Stratified Disk Microrobots with Dynamic Maneuverability and Proton-Activatable Luminescence for in Vivo Imaging

Abstract

Microrobots can expand our abilities to access remote, confined, and enclosed spaces. Their potential applications inside our body are obvious, e.g., to diagnose diseases, deliver medicine, and monitor treatment efficacy. However, critical requirements exist in relation to their operations in gastrointestinal environments, including resistance to strong gastric acid, responsivity to a narrow proton variation window, and locomotion in confined cavities with hierarchical terrains. Here, we report a proton-activatable microrobot to enable real-time, repeated, and site-selective pH sensing and monitoring in physiological relevant environments. This is achieved by stratifying a hydrogel disk to combine a range of functional nanomaterials, including proton-responsive molecular switches, upconversion nanoparticles, and near-infrared (NIR) emitters. By leveraging the 3D magnetic gradient fields and the anisotropic composition, the microrobot can be steered to locomote as a gyrating “Euler’s disk”, i.e., aslant relative to the surface and along its low-friction outer circumference, exhibiting a high motility of up to 60 body lengths/s. The enhanced magnetomotility can boost the pH-sensing kinetics by 2-fold. The fluorescence of the molecular switch can respond to pH variations with over 600-fold enhancement when the pH decreases from 8 to 1, and the integration of upconversion nanoparticles further allows both the efficient sensitization of NIR light through deep tissue and energy transfer to activate the pH probes. Moreover, the embedded down-shifting NIR emitters provide sufficient contrast for imaging of a single microrobot inside a live mouse. This work suggests great potential in developing multifunctional microrobots to perform generic site-selective tasks in vivo.

Spatiotemporally Mapping Thermodynamics of Lysosomes and Mitochondria using Cascade Organelle-Targeting Upconversion Nanoparticles

“…Therefore, it is desirable to simultaneously monitor the pH dynamics in lysosomes during the temperature measurement. As UCNPs have been used to sense the in situ pH values [37], it would be feasible to develop the “all-in-one” nanoscale sensors based on LysoDots.…”

Responsive Magnetic Nanocomposites for Intelligent Shape-Morphing Microrobots

“…The light-induced heating for morphing the shape might not work inside the human body. In this respect, NIR-absorbing particles should be assessed as active particles for thermal coupling …”

“…Microrobots are the next generation of microscale systems processing intriguing functionalities, with sizes typically in the range of a few microns to submillimeters. Such systems are comparable in size with biological cells, tissues, and human cavitary structures (e.g., gastrointestinal and blood circulatory systems), which makes them suitable for performing tasks that require the delicate manipulation of small biological entities and at locations that are often hard to reach by human beings. − Microrobots may also interact with molecules and cellular and tissue samples, in which the effective transduction of mechanical forces/torques is critical for not only controlling biophysical processes but also for clinical theragnostic applications. − …”

Responsive Sensors of Upconversion Nanoparticles

“…Upconverting nanomaterials can play a role in the technological trend toward system-level integration of an intelligent dust-scale robotic system, through approaches such as monolithic growth of the nanocrystals with magnetic structure or embedding them in strained and biocompatible hydrogel matrixes, while contributing minimally to the overall device footprint. Recently, a stratified disk robot with monolithically integrated magneto-mobility, proton sensing, and NIR-II imaging ability was reported, which showcased the potential of “upconverting sensing robots” for conducting multiple tasks for in vivo applications . Robots could be powered directly by NIR light for full optical actuation and tracking (Figure H) .…”

“…Recently, a stratified disk robot with monolithically integrated magneto-mobility, proton sensing, and NIR-II imaging ability was reported, which showcased the potential of "upconverting sensing robots" for conducting multiple tasks for in vivo applications. 80 Robots could be powered directly by NIR light for full optical actuation and tracking (Figure 5H). 56 Crossing the biological barriers, such as gastrointestinal and hematological systems, could be achieved by magnetic steering and optical navigation of the sensing device to sites of interest.…”