Methods to enhance the stability and sensitivity of NEMS biosensors

• Author / Creator

  Zheng,Wei

• Mass sensitive mechanical resonator based biosensors are a promising label free biological sensing platform due to the capability for high sensitivity, fast response, accurate and real time measurement, integration with traditional electronics and flexible readout techniques. With the advancement of top down nano fabrication techniques, the dimensions of mechanical resonators scale from the micrometer down to the nanometer scale. Silicon carbonitride (SiCN) nanomechanical string resonator biosensors are advantageous in terms of large array integration, extremely high sensitivity and potential for multiple targets detection. However, there are two bottle-neck issues that have limited this type of biosensors from moving out of research labs and using in clinical applications. First, the biological detection sensitivity is determined by the mass of the string itself. Traditional methods of reducing the size of the strings are limited by lithography. Second, the commonly used surface modification techniques are either chemically unstable on SiCN surfaces or biologically incompatible, which causes instability and unreliability of the biosensing system. In this work, two novel methods have been proposed and implemented to solve these two problems and enhance the performance of this type of biosensors. First, a novel type of porous nanostring has been fabricated to reduce the mass of the string while avoiding the limitations of electron beam lithography (EBL). A helium ion beam was used to perform post-fabrication modification of the nanomechanical resonators. More precisely, arrays of pores were milled by ion beam along the length of glassy nanostrings. This post-fabrication method has the advantage of flexible and precise control over the dimensions, locations and the numbers of the milled patterns while with a high yield. The porous nanostrings had reduced mass and increased surface adsorption area. This method provides an alternative technique to achieve small-mass string and opens a new route to enhance the detection sensitivity of mechanical resonator based biosensors. In order to solve the second problem, diazonium salt reduction induced aryl film grafting was used, for the first time, on the SiCN nanostrings for bio-functionalization. This chemistry provides strong chemical adhesion and long term stability. First, diazonium chemistry was used to modify the surface of bare SiCN chip. The strong interfacial chemical bonding between the aryl film and SiCN surfaces was verified by X-ray photoelectron spectroscopy. Rabbit immunoglobulin G (IgG) sandwich immunoassays, with FITC and AuNP labels respectively, were performed on the modified SiCN surfaces. Scanning electron microscopic and confocal microscopic inspection of the samples showed uniform and dense coverage of the detection target on the samples. After this initial verification, the diazonium chemistry was adopted to bio-functionalize SiCN nanostring arrays. Anti-rabbit IgG and rabbit IgG were respectively immobilized onto diazonium modified nanostrings as probe and target. Immobilization of the probe and target were individually successfully observed by the significant downshifts of mechanical resonant frequencies of the nanostrings. A high resolution helium ion microscope was used to inspect the functionalized nanostrings and further verify the grafting of the analyte molecules on the nanostrings. As a proof of concept, diaznonium chemistry was demonstrated to be an effective modification method to functionalize SiCN nanostring mechanical resonator for its use as biosensor. These strategies enhance the detection sensitivity and stability of nanomechanical biosensors and potentially pave the way for the clinical applications.

• Subjects / Keywords

  • NEMS
  • biosensor
  • hellium ion microscopy
  • e-beam lithograohy
  • diazonium

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3CZ3294V

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.