Micro‐Bio‐Chemo‐Mechanical‐Systems: Micromotors, Microfluidics, and Nanozymes for Biomedical Applications

Abstract

Wireless nano‐/micromotors powered by chemical reactions and/or external fields generate motive forces, perform tasks, and significantly extend short‐range dynamic responses of passive biomedical microcarriers. However, before micromotors can be translated into clinical use, several major problems, including the biocompatibility of materials, the toxicity of chemical fuels, and deep tissue imaging methods, must be solved. Nanomaterials with enzyme‐like characteristics (e.g., catalase, oxidase, peroxidase, superoxide dismutase), that is, nanozymes, can significantly expand the scope of micromotors’ chemical fuels. A convergence of nanozymes, micromotors, and microfluidics can lead to a paradigm shift in the fabrication of multifunctional micromotors in reasonable quantities, encapsulation of desired subsystems, and engineering of FDA‐approved core–shell structures with tuneable biological, physical, chemical, and mechanical properties. Microfluidic methods are used to prepare stable bubbles/microbubbles and capsules integrating ultrasound, optoacoustic, fluorescent, and magnetic resonance imaging modalities. The aim here is to discuss an interdisciplinary approach of three independent emerging topics: micromotors, nanozymes, and microfluidics to creatively: 1) embrace new ideas, 2) think across boundaries, and 3) solve problems whose solutions are beyond the scope of a single discipline toward the development of micro‐bio‐chemo‐mechanical‐systems for diverse bioapplications.

Air-Filled Microbubbles Based on Albumin Functionalized with Gold Nanocages and Zinc Phthalocyanine for Multimodal Imaging

“…The sonication method was chosen for microbubbles preparation due to its simplicity and widespread use [ 53 ]. Air-filled microbubbles were obtained in saline solutions to track their properties in conditions close to physiological and to increase their compatibility.…”

Exhausted local lactate accumulation via injectable nanozyme-functionalized hydrogel microsphere for inflammation relief and tissue regeneration

“…Herein, nanozymes could be encapsulated in hydrogel pores and remain stable inside. The nanozyme-functionalized hydrogel microsphere prepared by microfluidic technology leads to the controllable catalytic reaction and sustained release of nanoparticles [ 39 ].…”

Microbubbles Stabilized by Protein Shell: From Pioneering Ultrasound Contrast Agents to Advanced Theranostic Systems

“…In flow-focusing devices, inner channels with a gaseous phase and outer channels with a continuous phase are merged into a small orifice, leading to MB formation. In T-junction devices, a continuous phase channel is placed perpendicular to a gas phase channel; thus, when gas penetrates the continuous phase under required pressure and flow velocity, local instability at the gas-liquid interface results in MB formation (Figure 3b) [10,[114][115][116][117]. However, the scalability of MB production with microfluidics remains the main current limitation.…”

“…Poor contrast image quality can limit US usability for pathology diagnosis applications, such as hypervascular malignancies, or breast, liver, and renal masses [7,8]. The administration of contrast agents, initially demonstrated by Gramiak and Shah in 1968, can provide echogenicity several orders of magnitude higher than solid particles of comparable size [9][10][11][12]. Over the years, gas-filled microbubbles (MBs) have become the most popular US contrast agents with the ability to behave as a non-linear oscillator and increase the detected signal intensity up to 1000 times.…”

“…Pioneering works of MB shell stabilization with albumin by Feinstein and Keller led to the regulatory approval of Albunex (Molecular Biosystems Inc., San Diego, CA, USA) MBs are colloidal systems with a mean diameter of 1-7 µm, acting as real blood pool agents. Beyond imaging applications, MBs are actively investigated as drug delivery systems due to their shell drug loading capacities and gaseous core US stimuliresponsiveness [10,[13][14][15][16]]. An MB shell is mainly stabilized with lipids, proteins, or polymers [17][18][19][20][21][22][23][24].…”