טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentVilensky Mickheev Rita
SubjectDevelopment of Optical Biosensors and their Integration in
Lab-on-a-chip Systems
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisors Professor Ester H. Segal
Professor Moran Bercovici
Full Thesis textFull thesis text - English Version


Abstract

Nanostructured porous silicon (PSi)-based biosensors have been designed and applied for the detection of numerous biological targets (e.g., oligonucleotides, small molecules, proteins and cells) in proof-of-concept laboratory experiments, where straightforward optical detection does not require any secondary label amplification. However, typical detection limits of PSi-based biosensors are in the micro-molar range, limiting its applicability. Thus, methods for enhancing the sensitivity of these sensors are investigated in order to render these simple devices suitable for the detection of biological targets in real-life applications, specifically for diagnostics. Fundamentally, the sensitivity of these optical biosensors is determined by the strength of light-matter interactions. Sensitivity can be enhanced by increasing these interactions, through light confinement mechanisms, by utilizing various sophisticated optical architectures, or by intensifying the frequency of the recognition events. Accordingly, increasing the target concentration by using pre-concentration techniques may significantly improve the performance of the biosensor in terms of sensitivity and response time.

This work presents a multidisciplinary approach towards achieving highly sensitive PSi-based biosensors by interfacing them with electrokinetic pre-concentration technique, isotachophoresis (ITP). We demonstrate this approach for a proof-of-concept detection of DNA. We focus a target DNA within a finite and confined zone using ITP, and deliver this highly concentrated analyte to an on-chip PSi Fabry-Pérot optical transducer, pre-functionalized with capture probes. Using reflective interferometric Fourier Transform Spectroscopy (RIFTS) real-time monitoring, we demonstrate a 1,000-fold improvement in the detection limit, compared to a standard assay which uses the same biosensor. Consequently, we demonstrate a measured limit of detection of 1 nM, without compromising the specificity of the assay. The concepts presented in this work can be readily applied to other ionic target species, paving way for the development of other highly-sensitive chemical and biochemical assay.