Cellular Cargo Delivery: Toward Assisted Fertilization by Sperm-Carrying Micromotors

Abstract

We present artificially motorized sperm cells-a novel type of hybrid micromotor, where customized microhelices serve as motors for transporting sperm cells with motion deficiencies to help them carry out their natural function. Our results indicate that metal-coated polymer microhelices are suitable for this task due to potent, controllable, and nonharmful 3D motion behavior. We manage to capture, transport, and release single immotile live sperm cells in fluidic channels that allow mimicking physiological conditions. Important steps toward fertilization are addressed by employing proper means of sperm selection and oocyte culturing. Despite the fact that there still remain some challenges on the way to achieve successful fertilization with artificially motorized sperms, we believe that the potential of this novel approach toward assisted reproduction can be already put into perspective with the present work.

Guidance and Self‐Sorting of Active Swimmers: 3D Periodic Arrays Increase Persistence Length of Human Sperm Selecting for the Fittest

“…Moreover, the similarities in fluid physics of swimmers across different species,46 from bacteria to parasites, make these findings broadly applicable to other motile microorganisms. In fact, many such active swimmers across diverse biological systems have been an inspiration for the design of artificial micrometer‐scale flagellar systems including biohybrid microrobots,47, 48, 49, 50, 51, 52 and we also envision broad applications of our findings in areas such as medical diagnosis,53 biosensing,54 and targeted drug delivery 55…”

Medical microbots need better imaging and control

“…And we have used rotating magnets to drive a helixshaped physical micromotor to deliver a live but immotile bovine sperm cell to an oocyte (egg). Such 'spermbots' could lead to new assisted-reproduction techniques 8,9 . Low sperm count and motility are the two main causes of male infertility, accounting for 40% of all cases.…”

Micro- and nano-motors: the New Generation of Drug Carriers

“…In the same year, Schmidt's group reported the controlled manipulation and release of multiple micro objects [39], including cells, [21] using rolled-up catalytic microengines. This work opened a way to transport cells on demand to build or repair tissues, as now has been shown by several groups [25,[40][41]. The release of such cargo was also achieved by a fast change of the micromotor direction.…”

“…Apart from several substances on the membrane which can protect loaded drugs from clearance by immunosuppression, [88] their unique acrosome structure was confirmed to be able to induce cell fusion between sperms and somatic cells [89]. Magdanz et al [26] and Medina-Sanchez et al [25] reported the use of micromotors to guide or transport motile and immotile sperms to eventually overcome two of the main male infertility problems: oligozoospermia (low sperm count) and asthenozoospermia (poor sperm motility), respectively. In our group, a sperm-hybrid micromotor system was also developed as a new drug-delivery system to potentially treat diseases in the female reproductive tract ( Figure 3D & Table 2) [24,82].…”

“…Moreover, they can be controlled precisely using external sources such as magnetic fields, ultrasound or light [20]. For example, they have been used to isolate cells [21], perform microbiopsies [22], sense proteins [23], ligands or other molecules of interest, deliver drugs or even help sperms with motion deficiencies to reach the oocyte, all in vitro [24][25][26][27]. Nonetheless, it is worth noting that the use of these new systems entails additional difficulties, such as their control and visualization in deep tissue in real time [28].…”