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Biomolecular Contrast Agents for Optical Coherence Tomography

Lu, George J. and Chou, Li-dek and Malounda, Dina and Patel, Amit K. and Welsbie, Derek S. and Chao, Daniel L. and Ramalingam, Tirunelveli and Shapiro, Mikhail G. (2019) Biomolecular Contrast Agents for Optical Coherence Tomography. . (Unpublished)

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Optical coherence tomography (OCT) has gained wide adoption in biological and medical imaging due to its exceptional tissue penetration, 3D imaging speed and rich contrast. However, OCT plays a relatively small role in molecular and cellular imaging due to the lack of suitable biomolecular contrast agents. In particular, while the green fluorescent protein has provided revolutionary capabilities to fluorescence microscopy by connecting it to cellular functions such as gene expression, no equivalent reporter gene is currently available for OCT. Here we introduce gas vesicles, a unique class of naturally evolved gas-filled protein nanostructures, as the first genetically encodable OCT contrast agents. The differential refractive index of their gas compartments relative to surrounding aqueous tissue and their nanoscale motion enables gas vesicles to be detected by static and dynamic OCT at picomolar concentrations. Furthermore, the OCT contrast of gas vesicles can be selectively erased in situ with ultrasound, allowing unambiguous assignment of their location. In addition, gas vesicle clustering modulates their temporal signal, enabling the design of dynamic biosensors. We demonstrate the use of gas vesicles as reporter genes in bacterial colonies and as purified contrast agents in vivo in the mouse retina. Our results expand the utility of OCT as a unique photonic modality to image a wider variety of cellular and molecular processes.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Lu, George J.0000-0002-4689-9686
Shapiro, Mikhail G.0000-0002-0291-4215
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. The authors thank Changhuei Yang for helpful discussion and Theodore Chang for assistance with initial experiments. Electron microscopy was performed at the Beckman Institute Resource Centre for Transmission Electron Microscopy at Caltech. This research was supported by the National Institutes of Health (grant numbers K99EB024600 to G.J.L.; K12EY024225 and P30EY022589 to D.L.C.; R44HL129496, R43HD071701 and R44CA177064 to T. R.; R01EB018975 to M.G.S.), the Defense Advanced Research Projects Agency (HR0011-17-2-0037 to M.G.S.), the Heritage Medical Research Institute (M.G.S.), the Packard Fellowship for Science and Engineering (M.G.S.), the Pew Scholarship in Biomedical Science (M.G.S.) and the Burroughs Welcome Fund Career Award at the Scientific Interface (M.G.S.). AUTHOR CONTRIBUTIONS: G.J.L., M.G.S., T.R. and D.L.C. conceived the research. G.J.L., M.G.S., T.R., L.C. and D.M. planned and performed the in vitro experiments, and G.J.L. and L.C. analyzed the data. D.L.C, A.K.P. and D.S.W. planned and performed the in vivo experiments using materials prepared by G.J.L. and D.M.. G.J.L. and M.G.S. wrote the manuscript with input from all authors. DATA AND MATERIALS AVAILABILITY: Raw data, gas vesicles and genetic constructs are available upon request to the authors. The authors declare no competing financial interests.
Group:Heritage Medical Research Institute
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0037
Heritage Medical Research InstituteUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
Pew Charitable TrustUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
Record Number:CaltechAUTHORS:20190401-103122114
Persistent URL:
Official Citation:Biomolecular Contrast Agents for Optical Coherence Tomography George J Lu, Li-dek Chou, Dina Malounda, Amit K Patel, Derek S Welsbie, Daniel L Chao, Tirunelveli Ramalingam, Mikhail G Shapiro bioRxiv 595157; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94314
Deposited By: George Porter
Deposited On:01 Apr 2019 17:49
Last Modified:01 Apr 2019 17:49

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