The future of healthcare is heading towards integrated targeted medicine, with the goal of increasing the quality and efficiency while reducing the costs of healthcare. This requires comprehensive knowledge of cellular process involved in health and disease. While array-based approaches have propelled genomics studies resulting in significant discoveries in cancer, autoimmune diseases etc., however, there is still need for technological innovation in developing improved tools for the proteome-level assessment of biological samples in massively parallel fashion.
To make this vision a reality, I along with my team have been working in collaboration with Prof. Paul Utz’s lab at Stanford to further develop and validate a novel silicon-based peptide array platform for biological applications, technology feasibility for which had its origins in then Intel Labs (CTG). We have perfected and further demonstrated biological utility of this wafer scale, high-density, in-situ peptide array platform made with silicon as a support surface, using maskless photolithography approach to synthesize arrays containing peptides covering disease relevant proteins. The research paper demonstrating proof-of-concept studies for Intel peptide arrays as research tools will be published in the August 19th issue of Nature Medicine. In this paper we describe the use of peptide arrays containing every possible overlapping peptide within a linear protein sequence of a region of a protein, H2B, which has been shown to be associated with the autoimmune disease systemic lupus erythematosus (SLE). We demonstrate the functionality of these peptide arrays using commercial antibodies against H2B, and used these arrays to study autoantibodies in SLE patients with increased disease severity.
While our current approach employs optical detection, the eventual goal is to integrate the peptide arrays with a complementary metal-oxide semiconductor (CMOS) circuit beneath each peptide feature to enable electronic sensing for increased robustness, cost effectiveness, and ease of use. This technology has the potential to transform the field by allowing for real-time electronic measurements and computations, which are not possible with current approaches. We have leveraged (already demonstrated by pioneers in case of photolithography based DNA microarrays on glass surfaces) mature semiconductor fabrication technology to create silicon based peptide array platform for protein analysis; to potentially enable detection and analysis of multiplex interactions in real time and enable large scale proteomic studies which have been elusive so far.
Use of these chips for example, could aid clinical research and if developed for detection of serum biomarkers, could rival pharmacogenetic analyses to define subsets of patients who would best respond to therapeutic agents. Peptide arrays platform being agnostics can enable wide range of proteomic applications for epidemiology and population studies beyond medicine, such as agriculture & animal husbandry, bio-defense, food & beverage testing, monitoring of ecology and environmental parameters.