Non-invasive optical focusing inside scattering media is still a big challenge because inhomogeneous media scatter 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 inside scattering media using only a linear fluorescent signal. The 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 μm diameter) and high intensity (more than a 100-fold enhancement) inside the scattering media. Our method promises a route in life science toward focusing, imaging, or manipulating deep into biological tissues with linear fluorescent agents.

1.
I. M.
Vellekoop
and
A. P.
Mosk
, “
Focusing coherent light through opaque strongly scattering media
,”
Opt. Lett.
32
,
2309
(
2007
).
2.
A. P.
Mosk
,
A.
Lagendijk
,
G.
Lerosey
, and
M.
Fink
, “
Controlling waves in space and time for imaging and focusing in complex media
,”
Nat. Photonics
6
,
283
(
2012
).
3.
X.
Tao
,
T.
Lam
,
B.
Zhu
,
Q.
Li
,
M. R.
Reinig
, and
J.
Kubby
, “
Three-dimensional focusing through scattering media using conjugate adaptive optics with remote focusing (CAORF)
,”
Opt. Express
25
,
10368
(
2017
).
4.
V.
Tran
,
S. K.
Sahoo
,
D.
Tang
, and
C.
Dang
, “
Utilizing optical conjugate plane to enhance 3D focusing and forming shapes behind turbid media
,”
Proc. SPIE
10886
,
108861C
(
2019
).
5.
I. M.
Vellekoop
,
E. V.
Putten
,
A.
Lagendijk
, and
A. P.
Mosk
, “
Demixing light paths inside disordered metamaterials
,”
Opt. Express
16
,
67
(
2008
).
6.
R.
Horstmeyer
,
H.
Ruan
, and
C.
Yang
, “
Guidestar-assisted wavefront-shaping methods for focusing light into biological tissue
,”
Nat. Photonics
9
,
563
(
2015
).
7.
X.
Xu
,
H.
Liu
, and
L. V.
Wang
, “
Time-reversed ultrasonically encoded optical focusing into scattering media
,”
Nat. Photonics
5
,
154
(
2011
).
8.
B.
Judkewitz
,
Y. M.
Wang
,
R.
Horstmeyer
,
A.
Mathy
, and
C.
Yang
, “
Speckle-scale focusing in the diffusive regime with time-reversal of variance-encoded light (TROVE)
,”
Nat. Photonics
7
,
300
(
2013
).
9.
T.
Chaigne
,
O.
Katz
,
A. C.
Boccara
,
M.
Fink
,
E.
Bossy
, and
S.
Gigan
, “
Controlling light in scattering media noninvasively using the photo-acoustic transmission-matrix
,”
Nat. Photonics
8
,
58
(
2014
).
10.
C.
Ma
,
X.
Xu
,
Y.
Liu
, and
L. V.
Wang
, “
Time-reversed adapted-perturbation (TRAP) optical focusing onto dynamic objects inside scattering media
,”
Nat. Photonics
8
,
931
(
2014
).
11.
J.
Tang
,
R. N.
Germain
, and
M.
Cui
, “
Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique
,”
Proc. Natl. Acad. Sci. U. S. A.
109
,
8434
(
2012
).
12.
O.
Katz
,
E.
Small
,
Y.
Guan
, and
Y.
Silberberg
, “
Noninvasive nonlinear focusing and imaging through strongly scattering turbid layers
,”
Optica
1
,
170
(
2014
).
13.
R.
Fiolka
,
K.
Si
, and
M.
Cui
, “
Complex wavefront corrections for deep tissue focusing using low coherence backscattered light
,”
Opt. Express
20
,
16532
(
2012
).
14.
S. M.
Popoff
,
G.
Lerosey
,
R.
Carminati
,
M.
Fink
,
A. C.
Boccara
, and
S.
Gigan
, “
Measuring the transmission matrix in optics: An approach to the study and control of light propagation in disordered media
,”
Phys. Rev. Lett.
104
,
100601
(
2010
).
15.
S.
Jeong
,
Y. R.
Lee
,
W.
Choi
,
S.
Kang
,
J. H.
Hong
,
J. S.
Park
,
Y. S.
Lim
,
H. G.
Park
, and
W.
Choi
, “
Focusing of light energy inside a scattering medium by controlling the time-gated multiple light scattering
,”
Nat. Photonics
12
,
277
(
2018
).
16.
A.
Badon
,
D.
Li
,
G.
Lerosey
,
A. C.
Boccara
,
M.
Fink
, and
A.
Aubry
, “
Smart optical coherence tomography for ultra-deep imaging through highly scattering media
,”
Sci. Adv.
2
,
e1600370
(
2016
).
17.
S.
Kang
,
S.
Jeong
,
W.
Choi
,
H.
Ko
,
T. D.
Yang
,
J. H.
Joo
,
J. S.
Lee
,
Y. S.
Lim
,
Q. H.
Park
, and
W.
Choi
, “
Imaging deep within a scattering medium using collective accumulation of single-scattered waves
,”
Nat. Photonics
9
,
253
(
2015
).
18.
C.
Prada
and
M.
Fink
, “
Eigenmodes of the time reversal operator: A solution to selective focusing in multiple-target media
,”
Wave Motion
20
,
151
(
1994
).
19.
S. M.
Popoff
,
A.
Aubry
,
G.
Lerosey
,
M.
Fink
,
A. C.
Boccara
, and
S.
Gigan
, “
Exploiting the time-reversal operator for adaptive optics, selective focusing, and scattering pattern analysis
,”
Phys. Rev. Lett.
107
,
263901
(
2011
).
20.
G.
Stern
and
O.
Katz
, “
Noninvasive focusing through scattering layers using speckle correlations
,”
Opt. Lett.
44
,
143
(
2019
).
21.
A.
Boniface
,
B.
Blochet
,
J.
Dong
, and
S.
Gigan
, “
Noninvasive light focusing in scattering media using speckle variance optimization
,”
Optica
6
,
1381
(
2019
).
22.
I. M.
Vellekoop
, “
Feedback-based wavefront shaping
,”
Opt. Express
23
,
12189
(
2015
).
23.
S. K.
Sahoo
,
D.
Tang
, and
C.
Dang
, “
Single-shot multispectral imaging with a monochromatic camera
,”
Optica
4
,
1209
(
2017
).
24.
A. K.
Singh
,
D. N.
Naik
,
G.
Pedrini
,
M.
Takeda
, and
W.
Osten
, “
Exploiting scattering media for exploring 3D objects
,”
Light: Sci. Appl.
6
,
e16219
(
2017
).
25.
J. W.
Goodman
,
Speckle Phenomena in Optics: Theory and Applications
(
Roberts & Company Publishers
,
2006
), pp.
23
40
.
26.
B.
Thierry
,
X.
Antoine
,
C.
Chniti
, and
H.
Alzubaidi
, “
Mu-diff: An open-source matlab toolbox for computing multiple scattering problems by disks
,”
Comput. Phys. Commun.
192
,
348
(
2015
).
27.
E.
Edrei
and
G.
Scarcelli
, “
Focusing through scattering medium: A fundamental trade-off between speckle size and intensity enhancement
,” arXiv:1808.07830 (
2018
).
28.
H. P.
Paudel
,
C.
Stockbridge
,
J.
Mertz
, and
T.
Bifano
, “
Focusing polychromatic light through strongly scattering media
,”
Opt. Express
21
,
17299
(
2013
).
29.
C.
Park
,
J.-H.
Park
,
C.
Rodriguez
,
H.
Yu
,
M.
Kim
,
K.
Jin
,
S.
Han
,
J.
Shin
,
S. H.
Ko
,
K. T.
Nam
,
Y.-H.
Lee
,
Y.-H.
Cho
, and
Y.
Park
, “
Full-field subwavelength imaging using a scattering superlens
,”
Phys. Rev. Lett.
113
,
113901
(
2014
).
30.
E.
Edrei
and
G.
Scarcelli
, “
Memory-effect based deconvolution microscopy for super-resolution imaging through scattering media
,”
Sci. Rep.
6
,
33558
(
2016
).
31.
H.
Zhuang
,
H.
He
,
X.
Xie
, and
J.
Zhou
, “
High speed color imaging through scattering media with a large field of view
,”
Sci. Rep.
6
,
032696
(
2016
).
32.
D.
Tang
,
S. K.
Sahoo
,
V.
Tran
, and
C.
Dang
, “
Single-shot large field of view imaging with scattering media by spatial demultiplexing
,”
Appl. Opt.
57
,
7533
(
2018
).
33.
S.
Ludwig
,
B. L.
Teurnier
,
G.
Pedrini
,
X.
Peng
, and
W.
Osten
, “
Image reconstruction and enhancement by deconvolution in scatter-plate microscopy
,”
Opt. Express
27
,
23049
(
2019
).
34.
X.
Zhu
,
S. K.
Sahoo
,
D.
Wang
,
H. Q.
Lam
,
P. A.
Surman
,
D.
Li
, and
C.
Dang
, “
Single-shot multi-view imaging enabled by scattering lens
,”
Opt. Express
27
,
37164
(
2019
).

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