robotics.sciencemag.org/cgi/c
ontent/full/4/32/eaax0613/DC1
Supplementary Materials for
A microrobotic system guided by
photoacoustic c
omputed tomograp
hy for targeted
navigation in intestines in vivo
Zhiguang Wu, Lei Li, Yiran Yang, Peng Hu, Yang Li, So-Yoon Yang
, Lihong V. Wang*, Wei Gao*
*Corresponding author. Email: lvw@caltech.edu (L.V.W.); weigao@
caltech.edu (W.G.)
Published 24 July 2019,
Sci. Robot.
4
, eaax0613 (2019)
DOI: 10.1126/scirobotics.aax0613
The PDF file includes:
Text S1. Small-animal whole-body
imaging modalities and PACT
Fig. S1. The fabrication flow of t
he ingestible micromotors.
Fig. S2. The preparation of the MCs.
Fig. S3. Bright-field and fluores
cence microscopic images of th
e micromotors confirming the
successful drug loading in micromotors.
Fig. S4. Bright-field and fluores
cence microscopic images of th
e MCs confirming the successful
drug loading in the MCs.
Fig. S5. Dependence of the size
of the MCs on the rotation spee
d of magnetic stirring.
Fig. S6. Long-term stability of the
PA signals of the MCs under
the NIR illumination used in the
PACT in vitro and in vivo.
Fig. S7. Fluorescence imaging of t
he MCs in a silicone tube und
er tissues with different depths.
Fig. S8. Long-term structure stabi
lity of the MCs in the gastri
c fluid and the intestinal fluid.
Fig. S9. Velocities of Mg-based m
icromotors in the different me
dia.
Fig. S10. Velocities of bare Mg m
icroparticles in the different
media.
Fig. S11. Quantification of
MC migration speeds.
Fig. S12. Characterization of Mg di
ssolution in micromotors 12
hours after administration.
Fig. S13. Effects of cross-linking and DOX loading amount on th
e EE of the micromotors and
dose per micromotor.
Fig. S14. Profile of DOX release fr
om MCs and micromotors as a
function of time.
Fig. S15. The weight changes of the
mice after the oral adminis
tration of the MCs and the
control (DI water).
References (
50
–
55
)
Other Supplementary Material for
this manuscript includes the f
ollowing:
(available at robotics.sciencem
ag.org/cgi/content/full/4/32/eaa
x0613/DC1)
Movie S1 (.avi format). Animated illustration of the PAMR in vivo.
Movie S2 (.avi format). PA imaging
of
th
e migration of a MC in mo
del intestines.
Movie S3 (.avi format).
NIR-triggered destruction of
the MC and activated
autonomous
propulsion of the ingestible
m icromotors.
Movie S4 (.avi format).
Propulsi
on of the micromotors in bioflu
ids.
Movie S5 (.avi format). PA
imag ing of the MCs in vivo for 7.5 h
ours.
Mo
vie S6 (.avi format). PA imaging of the migration of an MC to
ward a
model colon tumor in
intestines.
Text
S1
. Small
-
animal whole
-
body imaging modalities and photoacoustic computed
tomography
Previously, small
-
animal whole
-
body imaging has typically relied on non
-
optical approaches,
including X
-
ray computed tomography (X
-
ray CT), magnetic resonance
imaging (MRI), positron
emission tomography (PET) or single
-
photon emission computed tomography (SPECT), and
ultrasound imaging (USI) (
1
6
). Although these techniques provide deep penetration, they suffer
from significant limitations. For example, microscop
ic MRI requires a long data acquisition time,
ranging from seconds to minutes, too slow for imaging dynamics
(
50
,
51
). More importantly, MRI,
requiring a strong magnetic field, is incompatible with magnetically driven or guided micromotors
(
5
). X
-
ray CT ha
s poor contrast of the micromotors made of biocompatible/biodegradable metals
(
15
,
52
). PET/SPECT alone suffers from poor spatial resolution. In addition, X
-
ray CT and
PET/SPECT employ ionizing radiation, which inhibits longitudinal monitoring (
53
). USI do
es not
image extravascular molecular contrasts (
54
). In addition, the MCs described in this manuscript
are mainly by mass composed of gelatin, which has almost the same acoustic impedance as soft
tissue (
55
). Thus, USI cannot image the MCs with sufficient
contrast
in vivo
. Optical imaging uses
non
-
carcinogenic electromagnetic waves to provide extraordinary molecular contrasts with either
endogenous or exogenous agents at high spatiotemporal resolution. Unfortunately, the strong
optical scattering of tissue
hampers the application of conventional optical imaging technologies
to small
-
animal whole body imaging at high spatial resolution (
1
6
). To date, photoacoustic
tomography (PAT) is the only optical imaging modality that breaks the optical diffusion limit (
1
7
)
on penetration and achieves high
-
resolution imaging in deep tissues with optical contrasts.
As a major incarnation of PAT, photoacoustic computed tomography (PACT) has attained high
spatiotemporal resolution, deep penetration, and anatomical and molecul
ar contrasts. Typically,
when implemented in PACT, a laser pulse broadly illuminates the whole tissue to be imaged. As
photons propagate inside the tissue, some are absorbed by molecules, and their energy is partially
or completely converted into heat, cre
ating a temperature rise through nonradiative relaxation. The
local temperature rise induces a pressure rise through thermoelastic expansion. The pressure rise
propagates, at a speed of roughly 1500 m s
-
1
, inside the tissue as a photoacoustic wave, and is
detected outside the tissue by an ultrasonic transducer or transducer array. The detected
photoacoustic signals are processed by a computer to form an image, which maps the original
optical energy deposition in the biological tissue. Because ultrasound sca
ttering in soft tissue is
about three orders of magnitude weaker than light scattering on a per unit path length basis in the
ultrasonic frequency of interest, PACT has achieved superb spatial resolution at depths by
detecting ultrasound.
Fig. S1.
The
fabrication flow of the ingestible micromotors
.
Fig. S2.
The preparation of the MCs.
Fig. S3.
Bright field and fluorescence microscopic images of the micromotors confirming the
successful drug loading in micromotors. Scale bar, 20
μ
m
.
Fig. S4.
Bright field and fluorescence
microscopic
images of the MCs confirming the successful
drug loading in the MCs. Scale bar, 20
μ
m.