Award Abstract # 1444240
EAGER: Mobile-phone based single molecule imaging of DNA and length quantification to analyze copy-number variations in genome

NSF Org: CBET
Division of Chemical, Bioengineering, Environmental, and Transport Systems
Recipient: UNIVERSITY OF CALIFORNIA, LOS ANGELES
Initial Amendment Date: June 13, 2014
Latest Amendment Date: June 13, 2014
Award Number: 1444240
Award Instrument: Standard Grant
Program Manager: Leon Esterowitz
CBET
 Division of Chemical, Bioengineering, Environmental, and Transport Systems
ENG
 Directorate for Engineering
Start Date: October 1, 2014
End Date: September 30, 2016 (Estimated)
Total Intended Award Amount: $299,995.00
Total Awarded Amount to Date: $299,995.00
Funds Obligated to Date: FY 2014 = $299,995.00
History of Investigator:
  • Aydogan Ozcan (Principal Investigator)
    ozcan@ee.ucla.edu
Recipient Sponsored Research Office: University of California-Los Angeles
10889 WILSHIRE BLVD STE 700
LOS ANGELES
CA  US  90024-4200
(310)794-0102
Sponsor Congressional District: 36
Primary Place of Performance: University of California-Los Angeles
Engineering IV Building
Los Angeles
CA  US  90095-2000
Primary Place of Performance
Congressional District:
36
Unique Entity Identifier (UEI): RN64EPNH8JC6
Parent UEI:
NSF Program(s): EFRI Research Projects
Primary Program Source: 01001415DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 005E, 7916
Program Element Code(s): 763300
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

PI: Ozcan, Aydogan
Institution: University of California-Los Angeles
Proposal number: 1444240
Title: EAGER: Mobile-phone based single molecule imaging of DNA and length quantification to analyze copy-number variations in genome

The aim of this proposal is to create a transformative fluorescent microscopy system that is integrated with next generation mobile-phones for imaging single DNA molecules. This field-portable imaging interface running on a smartphone will have the sensitivity and contrast to image single molecule DNA fragments over a large field of view. Demonstrating DNA imaging on a state-of-the-art mobile-phone would serve as a stepping stone to next-generation mobile micro-analysis, sensing and diagnostic tools and could lead to single molecule DNA sequencing on a smartphone.

The proposed design will have the capability to be broadly used in various clinical applications including early detection of cancers (e.g. stomach and brain), nervous system disorders and drug resistance in infectious diseases. This cellphone based single molecule imaging, DNA platform could also assist health-care professionals, epidemiologists and policy makers to track emerging trends and shed more light on cause-effect relationships.

Intellectual Description:
Single molecule imaging and DNA length quantification, both of which are currently not feasible using mobile-phone based imaging systems; require extreme detection sensitivity, signal-to-noise ratio (SNR), spatial resolution and automated sample handling and processing interfaces. To provide a transformative solution to these important tasks, the PI will design a multifunctional portable imaging device installed on a smartphone which will allow sample preparation and single molecule imaging within the same opto-mechanical attachment. This fluorescence microscope on a smartphone will be designed by integrating a laser diode, a disposable nano-channel chip, an external lens and a thin-film based emission filter in a robust attachment created by 3D printing techniques. High SNR fluorescence signal detection will be achieved by implementing high-angle/oblique illumination so that the direct excitation beam will not enter the low NA collection lens. They will also develop a compressive sampling based DNA length-estimation method which will utilize (i) the measured point spread function of the fluorescent microscope on the mobile-phone; (ii) the spatial sparsity of the objects (fluorescently labeled DNA molecules); and (iii) the linearity of the stretched DNA molecules within the field of view as a-priori constraints to estimate the length of the DNA fragment of interest with an accuracy that is significantly better than the resolution of their initial imaging system.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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(Showing: 1 - 10 of 13)
A. Ozcan "Computational Microscopy, Sensing and Diagnostics (Keynote Talk)" IEEE International Conference on Computational Photography (ICCP), Northwestern University, May 13-15, 2016, Evanston, IL , 2016
A. Ozcan "Democratization of Next-Generation Imaging, Sensing and Diagnostics Tools (Keynote Talk)" Lab-on-a-Chip & Microfluidics Conference, Select Biosciences Meeting, March 16, 2016, Madrid, Spain , 2016
A. Ozcan "Democratization of Next-Generation Imaging, Sensing and Diagnostics Tools Through Computational Photonics (Invited Talk)" OSA Frontiers in Optics (FiO) Conference (October 18-22, 2015), San Jose, California, USA , 2015
A. Ozcan "Democratization of Next-Generation Microscopy, Sensing and Diagnostics Tools through Computational Photonics (Ernst Abbe Lecture)" International Conference on Applied Optics and Photonics (organized by ICO and DGaO), May 19, 2016, Hannover, Germany , 2016
A. Ozcan "Democratization of Next-Generation Microscopy, Sensing and Diagnostics Tools through Computational Photonics (Keynote Talk)" The Annual Meeting of The Federation of Analytical Chemistry and Spectroscopy Societies (FACSS) ? SciX Conference, September 18-23, 2016, Minneapolis, Minnesota , 2016
A. Ozcan "Democratization of Next-Generation Microscopy, Sensing and Diagnostics Tools through Computational Photonics (Plenary Talk)" National Meeting of Electromagnetism, University of Parma, September 12-14, 2016, Parma, Italy , 2016
A. Ozcan "Mobile Imaging, Sensing and Diagnostics (Plenary Talk)" 26th Anniversary World Congress on Biosensors (Biosensors Congress, Elsevier), May 25-27, 2016, Gothenburg, Sweden , 2016
E. McLeod and A. Ozcan "Unconventional methods of imaging: computational microscopy and compact implementations" Reports on Progress in Physics , 2016 10.1088/0034-4885/79/7/076001
E. McLeod, Q. Wei and A. Ozcan "Democratization of Nanoscale Imaging and Sensing Tools using Photonics" Analytical Chemistry , 2015 10.1021/acs.analchem.5b01381
J.C. Contreras-Naranjo, Q. Wei, and A. Ozcan "Mobile Phone Based Microscopy, Sensing, and Diagnostics" IEEE Journal of Selected Topics in Quantum Electronics , 2016 10.1109/JSTQE.2015.2478657
Q. Wei, W. Luo, S. Chiang, T. Kappel, C. Mejia, D. Tseng, R. Chan, E. Yan, H. Qi, F. Shabbir, H. Ozkan, S. Feng, and A. Ozcan "Imaging and Sizing of Single DNA Molecules on a Mobile-Phone" ACS Nano , 2015 DOI: 10.1021/nn505821y
(Showing: 1 - 10 of 13)

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.

DNA imaging techniques using optical microscopy have found numerous applications in biology, chemistry and physics and are based on relatively expensive, bulky and complicated set-ups that limit their use to advanced laboratory settings. In this proposal timeline, we demonstrated imaging and length quantification of single molecule DNA strands using a compact, light-weight and cost-effective fluorescence microscope installed on a mobile-phone (see the Figures). In addition to an opto-mechanical attachment that creates a high contrast dark-field imaging set-up using an external lens, thin-film interference filters, a miniature alignment stage and a laser-diode for oblique-angle excitation, we also created a computational framework and a mobile-phone application that is wirelessly connected to a server for the measurement of the lengths of individual DNA molecules that are labeled and stretched using disposable chips. Using this mobile-phone platform, we imaged single DNA molecules of various lengths to demonstrate a sizing accuracy of <1 kilobase-pairs (kbp) for 10 kbp and longer DNA samples imaged over a large sample field-of-view of ~2 mm2.

Through these results, we demonstrated a new milestone for cellphone based microscopy and sensing tools by single molecule fluorescent imaging and detection of DNA fragments using disposable chips. Until our recent results, this performance was out of reach for existing mobile-phone based imaging techniques, and will serve as the stepping stone to next-generation mobile micro-analysis, sensing and diagnostic tools and might also lead to single molecule DNA sequencing using mobile-phones. Furthermore, the same single molecule fluorescent imaging platform also permitted the accurate quantification of DNA length, which can be used for determining copy-number variations in genome through a field-portable and cost-effective mobile device – a capability that can be broadly used in various clinical applications including early detection of cancers (e.g., stomach, brain cancer etc.), nervous system disorders or even drug resistance in infectious diseases, including malaria. The latter is of paramount importance especially for global health problems, and might help us achieve early diagnosis of drug resistant malaria, assisting us to take appropriate measures earlier in the treatment process, potentially saving lives and avoiding waste of resources and medicines. Offering spatio-temporal data mapping, this single molecule DNA imaging and sizing platform could also assist e.g., health-care professionals, epidemiologists and policy makers, among others, to track emerging trends and shed more light on genetic cause-effect relationships in point-of-care and resource limited settings.

These results that we have got will also serve as our stepping stone to new landmarks for mobile imaging and diagnostic tools and their technical capabilities, shaping the future designs and digital components of mobile phones and other consumer electronics devices for use in next generation mobile-health and telemedicine technologies, also significantly impacting the future practices of preventive medicine.

Finally, this proposal also established a complementary educational outreach program which involved (1) public interviews and popular science articles in news media and internet; (2) undergraduate research opportunities in PI’s laboratory involving minority students; and (3) graduate student training through organization of workshops and seminars. Furthermore, research projects, seminars and open house visits served undergrads and high school students (especially from minority groups) to interact with a cutting edge research environment, helping to increase their scientific curiosity and shaping their career goals in science and engineering.


Last Modified: 12/21/2016
Modified by: Aydogan Ozcan

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