Medical microbots to support new assisted reproduction techniques

Project Information

MicroRepro

Grant agreement ID: 835268

DOI

10.3030/835268

Project closed

EC signature date 25 June 2019

Start date 1 November 2019

End date 30 April 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 496 141,00

EU contribution

€ 2 496 141,00

Coordinated by

TECHNISCHE UNIVERSITAET CHEMNITZ
Germany

Periodic Reporting for period 4 - MicroRepro (Medical microbots to support new assisted reproduction techniques)

Reporting period: 2023-04-01 to 2024-09-30

Summary of the context and overall objectives of the project

Infertility is a health issue with sociological and psychological implications that affects approximately 50 million couples
worldwide and therefore receives global attention. Among fertility issues, male infertility is diagnosed in about 40% of all
cases and the major causes are poor motility of spermatozoa (asthenospermia), low sperm count (oligospermia), abnormal
sperm morphology (teratospermia) and/or combinations of these, leading to their inability to fertilize an oocyte. Such
problems have been mainly addressed by artificial insemination (AI) and in vitro fertilization (IVF). AI involves introducing
sperms into a woman’s uterus with a medical instrument, but its applicability is limited and its success rate is below 30%. In
contrast, IVF and intracytoplasmic sperm injection can be more effective but implicate more invasive procedures such as
removing oocytes from a woman’s ovaries, fertilize them outside of the body and then transfer the embryos back to the
uterus a few days later. These difficulties demand rethinking of assisted fertilization and the sought after novel approaches
that offer more natural procedures with high success rate. Hence, the objective of this project is to use untethered medical microbots to assist sperm
cells to fertilize an oocyte in living organisms (mice model). The MicroRepro project will bring advances in areas such as
bioimaging, nanomaterials science and fundamental biology, boosting the whole field of medical microbots in the process.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We have demosntrated real-time tracking of single microrobots below centimeter thick phantom tissue and ex vivo chicken breast using multispectral optoacoustic tomography. This technique combines the advantages of ultrasound imaging regarding depth and resolution with the molecular specificity of optical methods, thereby facilitating the discrimination between the spectral signatures of the microrobots from those of intrinsic tissue molecules.
We also employed high frequency ultrasound and photoacoustic imaging to obtain anatomical and molecular information, respectively, of magnetically driven micromotors in vitro and under ex vivo tissues. Furthermore, the steerability of the micromotors was demonstrated by the action of an external magnetic field into the uterus and bladder of living mice in real-time, being able to discriminate the micromotor signal from one of the endogenous chromophores by multispectral analysis. Finally, the successful loading and release of a model cargo by the micromotors toward non-invasive in vivo medical interventions was demonstrated.

An integrated system combining a magnetically‐driven micromotor and a synthetized protein‐based hyaluronic acid microflake was used for the in situ selection and transport of multiple motile sperm cells. This biodegradable system appeals for targeted sperm delivery in the reproductive system to assist fertilization or to deliver drugs.

We developed a powerful hybrid sperm micromotor that can actively swim against flowing natural fluids (continuous and pulsatile) and perform cargo delivery. In this biohybrid system, the sperm flagellum provides a high propulsion force while the synthetic microstructure serves for magnetic guidance and cargo transport. Single sperm micromotors can assemble into a train-like carrier after magnetization, allowing the transport of multiple sperm or medical cargoes to the area of interest.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The development of hybrid sperm carrying microrobots that are biodegradable and can efficiently swim and deliver cargo against the flow of natural fluids goes beyond state of the art. Optoacoustic imaging of microrobots in deep tissue in real time in 3D both in phantom tissue and in living mice has been reported for the first time and lay down the foundation for future in-vivo experiments where the first microrobotic-assisted fertilization is expected to be demonstrated.

Immobilization, transport and delivery of a swarm of motile sperm.