Fluorescence / Absorption Spectroscopy, Imaging and Contrast Agents

The development of fluorescence based technology for biomedical sensing has long been an important component of LBRC. Based on either endogenous fluorescence or custom designed quantum dots (QDs) [1], organic dyes or genetically expressed contrast agents, novel imaging and spectroscopic instruments are constructed to tackle pre-clinical and fundamental biological studies. As we push these new technologies to our collaborators, we have succeeded in pursuing a broad range of applications including studies on hepatic diseases [2], DNA repair mechanisms [3], and heme metabolism in malaria infection [4], and intravital monitoring of solid tumor [5] and neuronal plasticity [6]. Some of the more mature technologies have been translated into a clinical setting for diagnostics such as in monitoring middle ear infection [7]. As our collaborators contemplate ambitious scientific studies – such as mapping the whole mouse neuronal connectome or functional monitoring of communication of large neuronal network deep in the mouse brain – LBRC is pulled towards developing the next generation fluorescence techniques, instruments and contrast agents.[8] The current and recent fluorescence technology development projects undertaken in LBRC include:

New Imaging Technologies:

  1. Single-shot 3D imaging via coherent control (PDF)
  2. Structured light 3D cell cytometer (PDF)
  3. Develop IR intravital and whole body imaging setup (PDF)
  4. Next generation multifocal multiphoton microscope (PDF)
  5. Imaging depth extension via structured light (PDF)
  6. Super-resolution imaging via structured light (PDF)

New Spectroscopic Technologies

  1. High throughput wide-field FLIM and PLIM (PDF)
  2. Near-common path Fourier Transform Interferometer (PDF)
  3. Wide-field transient absorption microscopy (PDF)

New Contrast agent development

  1. Design novel IR emitters (PDF)
  2. QD Bio-orthogonal conjugation and targeting (PDF)
  3. Multifunctional super nanoparticles (PDF)

References

  1. Cui, J., A.P. Beyler, L.F. Marshall, O. Chen, D.K. Harris, D.D. Wanger, X. Brokmann, and M.G. Bawendi, Direct probe of spectral inhomogeneity reveals synthetic tunability of singlenanocrystal spectral linewidths. Nat Chem, 2013. 5(7): p. 602-6.
    Franke D, Harris DK, Chen O, Bruns OT, Carr JA, Wilson MWB, Bawendi MG. Continuous injection synthesis of indium arsenide quantum dots emissive in the short-wavelength infrared. Nature Communications. 2016, , 12749. doi: 10.1038/ncomms12749 (2016)
  2. Xu, S., Y. Wang, D.C. Tai, S. Wang, C.L. Cheng, Q. Peng, J. Yan, Y. Chen, J. Sun, X. Liang, Y. Zhu, J.C. Rajapakse, R.E. Welsch, P.T. So, A. Wee, J. Hou, and H. Yu, qFibrosis: a fullyquantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients. J Hepatol, 2014. 61 (2):p. 260-9.
  3. Sukup-Jackson, M.R., O. Kiraly, J.E. Kay, L. Na, E.A. Rowland, K.E. Winther, D.N. Chow, T.Kimoto, T. Matsuguchi, V.S. Jonnalagadda, V.I. Maklakova, V.R. Singh, D.N. Wadduwage, J.Rajapakse, P.T. So, L.S. Collier, and B.P. Engelward, Rosa26-GFP Direct Repeat (RaDRGFP) Mice Reveal Tissue- and Age-Dependence of Homologous Recombination in Mammals In Vivo. PLoS Genet, 2014. 10(6): p. e1004299
  4. Abshire, J.R., C.J. Rowlands, S.M. Ganesan, P.T. So, and J.C. Niles, Quantification of labile heme in live malaria parasites using a genetically encoded biosensor. Proc Natl Acad Sci U S A, 2017.
  5. Han, H.S., E. Niemeyer, Y. Huang, W.S. Kamoun, J.D. Martin, J. Bhaumik, Y. Chen, S. Roberge, J. Cui, M.R. Martin, D. Fukumura, R.K. Jain, M.G. Bawendi, and D.G. Duda, Quantum dot/antibody conjugates for in vivo cytometric imaging in mice. Proc Natl Acad Sci U S A, 2015. 112(5): p. 1350-5
  6. Villa, K.L., K.P. Berry, J. Subramanian, J.W. Cha, W.C. Oh, H.B. Kwon, Y. Kubota, P.T. So, and E. Nedivi, Inhibitory Synapses Are Repeatedly Assembled and Removed at Persistent Sites In Vivo. Neuron, 2016. 89(4): p. 756-69.
  7. Carr, J.A., T.A. Valdez, O.T. Bruns, and M.G. Bawendi, Using the shortwave infrared to image middle ear pathologies. Proc Natl Acad Sci U S A, 2016. 113(36): p. 9989-94.
  8. Bruns OT, Bischof TS, Harris DK, Franke D, Shi Y, Riedemann L, Bartelt A, Jaworski FB, Carr JA, Rowlands CJ, Wilson MWB, Chen O, Wei H, Hwang GW, Montana D, Coropceanu I, Achorn OB, Kloepper J, Heeren J, Fukumura D, Jensen KF, Jain RK, Bawendi M, Next generation in vivo optical imaging with short-wave infrared quantum dots, Nature Biomedical Engineering
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