best single marker linked to a quencher. The enzyme biosensor retained its selectivity to and substrate hybridized together, 500 nM Pb 2+ in the presence of equal for cystic fibrosis, was not as good because and the fluorescence was quenched; amounts of eight other divalent metal – the addition of Pb 2+ led to the cleav - ions and under simulated physiologi - of interference from NO 3 , which is typically age of the substrate and a ~400% in - cal conditions. ( J. Am. Chem. Soc. found in the reagent to stimulate sweat. crease in fluorescence intensity. The 2000, 122, 10466–10467) ( Analyst 2000, 125, 2264–2267)

RESEARCH PROFILES

Mercury micropumps

In the realm where millimeters loom Others have used surface tension to The Iowa researchers took a com - large, familiar forces such as gravity and pump small volumes of fluids, a concept pletely different approach, developing friction no longer reign. Instead, the known as the Marangoni effect. In the an electrochemically actuated mercury key to success is harnessing the lesser- earlier work, a surface tension gradient pump, which is described in the current known forces that have supplanted their was generated between two electrodes issue of (pp 103– macroscale oppressors. So when Marc that were positioned on the walls of a 110). Porter says the pump was inspired Porter, Jing Ni, Chuan-Jian Zhong, and channel. For example, water-soluble by the mercury beating heart, a com - Shelley Coldiron at Iowa State Univer - molecules might be transformed from a mon laboratory demonstration in which sity and the Ames Laboratory–U.S. De - surface-inactive state to a surface-active changes in the accumulated charge on partment of Energy wanted to make a state using electrochemical methods. the surface of a drop of mercury alter miniature pump, they abandoned me - Controlling this transformation would the surface tension. These changes in chanical methods and turned to surface control the surface pressure in the chan - surface tension, in turn, relax or contract tension. nel, which would drive the fluid. the curvature of the mercury drop. “This

JANUARY 1, 2001 / ANALYTICAL CHEMISTR Y 1 1 A n e w s

RESEARCH PROFILES

Fluid point, Porter explains. By applying a flow waveform voltage, the pump can be cy - cled between “fill” mode, in which the Electrochemical mercury in the inner column distends switching downward, and “pump” mode, in which E E the mercury in the inner column ex - tends upward, forcing liquid through E the flow channel. The magnitude of the voltage determines how much the height E of the inner mercury column changes, and the frequency of the waveform de - termines how fast the pump cycles. Once the researchers got the basic mechanism working, they arranged four Fill mode Pump mode mercury pumps, which can be actuated individually, in a series. The result is, ef - The “fill” and “pump” modes of the mercury pump. In fill mode, the mercury in the inner column fectively, a miniature mercury peristaltic distends downward. In pump mode, the mercury in the inner column extends upward, displac - pump with four pistons, which drives ing fluid in the flow channel at the top. Applying a step voltage switches between the modes. the fluid in one direction, Porter says. These days, the researchers are trying to reduce the scale of the mercury pump property is pretty unique to mercury capillary that will fit into the reservoir; from millimeters to several hundred mi - because it’s a liquid metal,” says Porter. the horizontal section is the flow channel, crometers. In addition, they are trying “Although you can do the same thing which intersects the capillary. After mer - to figure out how to prevent the mer- with gallium, you have to work at high - cury and an aqueous electrolyte are added cury from coming in contact with the er temperatures, so it is not as practical to the reservoir, the insert is fitted on top. sample. “We’ve been using a thin Teflon or easy to study.” Capillary action then draws mercury into membrane that would push the liquid,” In thinking about the mercury beat - the insert, resulting in two concentric Porter explains, “but we don’t have the ing heart, the researchers realized that mercury col umns. At this point, the rela - right material yet. The ones we have used “if you’re changing the shape, you’re tive heights of the two columns reflect so far are too stiff.” doing physical work,” Porter explains. the balance between capillary forces and Nevertheless, the researchers are en - The question then became how to har - gravity, Porter says. couraged by their results so far and even ness that shape change into a mecha - To activate the pump, a voltage is ap - hope to fly the pump on NASA’s micro - nism that would actuate fluid flow. After plied across two electrodes—one in con - gravity plane one day. Porter notes that performing some calculations to be sure tact with the mercury at the bottom of the team will probably first try a simpler that the idea was sound and trying a the reservoir, and the other in contact experiment on the microgravity plane to few options, the researchers hit on an with the electrolyte at the top of the get used to working with fluids under approach that worked. reservoir. The application of the voltage those conditions. “But the mercury pump The “proof-of-concept” pump has two changes the surface tension in the outer work was supported by NASA,” he adds, parts: an open-topped main reservoir and mercury column, which leads to a pres - “so we would like to be able to use it in a T-shaped capillary insert. The vertical sure change, and the mercury levels in that environment at some point.” section of the T is an open- bottomed both columns shift to a new equilibrium –Elizabeth Zubritsky

“Four-decay” DNA sequencing

Four-color DNA sequencing is the back - 5873): a “four-decay” scheme, which have increased sequencing throughput bone of every genome project, but most relies on frequency-domain fluorescence 4-fold, because they allow all four base four-color sequencing schemes are only lifetime detection for multiplexed DNA reactions to be run simultaneously in a ~90% accurate. So Linda McGown and sequencing. single lane. But there is inevitably emis - Hui He at Duke University describe a Four-color fluorescence techniques— sion overlap that produces errors in new alternative in the December 15 in which the four fluorescent tags are reading the fluorescence spectrum and, issue of Analytical Chemistry (pp 5865– identified by their emission spectra— thus, misidentification of bases.

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In contrast to color-discrimination se - and 98.5% with three, but technical limi - PCR. “But that can run into problems quencing, McGown turned to time-re - tations prevented them from accom - with sample overloading, so we’re work - solved fluorescence, which measures the plishing the technique using all four. ing on improving the detection limits.” amount of time it takes the excited dye “It’s due to data analysis and propaga - There are still other challenges ahead. to return to the ground state and emit a tion of error,” says McGown. Overcom - “We need a better four-dye system,” says photon. It produces a distinct signature ing this limitation, she adds, “is just a McGown. At 488 nm, the researchers that follows first order kinetics, making matter of improving the data analysis could get four dyes that had good, in - it far easier to interpret the data. “In a strategy.” tense signals and resolvable lifetimes. sense, it’s the difference between a line The successful application of the life - “The only problem was that one dye is spectrum and a band spectrum,” says time-resolved technique with four base much larger than the others, so we had McGown. “Would you rather resolve pairs wouldn’t just improve accuracy, it mobility problems [on the electrophero - four lines or four broad spectral peaks?” should also allow researchers to examine gram],” she explains. “You get [one Applying the time-resolved method larger fragments, McGown says. That base] migrating at a different rate.” to DNA sequencing “just seemed like a would, in turn, increase accuracy and Even so, the bottom line is that the natural,” McGown says. But finding sets speed by cutting down on the number system could decrease errors in genome of four dyes that could withstand the of enzymatic digestion steps. sequencing, especially if the researchers conditions of the sequencing reactions was challenging be - cause most dyes currently Total Intensity T (Cy3) C (TMR) in use have similar lifetimes. “The companies focus on 20 40 60 80 100 120 140 1.0

making dyes with different ) s t i

colors rather than different n U

lifetimes,” she explains. Mc - y

r 0.5 a

Gown finally settled on two r t i b

sets of dyes—one that is ex - r A ( cited at 488 nm and the ) y 0.0 t s i n

other at 514 nm. s ( n

1500 1600 1700 1800 1900 2000 2100 2200 2300 2400 2500 2600 e e

Once the bands have been t m i n t I

separated, McGown’s team e f e 1.0 160 180 200 220 240 260 280 300 i c L

uses a continuous laser with n e

a modulated frequency to c s e e xcite the dyes. The fre - r

o 0.5 u quency of the emitted pho - l F ton decreases relative to the frequency of the excitation 0.0 laser, with longer fluorescent lifetimes leading to a greater 2600 2700 2800 2900 3000 3100 3200 3300 3400 3500 3600 3700 3800 3900 4000 shift. Those readouts have Migration Time (s) yielded an accuracy of 96% for reading DNA fragments Lifetime-resolved intensity peaks of C-terminated fragments labeled with TMR (blue) and T-terminated ranging from 41 to 220 fragments labeled with Cy3 (red). Total intensity is shown in black. bases. The team also used Fourier transform data analysis in an attempt to The one disadvantage of the current can make improvements in the instru - separate the frequency spectrum into the system is that the lifetime fluorescent mentation. “[The new method] has a individual components representing all measurement attenuates the signal, which lot of potential to be scaled down into four dyes. Just as with color detection, hurts the detection limit. The difference a simpler, dedicated detection instru - there is some spectral overlap because “depends on several factors, but . . . ment,” she explains. “I’d like to im - the fragments, especially longer ones, could be roughly an order of magni - prove its accessibility . . . to make it don’t always completely separate on tude,” says McGown. The obvious way simpler to incorporate into routine the electropherogram. The researchers to compensate, she explains, is to use methodology.” achieved 99% accuracy with two dyes more sample, perhaps amplifying it with –Jim Kling

JANUARY 1, 2001 / ANALYTICAL CHEMISTR Y 1 3 A n e w s

RESEARCH PROFILES

Chip-based mosaic immunoassays

For immunoassays, the perpetual goal is area, protein-based assays have generally hundreds of amino acids. (Antibodies to increase throughput by reducing the been more difficult than DNA-based as - generally have ~1400 amino acids.) In amount of reagent consumed, shorten - says to miniaturize and integrate into addition, proteins can easily lose their ing the incubation time, and performing smaller, highly sensitive, practical formats, three-dimensional structure when han - more assays at once. In the current issue Delamarche says. For example, gridlike dled under “denaturing” conditions. of Analytical Chemistry (pp 8–12), Em - patterns of DNA oligonucleotides can be The key to making the microfabricat - manuel Delamarche, André Bernard, “built” on a surface using photolithogra - ed device work was the ability to deposit and Bruno Michel at IBM’s Zurich phy, but the same is not possible for pro - the proteins with a high resolution, says Research Laboratory (Switzerland) teins, because they can be composed of Bernard. To do this, researchers have describe a new method for used various approaches, includ - doing just that. They call ing inkjet printing, drop-on-de - their approach microfabri- A Immobilization Channels mand techniques, microcontact cated mosaic (“micromosa - printing, and soft lithography, Antigen 1 ic”) immunoassays and re - which is what the IBM team Antigen 2 port that the assays consume µ chose. “What is really pleasing FN Flow only nanoliter quantities of to see,” Delamarche says, “is reagents and perform incuba - Substrate that soft lithography not only tions within a few seconds or B Blocking has the potential to help micro - minutes. fabrication, but it can handle N The works draws upon an fragile proteins and pattern them S ongoing effort, led by Michel, BSA on a surface.” which is centered around mi - In preliminary experiments, crocontact processing to de - C Recognition the sensitivity and reliability of velop microfabricated devices. the new approach compared well θF The researchers abandon mi - with those of traditional immuno - c crowells, which are tradition - assays , the researchers say. In the ally used for immunoassays, simple case of two-step assays 1 2 3 in favor of a flat le le le (antigen–antibody pairs), binding Rc mp mp mp θO poly(dimethylsiloxane) sub - Sa Sa Sa and detection occurred over a c h strate, onto which they de - D Reading mosaic concentration range of <1–1000 posit narrow stripes of antigen nM. More sophisticated sand - using a network of microflu - wich-type assays (such as en - idic channels fabricated in sili - zyme-linked immunosorbent as - con. Then, a second network says) could also be performed, of microchannels, perpendicu - E Example with one pair of antigen and antibody and in these cases, the signal in - lar to the first, delivers the so - tensity could be scaled with the lutions to be analyzed. (The amount of analyte present. researchers use simple capil - Another encouraging finding lary forces to induce flow in was that dilute solutions of pro - the channels.) Binding the teins could be used. Proteins analytes results in a mosaic from the solution are deposited pat tern of tiny squares—simi - onto the surface of the substrate lar to the grids of dots seen as the solution flows inside the with DNA microarrays— microchannel, Delamarche ex - which can be analyzed with a 100 µm plains. The challenge is that solu - fluo rescence microscope. tions of proteins are typically di - Researchers have long rec - Strategy for performing a micromosaic immunoassay. (A) Antigens lute, and the volume is typically ognized the value of such a are deposited in stripes. (B) Blocking with bovine serum albumin small—possibly less than a nano - microarray-type format for im - to prevent nonspecific binding. (C) Antibodies are al lowed to bind. liter, depending on the geometry munoassays. However, despite (D) A mosaic binding pattern results. (E) An array of rabbit immuno - of the channel. To ensure that some recent success in this globulin Gs (IgGs) interacting with anti-rabbit-IgGs. enough proteins flow through

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the microchannel to entirely coat the crowells typically wait 30 min while the The researchers note that no blinded exposed region of the substrate, the re - proteins slowly diffuse in all directions, experiments were performed (although, searchers place a spongelike flow-pro - including toward the surface, but inside in some cases, unexpected cross-reactivi - moting pad at the far end of every mi - the device’s 10-µm-high microchannels, ty—in which antibodies from one species crochannel. As the dry pad soaks up the diffusion path of the protein from recognized and bound to antibodies solution, it helps draw fluid through the solution to the surface is consider - from another species—was observed). the channel. ably smaller. Most of the proteins will The reason, Delamarche explains, is that The short coating and binding times diffuse to the surface of the substrate “we were not comfortable developing seen for this device are a result of the within seconds and adsorb. “By per - this work on unknown ground.” How - small channel dimensions, which pre - forming both the patterned delivery ever, now that the preliminary work is vent mass transport limitations. “This of antigens and antibodies to a surface finished, the team will start using real- point is really important, and most peo - using microchannels, we make an im - life samples to better evaluate the diag - ple don’t realize it,” Delamarche says. portant economy of solutions, of pro - nostic potential of the technique. People doing conventional assays in mi - teins, and time,” Delamarche adds. –Sandra Katzman

MEETING NEWS

2000 Eastern Analytical Symposium—Gerald Keller reports from Atlantic City, NJ. Trace atmospheric gases on a shoestring

The necessity of cost control in the analyt - excite the fiber, and the liquid-filled waveguides. An ical laboratory is a nagging problem. But resulting count could be advantage of this approach Purnendu “Sandy” Dasgupta of Texas taken a safe distance away. is that the reaction is often Tech University has a solution, at least Later, the fibers were filled carried out in the wave - for measuring some trace atmospheric with fluorescent dyes. guide. This approach side - gases: liquid-core waveguide instruments Cheap to produce, with steps any loss of lumines - that smash the usual financial barriers a long shelf-life, the wave - cence and signal strength and rival the sensitivity of much more guides made their way to on the way to the detector, expensive spectroscopic instruments. the hobby- and education- which may be a significant

If you want to measure H 2S or CO, centric Edmund Scientific problem during fast reac - then a variety of systems, some of them Co. There they languished tions in other instruments. disposable, are available from sources as in the catalog, which de - For this reason, faster convenient as the local hardware store. scribed them as having no Penny-pinching wave - throughput is also possible But if you want to measure sub-parts- known practical use. guides. with the new sensors. per-billion levels of formaldehyde, am - Dasgupta purchased one By selecting from a va - monia, or less frequently monitored and was observing the green riety of dyes and prereac - gasses, Dasgupta’s fiber-optic threads glow from its end in his artificially lit lab - tions that can take place outside or with - may be the way to go. The sensors are oratory. He then walked down the par - in the waveguide, different analytes such based on readily available scintillating tially sunlit hallway and out into direct as ammonia, hydrogen peroxide, and optical fibers, which are constructed of a sunlight, all the time watching the green formaldehyde can be detected, and the fluoropolymer ( Anal. Chem. 1999, 71, glow intensify. Puzzled that the intensi - researchers are now working on detect - 1400–1407). When a light-excitation ty, but not the color, changed with the ing hydrogen sulfide and other gases source is applied to the side of the tube, excitation light, he consulted a colleague (Anal. Chem. 2000, 72, 5338–5347). light propagates down its length and can who noted simply that the dye, fluores - After examining several excitation sources, be quantified with a relatively inexpensive cein, always glows green. This suggested Dasgupta’s favorite was the common, in - photodetector. to Dasgupta that properties of the exci - expensive, light-emitting diodes (LEDs) The idea came from waveguides that tation light would not carry over into found at the local electronics supply store, were filled with a special scintillation the emitted light, eliminating a source and with the advent of near-UV and violet compound and produced for radiation of detector interference that plagues con - diode lasers and LEDs, he suggests that detection. A radioactive source would ventional methods. He translated this into the new approach may really take off.

JANUARY 1, 2001 / ANALYTICAL CHEMISTR Y 1 5 A n e w s

BUSINESS

DNA diagnostic business growing

The molecular and cytogenetic disease- DNA Diagnostic Business , published in market for genetic disease testing, and testing procedure market is estimated to October 2000 by Business Communica - new disease-specific sequencing proce - be $66.3 million in the year 2000 and tions Company, Inc. (www.bccresearch. dures are continually being developed. exceed $100 million in 2005, according com). Sequencing and PCR techniques In particular, fluorescent in situ hy - to a new market research report, The remain a large and growing part of the bridization (FISH) cytogenetic genetic disease-testing procedures are growing fast, with an average annual growth rate of 12.3% domestically and 13% interna - Packard plunges deeper into life sciences tionally. One of the most rapidly expand - ing cytogenetic areas is Her-2/Neu Right now, the place to be is in the well, a spokesperson for Packard Bio - FISH testing for breast cancer. Consid - life sciences market. The production Science. “One technology will create erable investments also are being made of bio chip and microarray technology the chip, [and] the other will analyze in emerging markets, such as newborn has become a focus for many instru - it,” she says. Packard also announced screening and preimplantation diagno - ment companies, including Packard plans to sell its Canberra Industries sis. Among the DNA diagnostic tech - BioScience. subsidiary, which has focused on nu - nologies currently experiencing a large clear measurement instrumentation, growth in research and development are says Jason Alter, Packard’s director MS and biochips. of business development. In addition to providing market Packard is also collaborating with analyses, the report profiles several other companies that are breaking com panies in the DNA diagnostic into the life sciences market. The two business, including some instrument most publicized collaborations are com panies, and discusses some recent with Motorola and Oxford Glyco - gene and technology patent disputes. In an effort to solidify itself in the Sciences. In 1999, Packard licensed A section on single nucleotide poly- life sciences market, Packard acquired its high-through put inkjet printing morphism (SNP) research, including GSLI Life Sciences in October 2000 technology to Motorola, a producer the SNP Consortium and database, is and created the spin-off company of three-dimensional bioarrays. The also included. Packard BioChip Technologies. The collaboration with Oxford, which is –Laura Ruth new company is made up of an instru - known for its proteomics work and ments division and a ventures division. producing protein biochips, represents The GSLI acquisition falls under the a more forward-looking approach by ventures division, which plans to com - Packard. “No technologies are being bine Packard’s piezoelectric printing exchanged between the companies in technology with the confocal laser the deal, but rather, both companies technology of GSLI to produce bio- have agreed to jointly explore the fea - chips and microarrays. Nevertheless, sibility of producing protein biochips,” the two technologies will be used in - says Alter. dependently, according to Tricia Cald - –Wilder Smith

PEOPLE

New Advisory Board and A-Page Advisory Panel members appointed

Eight new members from government, board is a vital link between the editors Division of Analytical Chemistry serves academia, and industry have been se - and the analytical chemistry community. a 1-year term as ex officio representative lected to serve 3-year terms on Analyt - Each January, membership is rotated as of the Division. ical Chemistry ’s Editorial Advisory new appointees replace members whose Ira Levin, acting director, Division of Board. Established in the 1940s, the terms have expired. The chair of the ACS Intramural Research, and chief of Molec -

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PEOPLE

ular Biophysics in the clude using biological MS for determin - interests include IR and Raman vibra - National Institute of ing the structures of small molecules, tional spectroscopy of polymeric sys - Diabetes and Diges - identifying protein sequences, and de - tems, and vibrational micro scopy and tive and Kidney Dis - veloping new high-throughput screen - imaging using near-field techniques. eases at the National ing methods. Institutes of Health, A-Page Advisory Panel received his B.S. de - Mark Wightman, Analytical Chemistry has also se lected gree from the Uni - professor at the Uni - nine new members to serve 3-year terms versity of Virginia and his Ph.D. from versity of North Car - on its A-Page Advisory Panel. Brown University. Levin’s research inter - olina–Chapel Hill, re - ests include vibrational spectroscopic stud - ceived his B.A. from Dermont Dia- ies involving lipid–protein interactions and Erskine College and mond, associate di - domain structures in biological membranes his Ph.D. from the rector of the Nation - and the development of IR, Raman, and University of North al Centre for Sensor spectroscopic imaging techniques. Carolina. His research interests include Research at Dublin the development of microsensors and City University (Ire - Victoria McGuf- microelectrode-based techniques, and land), received his fin, professor at the investigations of neurotransmitters. Ph.D. at Queen’s Michigan State Uni - University Belfast (Ireland). His research versity, received her Richard Sacks, interests include the design, characteriza - B.A. degree from professor at the Uni - tion, and synthesis of molecular receptors, Eastern Michigan versity of Michigan, and the development of rapid, multi- University and her received his B.S. de - anayte sensing systems, which use elec - Ph.D. from Indiana gree from the Uni - trochemical and optical sensor arrays. University. Her research interests include versity of Illinois and the theory and practice of capillary LC his Ph.D. from the Carol Robinson, and CE, the development of novel laser- University of Wiscon - professor and direc - based spectroscopic detectors, and the use sin. His research interests include instru - tor of MS at the of computer simulation methods in sepa - ments and strategies for high-speed GC, Oxford Centre for ration science and applied spectroscopy. columns with tunable and programma - Molecular Sciences, ble selectivity, and TOFMS for rapid received her Ph.D. Peter Schoen- characterization of organic compounds. from the University makers, professor of Cambridge (U.K.). at the University John Frenz, di - Her research interests include applying of Amsterdam (The rector of manufactur - MS to structural biology; investigating Netherlands) and ing science and tech - the mechanisms of protein folding, mis - principal research nology at Genentech, folding, and disease; and assembling at the Shell received his Ph.D. in macromolecular complexes. Research and Tech - chemical engineering nology Centre in Amsterdam, received from Yale University. Klaus-Dieter his Ph.D. from the Technical University His research interests Franz, head of Cen - in Delft (The Netherlands). His research include both upstream and downstream tral Analytical Ser v- interests include separation techniques, production of recombinant protein phar - ices of Merck KGaA systematic optimization strategies, and maceuticals, protein chromatography, (Germany), received applications of artificial intelligence. process monitoring, and data analysis. his Ph.D. from the University of Frank - Barbara Larsen, Bruce Chase, furt (Germany). His a senior research as - senior research fellow research interests include hyphenated sociate at DuPont, at DuPont, received methods, automation, chemometrics, received her Ph.D. his B.S. from Williams miniaturization, and information tech - from the University College and his Ph.D. nologies in analytical science. of Delaware. Larsen’s from Princeton Uni - research interests in - versity. His research Hubert Girault, professor at the

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Ecole Polytechnique Robert Dunn, chromatography. Federale de Lausanne associate professor Bayer is known for (Switzerland), receiv - at the University of his work in capillary ed his Ph.D. from Kansas, received his HPLC, CE, capillary the University of Ph.D. from the Uni - electrochromatogra - Southampton (Eng - versity of California– phy, and coupling land). His research San Diego. His re- these techniques on- interests include search interests in - line with MS and the study of charge-transfer reactions clude the study of protein channel dynam - NMR. at soft interfaces and the development ics, artificial membrane systems, single of micro analytical devices for protein molecule spectroscopy, and the develop - Csaba Horváth, analysis. ment of new microscopy methods. professor at Yale Uni - versity, will receive Neils Heegaard, Rachel Loo, the ACS Award in head of research and research associate at Separations Science development in the Pfizer Global, receiv - and Technology, autoimmunology ed her B.S. degree sponsored by IBC Advanced Technolo - department at the from the University gies and Millipore. The award recognizes Statens Serum In- of Wiscon - outstanding accomplishments in funda - stitut (), sin–Madison and her mental or applied separation science and received his M.D. Ph.D. from Cornell techno logy. Horváth is known for his work and D.Sc. from the University of Copen - Uni versity. Her research interests in clude in capillary electro chromatography, bio - hagen (Denmark). His research interests applying MS to biology, gel elec - polymer separations, nonlinear chro ma - include the development and application trophoresis, and antibacterial drug dis - to graphy, and high- of microanalytical methods to study li- covery. speed HPLC. gand binding to proteins and peptides. 2001 ACS awards Helmut Schwarz, Edgar Arriaga, Several scientists in the analytical chem - professor at the Tech - assistant professor istry community will receive the 2001 nische Universität at the University of American Chemical Society awards at the Berlin (Germany), Minnesota, received 221st National Meeting in San Diego, will receive the Frank his Ph.D. from Dal - CA, in the spring. H. Field and Joe L. housie University Franklin Award for Outstanding Achieve - (). His re - Klaus Biemann, ment in , sponsored search interests in - professor at the Mas - by Bruker Daltonics. Schwarz is known clude organelle analysis based on CE; sachusetts Institute for his work in reaction mechanisms at micrototal analysis systems; and MS for of Technology, will the molecular level and in the intrinsic characterizing subcellular interactions, re ceive the ACS properties of elusive drug trafficking, and proteomic strategies. Award in Analytical species. Chemistry, spon - S. Michael sored by Fisher Scientific. The award is William Klem- Angel, associate pro - given in recognition of outstanding con - perer, professor at fessor at the Univer - tributions to pure or applied analytical Harvard, will receive sity of South Caroli - chemistry. Biemann is known for his the E. Bright Wilson na, received his Ph.D. work in four-sector tandem MS, laser Award in Spectro - from North Carolina desorption MS, and the first GC/MS scopy, sponsored by State University. His and computer techniques. Rohm and Haas. The award recognizes research interests in - fundamental and applied contributions clude developing methods for remote Ernst Bayer, professor at the Uni - in all fields of spectroscopy. Klemperer and in situ chemical analysis using spec - vesität Tübingen (Germany), will receive is known for his work in the geometric troscopic techniques (e.g., Raman and the ACS Award in Chroma to graphy, and electronic structures of van der Waals laser-induced breakdown spectroscopy) sponsored by Supelco. The award recog - molecules and weakly bound complexes and fiber-optic chemical sensors. nizes specific achievements in the field of and modeling the kinetic behavior of the

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