The In-Line-Quadrature BioCD

摘要

The biological compact disc (BioCD) is a sensitive detection platform that detects immobilized biomolecules on the surface of a spinning disc by quadrature laser interferometry. Spinning-disc interferometry (SDI) has the advantage of operating faraway from the 1/f system noise which has a 40 dB per octave slope, thus reducing the detection noise floor by more than 50 dB compared to static interferometric detection techniques. Three quadrature classes of BioCD have been previously reported: micro-diffraction, adaptive optical and phase contrast. In this paper, we introduce a new class of BioCD, the in-line quadrature class, which has achieved a new level of simplicity and sensitivity. A silicon wafer coated by a layer of SiO_2 is used as a substrate for immobilized biomolecules. The thickness of the SiO_2 layer is chosen so that light reflected from the SiO_2 surface on top and the silicon surface below is approximately in phase quadrature. Protein molecules scatter the incident light, adding a phase shift linearly proportional to the mass density of the immobilized protein, which is converted to a far-field intensity shift by quadrature interference. Patterning of protein is achieved by spot printing with a jet printer, which produces protein spots 0.1 mm in diameter. We demonstrate the sensitivity of the in-line quadrature BioCD by an equilibrium dose response experiment on a disc printed with 25,000 proteins spots with a detection limit of 1 ng/mL when divided into 32 virtual wells and treated as 32 separate assays. This current performance is not a fundamental limit, and improvements in disc uniformity will enable scaling up to large numbers of individual assays per disc.