Molecular interferometric imaging.
Common-path in-line shearing interferometry, combined with pixel-array imaging, provides a surface metrology that achieves 15 pm surface height resolution. An eighth-wave thermal oxide on silicon generates a reference wave locked in the condition of phase quadrature for phase-to-intensity conversion that makes surface height or index variations directly detectable by an imaging system. The scaling surface mass sensitivity for the surface metrology application is S(scal) = 7 fg/mm under 40x magnification with a molecular resolution of approximately 12 IgG molecules within a pixel, limited by the surface roughness of the substrate. When applied to reverse-phase immunoassays in an antibody microarray format under 7x magnification, the current limit of detection is 10 ng/ml for 1 hour incubation, limited by biological and chemical variability. The biosensor is compatible with real-time binding measurements under active flow conditions with a binding dynamic range per well of 10(3) and a mass sensitivity of 2 pg/mm(2).
Department of Physics, Purdue University, 525 Northwestern Avenue, West Lafayette, IN 47907, USA.
Ming
M
Zhao
Xuefeng
X
Wang
David D
DD
Nolte
D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D015374:Biosensing Techniques; D004867:Equipment Design; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007074:Immunoglobulin G / Q000737:chemistry; D007368:Interferometry / Q000295:instrumentation* / Q000379:methods*; D008027:Light; D051379:Mice; D055095:Optics and Photonics; D010087:Oxides / Q000737:chemistry; D020543:Proteome / Q000737:chemistry; D011817:Rabbits; D015203:Reproducibility of Results
D000906:Antibodies; D007074:Immunoglobulin G; D010087:Oxides; D020543:Proteome