Novel Optical Biosensors: Singular Intensity Amplification and Molecular Trapping Enhancement at Nanoscales

Developing a novel biosensor with high sensitivity and specificity, fast assay time, large target number and low cost is an important goal of the biosensing community [1- 9]. It may fundamentally transform healthcare and catalyze a new high-tech industry. My thesis goal is to develop new low-cost label-free nanotechnologies that can render such sensitive optical sensors practical for POC applications.

I studied various types of nanostructures, including nanocones, nanowedges, nanogaps and nanospheres, and use the singular optical field [10-14] near them to enhance the optical signals from the probes, thus eliminating the need for expensive detectors. All the sensors do not require nanofabrication techniques and can be integrated to a handheld portable platform that is low-cost and easy to use. The specific molecules quantified in my biosensors are microRNAs, whose irregular expression has been linked to several cancer and chronic diseases. To eliminate target labeling, I have integrated a new hairpin oligo probe with switchable fluorescent reporters to these nanostructures.

To reduce assay time, I use dielectrophoresis (DEP) force and electrophoretic force to trap molecules, which drastically speeds up detection process. I have demonstrated detection of a hundred molecules within fifteen minutes by driving molecules into detection region using electrophoretic force. In addition, I integrated a molecule concentrator [6] with cone array sensor and reduced assay time from more than ten hours to less than one hour. I also employ singular electric field at geometric singularities to generate nanodrops for a future massively large (billions) molecular screening platform. I conclude in the final chapter with a discussion on possible improvements and integration issues to realize integrated platforms.