Silicon Meets Biology

Chips for drug discovery are not new-gene chips, which are microchips containing snippets of DNA, have been in use for a number of years as diagnostic tools or tools to study gene expression. But a few recent initiatives suggest that the combination of silicon and biology can be expanded even further.

A publication in the Aug. 19, 2012 online issue of Nature Medicine highlights a collaboration between researchers at the Stanford University School of Medicine and Intel Corp. to create a peptide chip. In an interesting marriage of wafer fabrication and biochemistry, the researchers were able to synthesize short polypeptide chains directly on the chip, rather than synthesizing the peptides separately and then affixing them to the chip.

In this instance, the chip was designed to detect antibodies recognizing amino acid sequences from a DNA-packaging protein called histone 2B. The chip included every possible overlapping sequence of every length from the last 21 amino acids of the histone 2B protein, and was used successfully to identify lupus patients with high levels of antibodies against histone 2B. In an accompanying press release, the researchers indicate potential uses for the technology in addition to that as a diagnostic tool for lupus. The chip technology could be used to better understand protein-protein interactions or to help design influenza vaccines that elicit a strong immune response.

On a larger scale, the National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency (DARPA) are investing heavily in tissue chips to more accurately detect drug safety signals. Tissue chips are microchips ranging from the size of a quarter to the size of a house key lined with living tissue. The goal is to accurately model the three-dimensional structure and function of human organs, reproducing the complex interactions, both chemical and biomechanical, that occur among different cell types within an organ system. The chips could then be used to predict drug toxicity and efficacy more accurately and at lower cost than current methods.

NIH is providing more than $70 million in funding over 5 years to develop this technology, with part of the funding coming from the recently established National Center for Advancing Translational Science. DARPA is conducting a separate but parallel program. It has awarded two grants, one to the Wyss Institute at Harvard University and the other to MIT, both of which also are NIH tissue chip grant recipients, to develop engineering platforms capable of integrating 10 or more organ systems.