Quantitative measurement of affinities and kinetics of various biomolecular interactions such as protein-protein, protein-DNA and receptor-ligand is central to our understanding of basic molecular and cellular functions and is useful for therapeutic evaluation. Here, we describe a laser-scanning quantitative imaging method, referred to as spectral-domain optical coherence phase microscopy, as an optical platform for label-free detection of biomolecular interactions. The instrument is based on a confocal interferometric microscope that enables depth-resolved quantitative phase measurements on sensor surface with high spatial resolution and phase stability. We demonstrate picogram per square millimeter surface mass sensitivity, and show its sensing capability by presenting static and dynamic detection of multiplexed protein microarray as immobilized antigens capture their corresponding antibodies.
Bibliographical noteFunding Information:
This work was supported by grants from National Institute of Health (R01 RR19768, EY14975 to J.F.dB), the U.S. Department of Defense (F4 9620-01-1-0014 to M.S.U.), Army Research Laboratory (W911NF-06-2-0040 to M.S.U.), and the Center for Integration of Medicine and Innovative Technology. The authors are grateful to Drs. Ki Hean Kim and Conor Evans for their contributions to the system setup. C.J. would like to thank the support through Wellman Graduate Fellowship and Hatsopoulous Innovation Award from the MIT Department of Mechanical Engineering.
All Science Journal Classification (ASJC) codes
- Biomedical Engineering