Inverse design of a single-frequency diffractive biosensor based on the reporter cleavage detection mechanism

Abstract

Vertically interrogated porous silicon (PSi) interferometric biosensors have shown high potential for sensing bio-molecules as they combine high detection sensitivity with simplicity of fabrication, functionalization, optical coupling, and interfacing with microfluidic systems. However, most interferometric sensor designs require either broadband or wavelength-tunable light sources as well as wide-angle detection schemes, increasing their complexity and cost for point-of-care biosensing applications. The limit of detection of such sensors is also constrained by the small size and low refractive index of biological molecules, making it hard to detect very low concentrations of pathogens. In this work, we use a large-scale computational "inverse design" technique to demonstrate a single-frequency, fixed-angle PSi-based biosensor, which exploits a recently developed high-contrast reporter cleavage detection (HCCD) technique. The HCCD sensors detect high-index reporter cleavage events instead of low-index target analyte capture events as typical for traditional label-free optical biosensors. We use the inverse design approach to discover an optimal configuration of a PSi biosensor that makes use of the extended achievable range of cleavage-induced PSi effective index variations and can be interrogated at a single frequency and at a fixed angle. The optimized design in the form of a one-dimensional PSi grating exhibits the change in the reflectance up to 55 % at the interrogation angle of 12 degrees and wavelength of 600 nm, which is caused by cleavage of Au nanoparticle reporters initially occupying 2% of the sensor surface area. The maximum possible change in reflectance is predicted to be 222 % (for a two-dimensional freeform design not amenable to fabrication). This demonstration may pave the way for developing new or redesigned conventional interferometric and colorimetric point-of-care biosensor systems in combination with the cleavage-based detection schemes.