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Apr 15, 2010 (Vol. 30, No. 8)

Progress a Must for Protein Microarrays

Better Tools and Methodologies Are Needed to Move the Field Past a Critical Stage

  • Biomarker Measurement

    Jim Rusling, Ph.D., professor of chemistry and cell biology at the University of Connecticut, is pursuing the development of arrays for the accurate measurement of cancer biomarker proteins for early cancer detection, surgical applications, and cancer monitoring. At present, researchers in Dr. Rusling’s lab are working on various approaches that can do this in an ultrasensitive fashion.

    In one of those methodologies, Dr. Rusling uses nanostructured sensor surfaces as a basis for immunosensor arrays. The nanostructured surfaces could contain carbon nanotubes or tiny gold nanoparticles, and they have chemistry that allows the user to attach antibodies to the cancer biomarkers.

    “The antibodies capture the protein of interest from the sample, and then we come in with a labeled secondary antibody that is attached to a multiple enzyme-labeled nanoparticle,” he explained. “We are also interfacing these arrrays with microfluidics for automated use.”

    Dr. Rusling has reportedly been able to achieve extremely good sensitivity and detection limits. “We hope that the devices will be used in doctors’ offices and clinics for screening patients.”

  • New Tools

    With regard to new array design tools, PEPperPRINT has developed a new biochip platform with which customized high-density peptide microarrays can be generated at reasonable costs, said Volker Stadler, Ph.D., CEO.

    To create these arrays, PEPperPRINT employed xerography—a method in which the company “prints amino acid toners by means of a 20-color printer on conventional glass slides.” Melting these toner particles releases the embedded amino acids for high-density combinatorial peptide synthesis, he noted.

    Dr. Stadler will talk about xerography  at the Select Biosciences’ meeting. He will cover the basics of this new approach and present case studies that demonstrate the usefulness of peptide microarrays generated. “These case studies cover different applications from epitope mapping and antibody profiling up to the identification of new and unnatural target binders and maybe also some enzymatic assays.”

    Larry Gold, Ph.D., CEO and chairman of the board at SomaLogic, will present data on a new class of reagents called SOMAmers at the Select Biosciences meeting. Created using a form of DNA, SOMAmers “are effectively super-monoclonals that allow one to bind to proteins in plasma and serum with nearly absolute specificity,” Dr. Gold reported.

    The reagents were developed with the aim of eliminating the problem of high noise that is intrinsic to the use of monoclonal antibodies in array-based detection and were used to build a protein microarray for biomarker discovery.

    SomaLogic’s array is essentially the result of learning from the mistakes of past attempts at developing protein arrays. The assay increases the specificity of array-based protein detection by decreasing binding avidity (by performing all binding reactions in solution rather than on printed slides), Dr. Gold added.

    “Finally, at the end of the assay, because SOMAmers are made out of DNA, they can be quantified on a DNA chip—in fact we quantify proteins by measuring the SOMAmers that are bound specifically to each protein.”

    Dr. Gold’s presentation will focus on the absolute specificity and high precision of these arrays as tools for protein biomarker identification and quantification, as well as show clinical data that demonstrates the array as a potential diagnostic assay for non-small-cell lung cancer. 

    When it comes to biomarker development, researchers have not even begun to scratch the surface, especially when trying to predict disease. “Using a single biomarker, the statistics of cancer prediction success are not very good. So the advantage of having an array and measuring a number of biomarkers, which could be as little as four or as many as 20, is that the statistics of prediction goes way up. And some people say that, if we are able to do this, cancer prediction may reach 100 percent. That means the reliability of your screening process will be much improved compared to current use of a single biomarker,” Dr. Gold said.

    Microarray development is a relatively new science, with much of the information known for DNA arrays and protein arrays trying to play catch-up. The work being done in the field will likely bring protein arrays closer to realizing their full potential.

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