when it comes to studying the likes of poly- scientists. "Our method is bringing tandem ethylene glycol or polymethylmethacrylate mass spectrometry to polymers," says Derin detail, even the most robust analytical rick. "We obtain detailed structural infortechnique breaks down. On p 3637, Peter J. mation on the sequence of monomers makDerrick and co-workers at the University of ing up a polymer chain as well as salient Warwick (U.K.) discuss a new variation on end-group information." Derrick's use of the MS theme, which will help bring a bet- the word "sequence", which is usually reter understanding of polymers and the poserved for protein chains and DNA strands, lymerization process. Ultimately, with synhints at the new technique's power. Schematic representation of the microchipthetic polymers under the analytical umThe team can obtain this unprecenanoelectrospray tip assembly. brella, creating novel "designer" polymers dented detail from their polymer samples will be possible. using high-energy collisions in the mass spectrometer, which can probe all internal "Polymers are becoming much more time scales to enhance sensitivity. "The bonds without paying any regard to relative sophisticated in terms of molecular design, sensitivity from the nanospray tips is nostrengths. A novel TOF technology, which and the relationships between molecular ticeably better than what we have seen structure and physical properties are becom- is designed to avoid restricting collision from a channel orifice at the edge of a miing clearer," Derrick explained to Analytical energies to low values, then measures the crochip," Ramsey says. "We believe that Chemistry. "The need is to firm up this struc- collision products, so structural informasome type of tip is needed for many highture/property relationship," he added, "then tion can be deduced. sensitivity applications." However, she adds, in areas such as combinatorial library we will be able to design and synthesize the The main area of application includes structures we need for a particular use." Der- designer polymers and synthetic biomicertification, where sample concentrations rick and his team started out developing are high, a channel orifice could provide metic polymers. "We are thinking of conmatrix-assisted laser desorption techniques satisfactory results. trol of chemical composition, topology and that would help them characterize the end tacticity, as well as molecular mass distriOther groups (e.g., those led by Barry groups and structures of various natural butions," explains Derrick. The ease with Karger at Northeastern University and D. compounds. A fortuitous change of tack, which structural information might now be Jed Harrison at the University of Alberta) forced on them by dwindling reagent supobtained will facilitate the task of testing have also shown that there are advantages in attaching capillaries to chips for ESI-MS, plies made them realize that their prototype experimental polymerization schemes and instrument might be better suited for synallow chemists to fine-tune reaction according to Mike Ramsey. "We may not schemes to produce the desired end prodhave yet realized the optimum approach for thetic and biomimetic polymers. uct with less trial and error. including electrospray tips on lab-on-a-chip Gel-permeation chromatography ducks devices," he says, "but it seems clear that the whole "intricate structure" question by Derrick and David Haddleton present chips with tips are better for ESI-MS." providing molecular masses, as long as the preliminary results demonstrating the technique's power at determining the endElizabeth Zubritsky broad structural features of the polymers are known, says Derrick. group functionalities of various strains of polyethylene glycol. "End groups," Derrick By coupling MALDI with high-energy Getting the measure collision-induced points out, "affect durability and degradadissociation, Derrick and tion directly and play an important role in his team have found that they are starting of polymers the final bulk polymer properties." to bring to polymer chemistry a level of For all their complexity, biopolymers are detail that is usually the domain of protein not too difficult to characterize. However, David Bradley
NEWS FROM BIOMEMS Elizabeth Zubritsky reports from San Francisco, CA.
Living chips The canary in the coal mine has gone biotech. Colin Brenan, Tanya Kanigan, Karel Domansky, and colleagues in Ian Hunter's and Linda Griffith's groups at the Massachusetts Institute of Technology are developing the modern equivalents of the classic biosensor: cell- and tissue-based sensors on microchips. The focus of the project is to detect biological or chemical warfare agents, but Brenan says the work is branching out
to high-throughput screening, environmental monitoring, and clinical diagnosis. "There are a number of ways to do these sorts of things chemically," Brenan says. "The advantage of a biological sensor ... is that you detect the agent and determine what the effect will be." He adds that this approach may provide better detection limits. Whereas a single virus would go unnoticed in many chemical methods, it may be enough to trigger a cellular response he says. In the typical cell-based device, yeast is cultured in an array of 500- to 2000-umdeep wells (diameter = 200 um) machined
into a silicon or other substrate. To keep the fluids from each well separated on this "living chip", the substrate surface is hydrophobic, and the wells are hydrophilic. However, by varying the surface finish and the substrate, the chips can be tailored for different applications, Brenan adds. Another way to tailor the chips is to genetically engineer the yeast cells. Hunter's group is creating an androgen receptor chip that can detect low levels of steroids, such as estrogen, which correlate with prostate cancer. In theory, different yeast variants could be
Analytical Chemistry News & Features, September 1, 1999 5 9 1 A
News
developed to test for herbicides and To preserve as much of the in vivo func- type of liver cell—from rats, but the pesticides. tion as possible, the researchers, led by goal is to use human cells and to add Chips with up to 120,000 wells have Linda Griffiths, are building microchip enother kinds of liver cells to the tissue. vironments that mimic a natural liver and, been made, suggesting the potential Brenan even envisions a day when artiif all goes well, allow normal metabolic for high-throughput screening and ficial livers based on these devices function. "When you look at the liver, the massively parallel discovery of new could be used as interim organs for cells are organized into intersecting plates, materials. The group uses fluorespeople awaiting transplants. and each cell is a certain distance from the cence detection to read the chips, but Brenan says he would classify the blood supply," Brenan explains. "Our Brenan says they are looking into work as "not necessarily" a micro-total structures recreate these conditions." mass spectrometry. analysis system (uTAS). The difference, he says, is the emphasis on biolFor tissue-based devices, the reAt the moment, the researchers are ogy. "We're not just miniaturizing searchers trade in the micromachined using only hepatocytes—the dominant wells for miwhat a chemist croscaffolds. would do," he Liver cells, as it explains. 'We're turns out, don't trying to take respond the the best elesame way to toxments of biolins when they ogy and bring are cultured indithem into the vidually as when physical systhey are sxown tems that we as a tissue. In buiid. Perhaps part, that is be•hese devices cause the liver is need a new desa mixture of difignation: micro(a) Closeup of 200
