Non-invasive optical focusing inside strongly scattering media with linear fluorescence

Non-invasive optical focusing inside scattering media is still a big challenge because inhomogeneous media scatter both incoming photons for focusing and outgoing photons for observation. Various approaches, utilizing non-linear fluorescence or ultrasound, have been reported to address this difficulty. However, implementation of these methods is complicated and highly expensive, as ultrafast laser systems or photo-acoustic equipment must be employed. Here, we demonstrate a wavefront shaping technique to achieve non-invasive focusing (NiF) inside scattering media using only a linear fluorescent signal. Contrast and mean of incoherent speckles, produced by the linear fluorescence, are utilized as feedback signals to optimize the input wavefront. While increasing speckle contrast makes the focus tighter, and increasing the speckle mean enhances the intensity, fine-tuning the contribution of these two factors in our two-step optimization is essential. An optimal wavefront is found to achieve simultaneously both a micrometer focal spot size (down to 20 um diameter) and high intensity (more than a 100-fold enhancement) inside the scattering media. Our method promises a new route in life science towards focusing, imaging or manipulating deep into biological tissues with linear fluorescent agents.

[1]  Mathias Fink,et al.  Eigenmodes of the time reversal operator: a solution to selective focusing in multiple-target media , 1994 .

[2]  A. Mosk,et al.  Focusing coherent light through opaque strongly scattering media. , 2007, Optics letters.

[3]  E. G. van Putten,et al.  Demixing light paths inside disordered metamaterials. , 2008, Optics express.

[4]  S. Popoff,et al.  Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media. , 2009, Physical review letters.

[5]  Jason D. Schmidt,et al.  Numerical Simulation of Optical Wave Propagation With Examples in MATLAB , 2010 .

[6]  Lihong V. Wang,et al.  Time-reversed ultrasonically encoded optical focusing into scattering media , 2010, Nature photonics.

[7]  Jianyong Tang,et al.  Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique , 2012, Proceedings of the National Academy of Sciences.

[8]  M. Fink,et al.  Exploiting the time-reversal operator for adaptive optics, selective focusing and scattering pattern analysis , 2011, 2012 Conference on Lasers and Electro-Optics (CLEO).

[9]  Ke Si,et al.  Complex wavefront corrections for deep tissue focusing using low coherence backscattered light , 2012 .

[10]  G. Lerosey,et al.  Controlling waves in space and time for imaging and focusing in complex media , 2012, Nature Photonics.

[11]  Jerome Mertz,et al.  Focusing polychromatic light through strongly scattering media. , 2013, Optics express.

[12]  Ying Min Wang,et al.  Speckle-scale focusing in the diffusive regime with time-reversal of variance-encoded light (TROVE) , 2013, Nature Photonics.

[13]  Yongkeun Park,et al.  Full-field subwavelength imaging using a scattering superlens. , 2014, Physical review letters.

[14]  O. Katz,et al.  Noninvasive nonlinear focusing and imaging through strongly scattering turbid layers , 2014, 1405.4826.

[15]  Yan Liu,et al.  Time-reversed adapted-perturbation (TRAP) optical focusing onto dynamic objects inside scattering media , 2014, Nature Photonics.

[16]  M. Fink,et al.  Controlling light in scattering media non-invasively using the photoacoustic transmission matrix , 2013, 1305.6246.

[17]  I. Vellekoop.  Feedback-based wavefront shaping. , 2015, Optics express.

[18]  Xavier Antoine,et al.  μ-diff: An open-source Matlab toolbox for computing multiple scattering problems by disks , 2014, Comput. Phys. Commun..

[19]  Sungsam Kang,et al.  Imaging deep within a scattering medium using collective accumulation of single-scattered waves , 2015, Nature Photonics.

[20]  Jerome Mertz,et al.  Field of view advantage of conjugate adaptive optics in microscopy applications. , 2015, Applied optics.

[21]  Changhuei Yang,et al.  Guidestar-assisted wavefront-shaping methods for focusing light into biological tissue , 2015, Nature Photonics.

[22]  Jianying Zhou,et al.  High speed color imaging through scattering media with a large field of view , 2016, Scientific Reports.

[23]  Mathias Fink,et al.  Smart optical coherence tomography for ultra-deep imaging through highly scattering media , 2015, Science Advances.

[24]  Giuliano Scarcelli,et al.  Memory-effect based deconvolution microscopy for super-resolution imaging through scattering media , 2016, Scientific Reports.

[25]  Wolfgang Osten,et al.  Exploiting scattering media for exploring 3D objects , 2016, Light: Science & Applications.

[26]  J. Kubby,et al.  Three-dimensional focusing through scattering media using conjugate adaptive optics with remote focusing (CAORF). , 2017, Optics express.

[27]  Sungsam Kang,et al.  Focusing of light energy inside a scattering medium by controlling the time-gated multiple light scattering , 2017 .

[28]  S. Sahoo,et al.  Single-shot multispectral imaging with a monochromatic camera , 2017, 1707.09453.

[29]  Sujit Kumar Sahoo,et al.  Single-shot large field of view imaging with scattering media by spatial demultiplexing. , 2017, Applied optics.

[30]  Dong Wang,et al.  Single-shot multi-view imaging enabled by scattering lens. , 2019, Optics express.

[31]  G. Pedrini,et al.  Image reconstruction and enhancement by deconvolution in scatter-plate microscopy. , 2019, Optics express.

[32]  Cuong Dang,et al.  Utilizing optical conjugate plane to enhance 3D focusing and forming shapes behind turbid media , 2019, BiOS.

[33]  Ori Katz,et al.  Noninvasive focusing through scattering layers using speckle correlations. , 2018, Optics letters.

[34]  Jonathan Dong,et al.  Noninvasive light focusing in scattering media using speckle variance optimization , 2019, Optica.

[35]  G. Scarcelli,et al.  Focusing through scattering medium: a fundamental trade-off between speckle size and intensity enhancement (Conference Presentation) , 2018, Adaptive Optics and Wavefront Control for Biological Systems V.