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Integration of a Droplet-Based Microfluidic System and Silicon Nanoribbon FET Sensor
KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics.ORCID iD: 0000-0002-1002-6699
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
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2016 (English)In: Micromachines, ISSN 2072-666X, E-ISSN 2072-666X, Vol. 7, no 8Article in journal (Refereed) Published
Abstract [en]

We present a novel microfluidic system that integrates droplet microfluidics with a silicon nanoribbon field-effect transistor (SiNR FET), and utilize this integrated system to sense differences in pH. The device allows for selective droplet transfer to a continuous water phase, actuated by dielectrophoresis, and subsequent detection of the pH level in the retrieved droplets by SiNR FETs on an electrical sensor chip. The integrated microfluidic system demonstrates a label-free detection method for droplet microfluidics, presenting an alternative to optical fluorescence detection. In this work, we were able to differentiate between droplet trains of one pH-unit difference. The pH-based detection method in our integrated system has the potential to be utilized in the detection of biochemical reactions that induce a pH-shift in the droplets.

Place, publisher, year, edition, pages
MDPI AG , 2016. Vol. 7, no 8
Keyword [en]
NanoFET; silicon nanoribbon; droplet microfluidics; pH measurement
National Category
Nano Technology
Research subject
Information and Communication Technology
Identifiers
URN: urn:nbn:se:kth:diva-191177DOI: 10.3390/mi7080134ISI: 000382467700006Scopus ID: 2-s2.0-84984791952OAI: oai:DiVA.org:kth-191177DiVA: diva2:955309
Funder
Knut and Alice Wallenberg Foundation
Note

QC 20160825

Available from: 2016-08-25 Created: 2016-08-25 Last updated: 2017-11-28Bibliographically 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
2. Droplet Microfluidics reverse transcription and PCR towards Single Cell and Exosome Analysis
Open this publication in new window or tab >>Droplet Microfluidics reverse transcription and PCR towards Single Cell and Exosome Analysis
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Miniaturization of biological analysis is a trend in the field of biotechnology aiming to increase resolution and sensitivity in biological assays. Decreasing the reaction volumes to analyze fewer analytes in each reaction vessel enables the detection of rare analytes in a vast background of more common variants. Droplet microfluidics is a high throughput technology for the generation, manipulation and analysis of picoliter scale water droplets an in immiscible oil. The capacity for high throughput processing of discrete reaction vessels makes droplet microfluidics a valuable tool for miniaturization of biological analysis.

In the first paper, detection methods compatible with droplet microfluidics was expanded to include SiNR FET sensors. An integrated droplet microfluidics SiNR FET sensor device capable of extracting droplet contents, transferring a train of droplets to the SiNR to measure pH was implemented and tested. In paper II, a workflow was developed for scalable and target flexible multiplex droplet PCR using fluorescently color-coded beads for target detection. The workflow was verified for concurrent detection of two microorganisms infecting poultry. The detection panel was increased to multiple targets in one assay by the use of target specific capture probes on color-coded detection beads.   In paper III, droplet microfluidics has been successfully applied to single cell processing, demonstrated in paper III, where reverse transcription was performed on 65000 individually encapsulated mammalian cells. cDNA yield was approximately equivalent for reactions performed in droplets and in microliter scale. This workflow was further developed in paper IV to perform reverse transcription PCR in microfluidic droplets for detection of exosomes based on 18S RNA content. The identification of single exosomes based on RNA content can be further developed to detect specific RNA biomarkers for disease diagnostics.

Droplet microfluidics has great potential for increasing resolution in biological analysis and to become a standard tool in disease diagnostics and clinical research.

 

 

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. 69 p.
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:15
Keyword
Droplet microfluidics, Reverse transcription, Droplet PCR, High Throughput biology, Single cell Analysis, Exosomes
National Category
Other Engineering and Technologies not elsewhere specified
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-216669 (URN)978-91-7729-577-8 (ISBN)
Public defence
2017-11-17, Air & Fire, Tomtebodavägen 23A, Solna, 10:00 (English)
Opponent
Supervisors
Note

QC 20171024

Available from: 2017-10-24 Created: 2017-10-23 Last updated: 2017-10-26Bibliographically approved

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Svahn Andersson, HeleneLinnros, Jan

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