BioCD: Self -referencing interferometer for biosensing

Manoj Varma, Purdue University


The holy-grail of modern medical science is to provide personalized health-care. An individual's state of health can be correlated to the pattern of concentration of several 'marker' molecules, for e.g. the presence of Prostate Specific Antigen (PSA) beyond a certain threshold in the body is a strong indication of prostate cancer. To realize the dream of personalized healthcare, a large number of markers have to be identified and correlated to the state of health across diverse populations. The identified markers have to be quantified subsequently to define an individual's state of health. The technology used to achieve the above should be sensitive, accurate, reliable, high-throughput and should be cheap and simple enough to be able to be available in a clinician's office. Interferometry has been used as a sensitive metrology tool in fields ranging from semiconductor inspection to astronomy. This thesis demonstrates a self-referencing interferometric biosensor (BioCD) with a surface normal design potentially capable of scaling up to thousands of tests per sensor substrates. The sensor concept is similar to an optical CD in that gold microstructures fabricated on the BioCD surface act as wavefront splitting interferometers. In contrast to the optical CD, the BioCD operates in a condition called quadrature, which provides maximum linear response to small phase changes caused by protein binding events. The gold microstructures generate a carrier wave when the BioCD is spun, and protein binding is detected as a modulation of an envelope of the carrier wave pattern created by the immobilized capture proteins. By immobilizing reference and target proteins, differential measurements that automatically subtract out non-specific binding can be obtained. We have demonstrated a detection limit of about 1 ng/ml with this technology, which is a clinically relevant figure for many human and veterinary applications. The specific and non-specific binding signals are separated by 4 orders of magnitude implying that potentially as many simultaneous tests can be performed with a single substrate.




Nolte, Purdue University.

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