Electrical Microarrays: Going for the Gold

Courtesy of FRIZ Biochem A microarray substrate and reader for EDDA technology A small German biotechnology company is literally going for the gold in the burgeoning market for DNA microarray systems. FRIZ Biochem of Munich is developing two new electrochemical DNA microarray readout products that will use gold-coated chips for analyzing batches of genes. Simpler to use and less expensive than state-of-the-art fluorescent technology, the systems could be a boon for small to medium-sized research and development laboratories currently priced out of microarray research. The new electrochemical technology is also more sensitive to mismatches and can identify single nucleotide polymorphisms. Both new systems use changes in conductivity to detect gene targets. The first, EDDA (electrically detected displacement assay), will be available by the end of 2003, according to FRIZ Biochem CFO/CTO Harrald Lossau, while the second, LADER (light-induced direct electrically read), is past the proof-of-concept stage. Lossau projects the systems will cost between $10,000 and $30,000 (US)--as little as a tenth of the cost of high-density fluorescent systems. The chips will be priced at about $100 to start, but that could come down if demand justifies high-volume production. "The material cost is negligible even though it's gold," Lossau says, explaining that the gold preparation, used for conductivity and optimal anchoring of probes, is spread only about 200 nanometers deep on top of plastic or glass. He adds that the manufacturing process is also less expensive than producing the optical quality required in glass chips used for fluorescent microarrays. SYSTEM PRIMER EDDA, says Lossau, is slightly more sensitive than current fluorescent methods. Oligonucleotides positioned on an electrode array loosely associate with electrolabel signaling probes. As the chip is interrogated, the presence of these signaling probes can be detected. If, however, the oligonucleotide hybridizes to its complement, the signaling probe will be displaced, causing a significant decrease in the electrochemical readout. LADER uses differences in conductivity between "isolating" single-stranded DNA and "conducting" double-stranded DNA. In LADER, capture probes are connected to an electrode and an electron donor/acceptor (D/A) complex is added, followed by a dissolved active component to create a molecular electrical circuit. Incident light induces a transfer of charge from D to A, but the charge continues on to an electrode only in the presence of hybridization. The LADER process has many of the advantages of EDDA, plus it is more sensitive and could dispense with PCR amplification steps, according to Lossau. Both microarrays hold up to 2,000 features per square centimeter of active surface. The company claims the chips are optimized to achieve "almost 100% hybridization efficiency at high reproducibility." Neither EDDA nor LADER is likely to replace the leading high-density GeneChip produced by Affymetrix of Santa Clara, Calif. The GeneChip is "the Rolls Royce of the DNA chip," Lossau concedes, foreseeing more of a complementary role for the gold chips. For example, a researcher seeking to identify a drug target might use a high-density chip to screen hundreds of thousands of genes. Once 100 candidates are selected, further testing could be easier and more cost-effective with low- to medium-density chips. "Someone who wants to analyze the whole human genome would use Affymetrix," Lossau says. "If the same person only wants to analyze 100 of 100,000 genes, then our system is the system to use." Though he also predicts fluorescence will continue to out-perform electrochemistry in high-density analysis, Wolfgang Schuhmann, a professor in analytical chemistry at the Ruhr- Universität Bochum in Germany, calls the EDDA system "really neat." Besides the cost, he cites the fact that neither EDDA nor LADER requires the user to label target nucleic acids. "One cannot always assume the labeling is not changing the affinity to the complementary system," he says. EDDA, in contrast, "is a totally label-free system." Though LADER is the more sensitive approach, Schuhmann predicts that it also will be more difficult to develop than EDDA. Lossau says the company's ultimate goal is to find a partner and gain US Food and Drug Administration approval to mass market its chips as a diagnostic tool for use in physician's offices. This is the Holy Grail of personalized medicine: A physician would test a patient's DNA to determine whether the individual has a genetic feature targeted by a specific therapy. --Jane Salodof MacNeil function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

Electrical Microarrays: Going for the Gold

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