High contrast probe cleavage detection on porous silicon biosensors via quantum dot labeled DNA probes

Using porous silicon (PSi) interferometer sensors, we show the first experimental implementation of the high contrast probe cleavage detection (HCPCD) mechanism. HCPCD makes use of dramatic optical signal amplification caused by cleavage of high-contrast nanoparticle labels on probes instead of the capture of low-index biological molecules. An approximately 2 nm reflectance peak shift was detected after cleavage of DNA-quantum dot probes from the PSi surface via exposure to a 12.5 nM DNase enzyme solution for 2 hrs. This signal change is 20 times greater than the resolution of the spectrometer used for the interferometric measurements, and the interferometric measurements agree with the interferometric response predicted by simulations and fluorescence measurements. These proof of principle experiments show a clear path to real-time, highly sensitive and inexpensive point-of-care readout for a broad range of biological diagnostic assays that generate signal via nucleic acid cleavage.