SBIR Phase I: Microwell Array Plates for Dual-Mode Screening of Bead Libraries

This Small Business Innovation Research (SBIR) Phase I project aims to develop the first-in-class microwell array plates for dual optical and MS imaging of bead libraries comprising up to one million members. As a cost-effective alternative to the traditional flow cytometry-based screening, optical imaging of planar bead arrays has the potential to become a preferred method of analysis in a variety of multiplexed bead-based bioassays. The preliminary experimental data shows that the beads arrayed on optically transparent glass microchips also can be measured with high sensitivity by MALDI TOF MS. The microchips evaluated in this project will be fabricated from fused optic fibers, micro-structured glass and thermoplastics to determine the optimal supports. The unique 3D structure of the microwells will be utilized to perform highly specific elution of selected compounds from individual beads and their localization in tightly focused microspots near the surface of the microwell plate. Fluorescence imaging performed at varying focus distance will provide quantitative detection of the bead-bound and eluted analytes while the mass spec imaging will enable structural characterization of the eluted compounds. The broader impact/commercial potential of this project, if successful, will be the availability of microchips with dual optical and mass spec readout that will facilitate development of new methods of high-throughput screening (HTS), and enable the use of mass spectrometry in various HTS-based applications. Such ability will be particularly important in the field of biomarker discovery given the need for detailed characterization of proteomic biomarkers including identification of the protein sequence variants. This technology also will significantly benefit the field of drug discovery, which relies heavily on the HTS assays. The high-resolution microarray scanning techniques that will be developed in the course of this project are expected to make significant contribution to the rapidly growing field of mass spectrometry imaging, which so far has been focused primarily on measuring distribution of various analytes within biological tissues. Overall, the proposed work will accelerate progress toward a single analytical platform that seamlessly integrates fluorescence and mass spectrometry for the analysis of diverse libraries of microbeads including peptide, protein and antibody bead arrays.