National Science Foundation     |     Directorate for Engineering  (ENG) Division of Chemical, Bioengineering, Environmental, & Transport Systems  (CBET)   CBET Research Highlights  Notable Accomplishments from CBET Awards

7236 - Part A - Lensfree Computational Microscopy Tools for Telemedicine Applications   Aydogan Ozcan  -  University of California-Los Angeles

Outcome or Accomplishment:  Electrical engineering researchers at UCLA have invented new microscopy and imaging techniques that are compact and light-weight enough to be integrated onto cellphones to convert them into cost-effective diagnostic tools.  This new telemedicine platform works based on computation which is used to replace bulky optical components with algorithms.

Figure 1.  A lensfree holographic microscope that is installed at the back of a cellphone is illustrated.  This microscope uses the shadows of objects to reconstructs their microscopic images using computer algorithms.

Figure 2.  Schematic diagram and images of a lensfree reflection microscope are illustrated.

Figure 3.  A field-portable super-resolution microscope is illustrated. This microscope can achieve sub-micron resolution across ~30 mm2.  Images of malaria parasites captured with this lensfree microscope are also shown on the right.   Credit for All Images:  Ozcan Research Group at UCLA

Impact:  The research developed in this award could be quite important for telemedicine applications, by bringing advanced detection and sensing platforms to resource-poor and remote locations.  One example would be screening of infectious diseases such as malaria, TB or HIV, even in field settings.  Apart from telemedicine applications, the same platform can also be used for environmental monitoring needs, by quantifying contamination of water, resources, or air. Explanation/background:  This CAREER award explores how the recent revolutionary progress in digital technologies together with novel image reconstruction algorithms and theories can fundamentally transform the way that we conduct cell microscopy, cytometry and medical diagnostics.  For this end, this award makes a systematic effort to highlight this timely opportunity to revolutionize cell microscopy and cytometry, fields that have been explored for decades, by making them free of any lenses, lasers or other bulky optical elements with a much simpler, compact and cost-effective imaging architecture, while at the same time significantly increasing the imaging throughput, a criterion that is of special interest in cell micro-biology, microfluidics as well as medical diagnostics.   Regarding the results of this award, Dr. Ozcan has given several public lectures on the use of advanced photonics based telemedicine technologies for global health challenges which are now shared in YouTube, Facebook, Twitter and other webpages.  Several articles on Dr. Ozcan's research efforts were also published in e.g., The New York Times, Scientific American, National Geographic, Popular Mechanics, BBC, CNN,USA Today, The Scientist, etc.   Dr. Ozcan's research group also hosted various high school students from Southern California to give tours of various research activities in the lab, which were then followed by a lecture/presentation given by the PI or the graduate students/postdoctoral scholars.   All these activities are also shared with the public using the Group's Facebook page as well as its Twitter and YouTube pages: http://www.facebook.com/pages/The-Ozcan-Research-GroupUCLA/118434778220991 https://twitter.com/#!/InnovateUCLA http://www.youtube.com/user/ozcanresearchgroup   Within the last 2 years, at UCLA Dr. Ozcan also started a new undergraduate course titled Lasers in BioMedicine, which involved a revised curriculum that is centered around BioPhotonics and its impact to Human Health.

CBET Research Highlight - Part B - Engineering Technical Information 7236 - Lensfree Computational Microscopy Tools for Telemedicine Applications Aydogan Ozcan  -  University of California-Los Angeles Background:  Within this proposal timeline, Ozcan Research Group has achieved the following advances in lensfree computational imaging technologies (i.e., LUCAS) and their applications: - 1-  They created the first implementation of lensfree optical tomography.  In this new imaging modality Ozcan Research Group utilized pixel super-resolution techniques with multi-angle illumination to achieve sub-micron lateral and sub-3um axial resolution in optical part of the spectrum.&nbsb; These results were published in PNAS and constitute the first time that lensfree optical imaging achieved depth sectioning. - 2-  Ozcan Group also applied the above discussed lensfree tomographic imaging modality to opto-fluidics such that tomographic imaging of specimens that are flowing within a micro-channel can be achieved without the need for stopping the flow.  These results were published in APL and were also presented in various conferences. - 3-  They created 2 new field-portable microscope designs that can image specimen in both transmission and reflection modes.  This is quite important since some specimens are not transparent which makes it essential to switch to reflection geometry.  These results were published in two different journals (Biomedical Optics Express and Lab on a Chip) and were also presented in various conferences. - 4-  Ozcan research group also implemented opto-fluidics based fluorescent flow-cytometer running on a cellphone. This cost-effective, compact and light-weight attachment to the cellphone enables to screen labeled liquid samples through a flow-chamber that is inserted on the cellphone.  These results were published in Analytical Chemistry and were also presented in different conferences and meetings. - 5-  They also implemented enhanced contrast and signal to noise ratio imaging on a chip using thin wetting films along with pixel super-resolution.  The thin film that forms around each object on a chip acts like a lens, which significantly increased the contrast and SNR of the imaging results.  This new technique that is based on thin wetting-films is published on Optics Express, and was presented in various conferences and meetings. Innovative and Potentially Transformative Research:  The recent revolutionary progress in digital technologies together with novel image reconstruction algorithms and theories can fundamentally transform the way that we conduct cell microscopy, cytometry and medical diagnostics.  With this vision, this proposal makes a systematic effort to highlight this timely opportunity to revolutionize cell microscopy by making it free of any lenses, lasers or other bulky optical components with a much simpler, compact and cost-effective imaging architecture especially suitable for telemedicine needs and requirements.  Through incoherent lensfree cell holography & on-chip microscopy platform of this proposal (i.e., LUCAS), one can compensate in the digital domain for the lack of complexity of optical components by recording individual phase & amplitude holograms of various cell types.  These cell holograms also yield accurate reconstruction of microscopic images featuring sub-cellular resolution over a very large field of view (FOV) even at cell densities reaching up to ~0.4 Million cells/_L.  Merging cost-effective and compact LUCAS imagers with the state-of-the-art cell-phone technology will create numerous opportunities for telemedicine to improve health care especially in the developing world where medical facilities and infrastructure are extremely limited.   Toward these goals, Ozcan Research Group has demonstrated the highest resolution lensfree on-chip microscope to date by using pixel super-resolution in partially coherent in-line holography.  As a result they achieved a numerical aperture of ~0.5 over a very large imaging field of view of ~24-30 mm2.  Furthermore, they have demonstrated the first implementation of lensfree optical tomography to significantly improve the axial resolution of their lensfree images, achieving <3um axial resolution as well as sub-micron lateral resolution.   In addition to these, Ozcan Group has also demonstrated field portable and cost-effective versions of the same super-resolution lensfree microscope as well as the lensfree tomographic microscope that weigh less than 100 and 135 grams, respectively, which can be utilized to image e.g., malaria smears and parasites even in field settings.   Other important contributions of this work over the last 2 years include:  first demonstration of flow-cytometry on a cellphone, first demonstration of a lensfree reflection and transmission dual-mode field microscope, first demonstration of lensfree fluorescent imaging on a chip and first demonstration of lensfree plasmonics sensing on a chip.   These are transformative advances for lensless computational microscopy/imaging to close the gap between conventional microscopy techniques and their lensless alternatives for various applications including telemedicine and high-throughput screening.

Intellectual Merit:  There are several aspects of the proposed platform and the reported results that make them transformative for telemedicine-based cytometry and diagnostics applications in resource-poor settings.  First, the light source in this holographic approach does not need to be a laser, i.e., a spatially incoherent source (such as an LED) can be used without the need for any lenses or other bulky optical components.  This feature greatly simplifies the optical set-up, making it cost-effective and compact.  Second, the presented on-chip holography approach, unlike conventional approaches, does not require a small aperture size for illumination and therefore improves the light throughput of the imaging system by orders-of-magnitude without causing an issue for cell hologram pattern analysis or digital image reconstruction.  This large aperture size (e.g., 50-100 _m) also makes it robust to mechanical misalignments or potential clogging problems, making it highly suitable for point-of-care operation or field use.  Third, it can image a much larger field of view typically by >10-100 fold than a conventional optical microscope or a lensfree holographic microscope, significantly increasing the throughput of imaging.  Fourth, apart from reconstructing microscopic images of cells, it also detects a unique 2D holographic texture (i.e., a fingerprint) corresponding to each cell.  This cell fingerprint provides an alternative source of digital information that complements the reconstructed images for making a diagnostic decision based on pattern matching of healthy vs. diseased cell hologram signatures.  This is an entirely new direction in cell holography which treats the amplitude & phase of cell holograms as fingerprints rather than data to be reconstructed.

Broader Impacts of this research include:   - 1 -  Benefits to society:  The lensfree computational on-chip microscopy platform of this proposal permits orders of magnitude improvement in the cost, size and weight of the imaging and diagnostic instrument, making it highly suitable to be used by minimally trained medical personnel in third world countries.  These research results will create new paradigms in telemedicine, where mobile health-care providers will start to enlarge the coverage span of hospitals in resource poor settings through the use of light-weight and cost-effective LUCAS units for medical diagnostic tests.   To initiate this revolution, within this proposal timeline Ozcan research group has been providing transformative solutions to various global health problems such as malaria and HIV by pioneering novel lensfree digital imaging and diagnostic architectures.  The results of this proposal can also replace automated scanning microscopes found in advanced laboratories for high-throughput cell analysis with much simpler, less costly and easier to use lensfree holographic imagers that at the same time significantly improve the throughput.   - 2 -  Broadening participation of underrepresented groups:  Dr. Ozcan's group hosted various high school students of various ethnicities and gave tours of different research activities in the lab.  This was also often followed by a lecture/presentation given by Dr. Ozcan or the graduate students/postdoctoral scholars.   - 3 -  Advancing discovery and understanding while promoting teaching, training, and learning:  Two graduate and ten undergraduate students were involved in these research projects.  They were trained on experimental skills that involved setting up an optical imaging system and getting images of e.g., cells with that set-up.  These graduate students were also trained on theoretical and numerical aspects of different image reconstruction schemes and their application to holographic, fluorescent lensfree on-chip imaging and cytometry.   - 4 -  Enhancing the infrastructure for research and education:   Several graduate students were trained on nano-fabrication tools and Finite Difference Time Domain (FDTD) simulation tools to design and fabricate plasmonic nano-aperture arrays to sense minute refractive index changes on a chip.  As a result of these activities, several journal and conference papers were published which may have applications in fundamental research and the design of plasmonic nano-arrays.   - 5 -  Results disseminated broadly to enhance scientific and technological understanding:  As for outreach, Dr. Ozcan has given several public lectures on the use of advanced photonics based telemedicine technologies for global health challenges which are now shared in YouTube, Facebook, Twitter and other webpages.  Several articles on PI's research efforts were also published in e.g., The New York Times, Scientific American, National Geographic, Popular Mechanics, BBC, CNN,USA Today, The Scientist, etc.   All of the above activities are also shared with the public using the Group's Facebook page as well as its Twitter and YouTube pages: http://www.facebook.com/pages/The-Ozcan-Research-GroupUCLA/118434778220991 https://twitter.com/#!/InnovateUCLA http://www.youtube.com/user/ozcanresearchgroup

Program Director:		Leon Esterowitz CBET Program Director - Biophotonics
NSF Award Number:		0954482
Award Title:		CAREER: A new Telemedicine Platform using Incoherent Lensfree Cell Holography and Microscopy On a Chip
Principal Investigator:		Aydogan Ozcan
Institution Name:		University of California-Los Angeles
Program Element Code:		7236
CBET Research Highlight:		Fiscal Year 2012
Approved by CBET on:		27 March 2012

Top of Page This CBET Research Highlight was Updated on 15 May 2012.