Untethered mobile microrobots has the potential to leverage minimally invasive theranostic functions precisely and efficiently in hard-to-reach, confined, and delicate inner body sites. However, such a complex task requires an integrated design and engineering, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, magnetically powered and controlled, enzymatically degradable microswimmer, which is responsive to the pathological markers in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical architecture enabling volumetric cargo loading and swimming capabilities under rotational magnetic fields, and 3D printed such optimized 3D microswimmer (length: 20 µm and diameter: 6 µm) using two-photon polymerization from a magnetic precursor suspension comprised from gelatin methacryloyl and biofunctionalized superparamagnetic iron oxide nanoparticles. At normal physiological concentrations, we show that matrix metalloproteinase-2 (MMP-2) enzyme could entirely degrade the microswimmer in 118 h to solubilized non-toxic products. The microswimmer rapidly responds to the pathological concentrations of MMP-2 by swelling, and thereby boosting the release of the embedded cargo molecules. In addition to delivery of the drug type of therapeutic cargo molecules completely to the given microenvironment after full degradation, microswimmer can also release other functional cargos. As an example demonstration, Anti-ErbB 2 antibody-tagged magnetic nanoparticles are released from the fully degraded microswimmers for targeted labeling of SKBR3 breast cancer cells in vitro towards a potential future scenario of medical imaging of remaining cancer tissue sites after a microswimmer-based therapeutic delivery operation.

Bacteria-propelled biohybrid microswimmers have recently shown to be able to actively transport and deliver cargos encapsulated into their synthetic constructs to specific regions locally. However, usage of synthetic materials as cargo carriers can result in inferior performance in load-carrying efficiency, biocompatibility, and biodegradability, impeding clinical translation of biohybrid microswimmers. Here, we report construction and external guidance of bacteria-driven microswimmers using red blood cells (RBCs; erythrocytes) as autologous cargo carriers for active and guided drug delivery. Multifunctional biohybrid microswimmers were fabricated by attachment of RBCs [loaded with anticancer doxorubicin drug molecules and superparamagnetic iron oxide nanoparticles (SPIONs)] to bioengineered motile bacteria, Escherichia coli MG1655, via biotin-avidin-biotin binding complex. Autonomous and on-board propulsion of biohybrid microswimmers was provided by bacteria, and their external magnetic guidance was enabled by SPIONs loaded into the RBCs. Furthermore, bacteria-driven RBC microswimmers displayed preserved deformability and attachment stability even after squeezing in microchannels smaller than their sizes, as in the case of bare RBCs. In addition, an on-demand light-activated hyperthermia termination switch was engineered for RBC microswimmers to control bacteria population after operations. RBCs, as biological and autologous cargo carriers in the biohybrid microswimmers, offer notable advantages in stability, deformability, biocompatibility, and biodegradability over synthetic cargo-carrier materials. The biohybrid microswimmer design presented here transforms RBCs from passive cargo carriers into active and guidable cargo carriers toward targeted drug and other cargo delivery applications in medicine.

The development of new biosensor technologies and their active use as wearable devices have offered mobility and flexibility to conventional western medicine and personal fitness tracking. In the development of biosensors, transducers stand out as the main elements converting the signals sourced from a biological event into a detectable output. Combined with the suitable bio-receptors and the miniaturization of readout electronics, the functionality and design of the transducers play a key role in the construction of wearable devices for personal health control. Ever-growing research and industrial interest in new transducer technologies for point-of-care (POC) and wearable bio-detection have gained tremendous acceleration by the pandemic-induced digital health transformation. In this article, we provide a comprehensive review of transducers for biosensors and their wearable applications that empower users for the active tracking of biomarkers and personal health parameters.

A simple way to mitigate the potential negative side-effects associated with chemical lysis of a blood clot is to tear its fibrin network via mechanical rubbing using a helical robot. Here, we achieve mechanical rubbing of blood clots under ultrasound guidance and using external magnetic actuation. Position of the helical robot is determined using ultrasound feedback and used to control its motion toward the clot, whereas the volume of the clots is estimated simultaneously using visual feedback. We characterize the shear modulus and ultimate shear strength of the blood clots to predict their removal rate during rubbing. Our in vitro experiments show the ability to move the helical robot controllably toward clots using ultrasound feedback with average and maximum errors of ${\text{0.84}\pm \text{0.41}}$ and 2.15 mm, respectively, and achieve removal rate of $-\text{0.614} \pm \text{0.303}$ mm $^{3}$ /min at room temperature ( ${\text{25}}^{\circ }$ C) and $-\text{0.482} \pm \text{0.23}$ mm $^{3}$ /min at body temperature (37 $^{\circ}$ C), under the influence of two rotating dipole fields at frequency of 35 Hz. We also validate the effectiveness of mechanical rubbing by measuring the number of red blood cells and platelets past the clot. Our measurements show that rubbing achieves cell count of $(\text{46} \pm \text{10.9}) \times \text{10}^{4}$ cell/ml, whereas the count in the absence of rubbing is $(\text{2} \pm \text{1.41}) \times \text{10}^{4}$ cell/ml, after 40 min.

The risk of side effects from thrombolytic agents can be minimized by using smaller doses, assisted by mechanical rubbing against blood clots using helical robots. Quantifying this observation, we study the influence of rubbing against clots on their removal rate in vitro. First, we present a hydrodynamic model of the helical robot based on the resistive-force theory to investigate the rubbing behavior of the clots using robot driven by two rotating dipole fields. Second, we experimentally evaluate the influence of the rubbing on the removal rate of the blood clots. Not only do we find that the removal rate of mechanical rubbing (-0.56 ± 0.27 mm ³ /min) is approximately three times greater than the dissolution rate of chemical lysis using streptokinase (-0.17 ± 0.032 mm ³ /min), but we also show that this removal rate can be controlled via the rubbing speed of the robot.