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Localized Functionalization and Integration with Microfluidics for Multiplexed Biomolecule Detection using Silicon Nanoribbon-FET Sensors
KTH, School of Information and Communication Technology (ICT).
KTH, School of Biotechnology (BIO).
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Biological processes causing different medical conditions are seldom characterized by the simple presence or absence of a single biomarker molecule and it can be expected that biosensors with options for multiplexed detection of a panel of analytes will be required for the development of bed-side diagnostic/prognostic tools for personalized healthcare. One sensor technology with potential to be used for label-free detection of biomolecules is based on Silicon Nanoribbon Field-Effect Transistors (SiNR FET). In this study, the possibilities for multiplexed detection of biomolecules have been explored by the integration of a SiNR FET device with a microfluidic system, in combination with localized immobilization of receptor molecules using a microdispensing instrument. SiNR FET devices were fabricated using CMOS technology and integrated with a microfluidic delivery system composed of channels defined in an SU-8 layer, covered with a PDMS lid. Switching between buffer solutions of different pH was used to demonstrate that the microfluidic system could be used for controlled sample delivery. The shift in conductance of the sensing wire upon change of pH showed that the SiNR FET devices were functional. Protocols for surface functionalization and biomolecule immobilization were evaluated using model systems based on synthetic complementary DNA oligonucleotides and the protein A-derived Z domain and its interaction with immunoglobulin G. The study demonstrates that localized immobilization of biomolecules on silicon nanoribbons can be achieved, opening up for multiplexed detection of analytes and improved possibilities for referencing.

National Category
Engineering and Technology
Research subject
Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-191181OAI: oai:DiVA.org:kth-191181DiVA: diva2:955311
Funder
Knut and Alice Wallenberg Foundation
Note

QC 20160825

Available from: 2016-08-25 Created: 2016-08-25 Last updated: 2016-08-25Bibliographically approved
In thesis
1. Silicon Nanoribbon FET Sensors: Fabrication, Surface Modification and Microfluidic Integration
Open this publication in new window or tab >>Silicon Nanoribbon FET Sensors: Fabrication, Surface Modification and Microfluidic Integration
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Over the past decade, the field of medical diagnostics has seen an incredible amount of research towards the integration of one-dimensional nanostructures such as carbon nanotubes, metallic and semiconducting nanowires and nanoribbons for a variety of bio-applications. Among the mentioned one-dimensional structures, silicon nanoribbon (SiNR) field-effect transistors (FET) as electro-chemical nanosensors hold particular promise for label-free, real-time and sensitive detection of biomolecules using affinity-based detection. In SiNR FET sensors, electrical transport is primarily along the nanoribbon axis in a thin sheet (< 30 nm) serving as the channel. High sensitivity is achieved because of the large surface-to-volume ratio which allows analytes to bind anywhere along the NR affecting the entire conductivity by their surface charge. Unfortunately, sensitivity without selectivity is still an ongoing issue and this thesis aims at addressing the detection challenges and further proposing effective developments, such as parallel and multiple detection through using individually functionalized SiNRs.We present here a comprehensive study on design, fabrication, operation and device performance parameters for the next generation of SiNR FET sensors towards multiplexed, label-free detection of biomolecules using an on-chip microfluidic layer which is based on a highly cross-linked epoxy. We first study the sensitivity of different NR dimensions followed by analysis of the drift and hysteresis effects. We have also addressed two types of gate oxides (namely SiO2 and Al2O3) which are commonly used in standard CMOS fabrication of ISFETs (Ion sensitive FET). Not only have we studied and compared the hysteresis and response-time effects in the mentioned two types of oxides but we have also suggested a new integrated on-chip reference nanoribbon/microfluidics combination to monitor the long-term drift in the SiNR FET nanosensors. Our results show that compared to Al2O3, silicon-oxide gated SiNR FET sensors show high hysteresis and slow-response which limit their performance only to background electrolytes with low ionic strength. Al2O3 on the other hand proves more promising as the gate-oxide of choice for use in nanosensors. We have also illustrated that the new integrated sensor NR/Reference NR can be utilized for real-time monitoring of the above studied sources of error during pH-sensing. Furthermore, we have introduced a new surface silanization (using 3-aminopropyltriethoxysilane) method utilizing microwave-assisted heating which compared to conventional heating, yields an amino-terminated monolayer with high surface coverage on the oxide surface of the nanoribbons. A highly uniform and dense monolayer not only reduces the pH sensitivity of the bare-silicon oxide surface in a physiological media but also allows for more receptors to be immobilized on the surface. Protocols for surface functionalization and biomolecule immobilization were evaluated using model systems. Selective spotting of receptor molecules can be used to achieve localized functionalization of individual SiNRs, opening up opportunities for multiplexed detection of analytes.Additionally, we present here a novel approach by integrating droplet-based microfluidics with the SiNR FET sensors. Using the new system we are able to successfully detect trains of droplets with various pH values. The integrated system enables a wide range of label-free biochemical and macromolecule sensing applications based on detection of biological events such as enzyme-substrate interactions within the droplets.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2016. 82 p.
Series
TRITA-ICT, 2016:22
National Category
Nano Technology
Research subject
Information and Communication Technology
Identifiers
urn:nbn:se:kth:diva-191178 (URN)978-91-7729-075-9 (ISBN)
Public defence
2016-09-29, Sal A, Electrum, Kungl Tekniska högskolan, Kistagången 16, Kista, 10:00 (English)
Opponent
Supervisors
Funder
Knut and Alice Wallenberg Foundation
Note

QC 20160825

Available from: 2016-08-25 Created: 2016-08-25 Last updated: 2016-09-19Bibliographically approved

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