Imaging-guided bioresorbable acoustic hydrogel microrobots

Creators: Han, Hong¹; Ma, Xiaotian¹; Deng, Weiting¹; Zhang, Junhang²; Tang, Songsong¹; Pak, On Shun³; Zhu, Lailai⁴; Criado-Hidalgo, Ernesto¹; Gong, Chen²; Karshalev, Emil¹; Yoo, Jounghyun¹; You, Ming¹; Liu, Ann¹; Wang, Canran¹; Shen, Hao K.¹; Patel, Payal N.¹; Hays, Claire L.¹; Gunnarson, Peter J.¹; Li, Lei¹; Zhang, Yang¹; Dabiri, John Oluseun¹; Wang, Lihong V.¹; Shapiro, Mikhail G.¹; Wu, Di¹; Zhou, Qifa²; Greer, Julia R.¹; Gao, Wei¹

1. California Institute of Technology
2. University of Southern California
3. Santa Clara University
4. National University of Singapore

Abstract

Micro- and nanorobots excel in navigating the intricate and often inaccessible areas of the human body, offering immense potential for applications such as disease diagnosis, precision drug delivery, detoxification, and minimally invasive surgery. Despite their promise, practical deployment faces hurdles, including achieving stable propulsion in complex in vivo biological environments, real-time imaging and localization through deep tissue, and precise remote control for targeted therapy and ensuring high therapeutic efficacy. To overcome these obstacles, we introduce a hydrogel-based, imaging-guided, bioresorbable acoustic microrobot (BAM) designed to navigate the human body with high stability. Constructed using two-photon polymerization, a BAM comprises magnetic nanoparticles and therapeutic agents integrated into its hydrogel matrix for precision control and drug delivery. The microrobot features an optimized surface chemistry with a hydrophobic inner layer to substantially enhance microbubble retention in biofluids with multiday functionality and a hydrophilic outer layer to minimize aggregation and promote timely degradation. The dual-opening bubble-trapping cavity design enables a BAM to maintain consistent and efficient acoustic propulsion across a range of biological fluids. Under focused ultrasound stimulation, the entrapped microbubbles oscillate and enhance the contrast for real-time ultrasound imaging, facilitating precise tracking and control of BAM movement through wireless magnetic navigation. Moreover, the hydrolysis-driven biodegradability of BAMs ensures its safe dissolution after treatment, posing no risk of long-term residual harm. Thorough in vitro and in vivo experimental evidence demonstrates the promising capabilities of BAMs in biomedical applications. This approach shows promise for advancing minimally invasive medical interventions and targeted therapeutic delivery.

Copyright and License

Acknowledgement

We acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute at Caltech. We thank H. Li and Y. Yao for valuable inputs, D. M. Silevitch for support in characterizing the magnetic properties of BAMs, and A. Dolev for useful discussions on numerical simulations. We also acknowledge Port Therapeutics for providing access to the IVIS. Figures 2O, 3H, 4A, 4H, 4J, 4L, and 5A were created with BioRender.

Funding

This work was supported by National Science Foundation [grant 1931214 (to W.G.) and grants 1931292 and 2323046 (to O.S.P.)]; Heritage Medical Research Institute (to W.G.); Singapore Ministry of Education Academic Research Fund [MOE-T2EP50221-0012 (to L.Z.)]; National Institutes of Health grants R01EY030126, R01EY032229, and R01EY035084 (to Q.Z.); Army Research Office through Institute for Collaborative Biotechnologies (to J.R.G.); Caltech DeepMIC Center, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation (to D.W. and M.G.S.); and David and Lucile Packard Foundation (to M.G.S.).

Contributions

Conceptualization: W.G. and H.H. Methodology: H.H., X.M., W.D., J.Z., and S.T. Investigation: H.H., X.M., W.D., J.Z., S.T., O.S.P., L.Z., E.C.-H., C.G., E.K., J.Y., M.Y., A.L., C.W, H.K.S., P.N.P., C.L.H., P.J.G., L.L., Y.Z., J.O.D., L.V.W., M.G.S., and D.W. Visualization: H.H., X.M., J.Z., D.W., L.L., and Y.Z. Funding acquisition: W.G., O.S.P., M.G.S., Q.Z., and J.R.G. Project administration: W.G. Supervision: W.G., D.W., Q.Z., and J.R.G. Writing—original draft: W.G., H.H., and X.M. Writing—review and editing: H.H., X.M., W.D., J.Z., S.T., O.S.P., L.Z., E.C.-H., C.G., E.K., J.Y., M.Y., A.L., C.W, H.K.S., P.N.P., C.L.H., P.J.G., L.L., Y.Z., J.O.D., L.V.W., M.G.S., D.W., Q.Z., J.R.G., and W.G.

Data Availability

All data needed to support the conclusions of this manuscript are included in the main text or Supplementary Materials.

Supplemental Material

Supplementary mateirals are available: https://www.science.org/doi/full/10.1126/scirobotics.adp3593#supplementary-materials

The PDF file includes:
Methods
Figs. S1 to S21
Tables S1 and S2
Legends for movies S1 to S10
References (59–65)

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