PhD Proposal: Lisa Bonanno

Investigation of Novel Device Formats to Increase Detection Sensitivity of Porous Silicon Optical Biosensors

Abstract

Large operational costs and long result turn-around time associated with current laboratory-based clinical testing drives the need for developing new innovative diagnostic methods at point of care (POC). Porous silicon (PSi) is an ideal material for biosensing due to its inexpensive fabrication, intrinsic optical and filtering properties, and compatibility with array and microfluidic technologies. These properties of PSi offer advantages over current technologies by its potential for uncomplicated high-throughput analysis at point-of-care (POC). The specific detection of target molecules has been widely demonstrated with the use of PSi biosensors; however, current sensitivity limitations pose restrictions to their use in the diagnosis of the majority of diseases and drug screening assays. The focus of this research will make use of innovative design in sensor format and competitive immunoassay techniques to detect drugs of abuse (morphine, codeine) in urine with unprecedented detection sensitivity. Our long term goal is to exploit PSi for affinity-based optical biosensing to improve patient health care by reducing costs and time associated with diagnostic screening.

The proposed research will first aim to develop and optimize a competitive binding assay in PSi biosensors to enhance detection of a model small molecule target (morphine 3- -D-glucoronide, M3G) in patient urine specimens. This opiate screening assay will serve as a proof of concept and will be the first time that a competitive immunoassay will be used in PSi to screen human patient specimens. The second aim will integrate the competitive PSi immunoassay into a target-responsive hydrogel which will encapsulate a PSi sensor. The proposed design will address physical constraints of current PSi optical sensor techniques, extend probe immobilization throughout the 3D internal volume of the PSi, and exploit the morphological response of the hydrogel with the intention of increasing device sensitivity. This novel design will demonstrate for the first time the ability of PSi to detect both dielectric and morphological changes of the target-responsive hydrogel in response to competitive binding of target molecule. This study will establish rational design criteria for developing PSi optical biosensors and methodologies developed here could be extended to detect multiple targets in clinical applications. One could envision future development of this technology into a dermal sweat patch drug screening method with intrinsic optical sensing capability.