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Award Abstract # 1149015
CAREER: DNA Analysis Based on Dielectrophoresis

NSF Org: CBET
Division of Chemical, Bioengineering, Environmental, and Transport Systems
Recipient: ARIZONA STATE UNIVERSITY
Initial Amendment Date: April 14, 2012
Latest Amendment Date: July 31, 2014
Award Number: 1149015
Award Instrument: Standard Grant
Program Manager: Christina Payne
cpayne@nsf.gov
 (703)292-2895
CBET
 Division of Chemical, Bioengineering, Environmental, and Transport Systems
ENG
 Directorate for Engineering
Start Date: April 15, 2012
End Date: September 30, 2018 (Estimated)
Total Intended Award Amount: $494,028.00
Total Awarded Amount to Date: $513,936.00
Funds Obligated to Date: FY 2012 = $494,028.00
FY 2014 = $19,908.00
History of Investigator:
  • Alexandra Ros (Principal Investigator)
    Alexandra.Ros@asu.edu
Recipient Sponsored Research Office: Arizona State University
660 S MILL AVENUE STE 204
TEMPE
AZ  US  85281-3670
(480)965-5479
Sponsor Congressional District: 04
Primary Place of Performance: Arizona State University
Box 871604
Tempe
AZ  US  85287-1604
Primary Place of Performance
Congressional District:
04
Unique Entity Identifier (UEI): NTLHJXM55KZ6
Parent UEI:
NSF Program(s): Interfacial Engineering Progra,
Chemical Measurement & Imaging,
Other Global Learning & Trng
Primary Program Source: 01001213DB NSF RESEARCH & RELATED ACTIVIT
01001415DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 007E, 053E, 1045, 5936, 9102
Program Element Code(s): 141700, 688000, 773100
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

1149015 - Ros

The increasing complexity of current analytical challenges demands novel and efficient separation and purification techniques. For example, analyzing a large variety of biomolecules requires powerful separation and purification techniques, and these are often the limiting component in biochemical research such as in biomarker discovery, clinical diagnosis or single cell analysis. The separation and purification of novel macromolecular structures such as artificial DNA nano-assemblies is further essential for their successful nano-technological applications, such as for DNA computing, in photonic devices or in targeted diagnostics.

This proposal supported by the Chemical and Biological Separations Program of the Chemical, Bioengineering, Environmental and Transport Systems Division and the Chemical Measurement and Imaging Program of the Chemistry Division supports aims in the study of dielectrophoresis (DEP) of DNA and its application for concentrating, fractionating and separating DNA. The phenomenon dielectrophoresis refers to the migration of polarizable molecules in inhomogeneous electric fields. Variations in the polarization of different DNA species will lead to differences in migration, which can be exploited for analytical purposes. To date however, the polarization mechanism of DNA remains only little understood, which hampers the use of dielectrophoresis for analytical applications. This proposal thus aims at a quantitative study of the polarizability for a wide variety of DNA not only allowing the application of dielectrophoresis for separation and pre-concentration but also to reveal the origin of DNA polarizability. A tailored miniaturized platform employing insulator-based DEP will be used to establish the necessary electric field conditions for DEP to occur. The employed microfluidic platforms further provide miniaturized and fast analysis of DNA by DEP, and will allow the analysis of minute samples in the range of pico- to nano-liters suitable for the analysis of DNA in small cell ensembles or even single cells. Concomitantly occurring transport mechanisms for DNA will be investigated to reveal their interplay with DNA DEP with the ultimate goal to optimize DNA analysis. Based on this knowledge, analytical applications ranging from DNA nanotechnology over quality control of DNA vaccines to DNA-based diagnostics are proposed.

This project also proposes a mentoring plan for female undergraduate and graduate chemistry students in the Chemistry and Biochemistry Department at ASU. The proposed activities aim in encouragement and promotion of women, which are still underrepresented in chemistry at higher career stages. The plan includes individual mentoring activities as well as general activities for female undergraduate students including research opportunities related to the intellectual merit of this proposal. At the graduate level, the plan specifically intensifies these mentoring activities to ameliorate communication, scientific presentation and negotiation skills as well as networking opportunities, PhD progress and career development.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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D. Kim, M. Sonker, A. Ros "Dielectrophoresis: From Molecular to Micrometer-Scale Analytes" Analytical Chemistry , 2018 10.1021/acs.analchem.8b05454
F. Camacho Alanis, L. Gan, A. Ros "Transitioning streaming to trapping in DC insulator-based dielectrophoresis forbiomolecules" Sensors and Actuators B: Chemical , v.173 , 2012 , p.668-675 10.1016/j.snb.2012.07.080
Lin Gan, Fernanda Camacho-Alanis, Alexandra Ros "Polarizability of six-helix bundle and triangle DNA origami and their escape characteristics from a dielectrophoretic trap" Analytical Chemistry , v.12059-1 , 2015 , p.12059 10.1021/acs.analchem.5b02524
Lin GanTzu-Chiao ChaoFernanda Camacho-AlanisAlexandra Ros "Six-Helix Bundle and Triangle Origami Insulator-Based Dielectrophoresis" Analytical Chemistry , v.85 , 2013 , p.11427 10.1021/ac402493u
M. T. Rabbani, C. F. Schmidt, A. Ros "Single-Walled Carbon Nanotubes Probed with Insulator-Based Dielectrophoresis" Analytical Chemistry , v.89 , 2017 , p.13235 10.1021/acs.analchem.7b03105
P.V. Jones, G. L. Salmon, A. Ros "Continuous Separation of DNA Molecules by Size Using Insulator- Based Dielectrophoresis" Analytical Chemistry , v.89 , 2017 , p.1531 10.1021/acs.analchem.6b03369

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

The increasing complexity of current analytical challenges demands novel and efficient separation and purification techniques. For example, the elucidation of molecular level biological complexity requires powerful separation and purification techniques, and is often the limiting component in biochemical research such as in biomarker discovery, clinical diagnosis, or single cell analysis. The separation and purification of novel macromolecular structures such as artificial DNA and nano-assemblies is further essential for their successful nanotechnological applications and it may have impact on the quality control of plasmids for vaccines. Understanding the molecular properties of these novel DNA and nano-assemblies will also facilitate employing them for nanoelectronic circuitry, intelligent sensing or targeted drug delivery. This proposal focused on elucidating a novel separation criterion, namely the dielectrophoretic property of DNA as well as DNA-assemblies and nanoparticles. The knowledge gained in our work will extend the portfolio of techniques analyzing complex mixtures, and our findings may be applicable to other biomolecules or other nanoparticles. We investigated the underlying polarizability of DNA in detail for a variety of DNA species on a microfluidic platform and used the gained insight for analytical applications based on DNA dielectrophoresis (DEP). In addition, we have investigated the dielectrophoretic properties of single walled carbon nanotubes with an emphasis on variations by nanotube length and suspension method, which may have implications on targeted applications of these nanomaterials.

A major goal of the proposal was the characterization of the dielectrophoretic properties of artificial DNA assemblies, such as DNA origami. Microfluidic devices were developed which allowed to study the polarization properties of DNA origami and eventually led to the separation of these species. In addition, microfluidic device designs were altered and optimized to initiate DNA separation including constriction and array sorters based on the principles of dielectrophoresis. We also explored novel nano- and microfluidic environments which could enhance the desired migration properties. The study was supplemented with the development of suitable numerical tools which allowed us to predict and design the desired migration and separations effects. These computational tools will allow us to transfer gained knowledge to other biomolecular entities or nanomaterials in the future.

This project was conducted in collaboration with post docs, graduate students, and undergraduate students. Students and post docs were trained in DNA separation, microfluidics and instrument development as well as handling of nanomaterials. The project also facilitated mentoring for female students in the chemistry field, initiated international collaborations, and allowed students to collaborate internationally. Opportunities were provided for undergraduate and graduate students as well as post docs to present their results at scientific conferences.

 


Last Modified: 12/20/2018
Modified by: Alexandra Ros

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