Biology subjects

Medina Sanchez, M.

Publications and source records attributed to Medina Sanchez, M..

5 recordsLinked to original sources

bioRxiv2026

Programmable microactuators phase-lock cilia to local oscillatory flow

Hydrodynamic synchronization of motile cilia is essential for biological functions such as fluid transport, locomotion, and developmental patterning. It comprises the generation and the response to local flows in complex geometries. Besides their central role in physiology, direct experimental tests of ciliary responses to local flows at cellular length and time scales have remained elusive, largely due to the absence of tools capable of applying controlled, and localized flow stimuli. Here, we introduce programmable, nanometer-thin Ti/Pt microactuators that generate well-defined hydrodynamic forcing at biologically relevant frequencies while operating at biocompatible sub-Volt voltages. This platform is pioneering a controlled local hydrodynamic stimulation of individual motile cilia. We quantify the flow fields and forces produced by single microactuators using particle image velocimetry. Applying local oscillatory flows close to motile cilia of the green alga Chlamydomonas reinhardtii, we probe their dynamic response by quantifying phase-locking between cilia and microactuators. This quantification is aided by combining machine-learning-based image segmentation, oscillator phase reconstruction, and circular statistics. During actuation, we observe signatures of phase-locking: those include a reversible modulation of the fluctuations in phase-difference between cilium and actuator and a systematic shift in ciliary beating frequency. Beyond providing a bio-compatible and precise platform for local hydrodynamic stimulation, our approach establishes an experimental framework for directly testing theories of hydrodynamic synchronization and load adaptation in systems of motile cilia.

biophysics↗

bioRxiv2025

Self-Propelling Adaptive Robotic Microcatheters Enabled by Scalable Fabrication for Intracorporeal Navigation

Minimally invasive therapies demand precise navigation through complex and delicate anatomical pathways, requiring medical tools that are small, flexible, and highly maneuverable. Here, we present a scalable fabrication platform for magnetic tubular microrobots, tethered and untethered, with programmable magnetization, enabling self-propulsion, and an adaptive remote control for targeted interventions. The platform uses Joule heating through a template wire for rapid, and reliable fabrication of microrobots with tunable dimensions. We demonstrate three device configurations: (1) a steerable guiding microcatheter with stiffness modulation; (2) an untethered tubular microrobot (TubeBot) exhibiting wave-crawling locomotion; and (3) a hybrid microcatheter robot that integrates distal-end wave-crawling propulsion with linear insertion to minimize tissue trauma. Validation in tortuous channels, soft phantoms replicating tissue compliance, 3D-printed organ models, ex vivo tissues, and live mice demonstrates the platforms ability to achieve precise microrobotic navigation. The successful targeted delivery of sperm cells, embryos, and drug-mimicking compounds further highlights its potential for precision medicine, including applications in assisted reproduction and targeted drug delivery.

bioengineering↗

bioRxiv2025

Magnetically Controlled Microrobots for In Vivo Non-Invasive Embryo Transfer

Infertility affects millions worldwide and is often linked to factors such as poor sperm quality and female reproductive organ disorders. Despite significant advancements in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), implantation rates remain low, ranging from 17 to 21% after three days of incubation, mainly due to stress, lifestyle factors, and uterine conditions. Extended embryo culture techniques have shown promise in improving pregnancy rates. However, the availability of high-quality blastocysts remains a major challenge. Intrafallopian transfer techniques, such as gamete/zygote intrafallopian transfer (GIFT/ZIFT), were introduced to improve fertilization and early embryo development, particularly for patients with repeated embryo implantation failure (10-30% of assisted reproduction technology (ART) cases, particularly in women >35). However, these methods have declined due to advancements in IVF and the variability in laparoscopy procedures used for GIFT/ZIFT. To address these challenges, we propose a non-invasive microrobotic embryo transfer ({micro}ET) technique using remotely controlled microcarriers comparable in size to embryos. We demonstrate the capabilities of magnetically actuated spiral microrobots, fabricated using laser direct writing for capturing, transporting, and releasing embryos into murine uteri. Additionally, we characterize their motion performance and implement image-guided closed-loop control and dual ultrasound (US)/photoacoustic (PA) tracking for deep-tissue interventions. Recognizing the importance of clinical translation, we present preliminary studies on gelatin-based microrobots, a biodegradable alternative, and explore endometrial remodeling after the in vivo transfer of microrobots carrying embryo-like structures. Our findings show that these microrobots can effectively transport embryos, support their development, and enable minimally invasive delivery, providing a more natural, targeted, and non-invasive strategy for in vivo assisted reproduction. One-Sentence SummaryWe propose a non-invasive {micro}ET technique using magnetically actuated microcarriers to improve embryo cargo-delivery in assisted reproduction, addressing challenges in infertility treatments by enabling precise, image-guided embryo delivery with minimal invasiveness.

bioengineering↗

bioRxiv2025

Photoacoustics-guided Real-Time Closed-loop Control of Magnetic Microrobots through Deep Learning

Medical microrobots promise to increase the efficacy and reduce the invasiveness of certain medical procedures in the future. Real-time tracking of the microrobot, actuation, and closed-loop control of its position under in vivo conditions is crucial to fulfill the task at hand. We present a system for closed-loop control of magnetic microrobots using dual-mode ultrasound and photoacoustic imaging. It employs GPU-accelerated beamforming and tracking to achieve real-time operation with a closed-loop cycle time of 100 ms. Artifacts from simultaneous imaging and magnetic actuation are suppressed through time-multiplexing. To address the challenge of detecting microrobots in low-contrast, strong-background images, we implemented real-time Deep Learning-based tracking. A custom dataset of various types of microrobots is curated from long-duration closed-loop control measurements and employed to fine-tune a pre-trained detection model. We introduce a platform for real-time closed-loop control of microrobots and demonstrate its performance with a 300 m spiral-shaped microrobot following a figure-of-8 shape under photoacoustic imaging guidance. The localization error is evaluated against an optical reference measurement. Our results show that photoacoustic-based tracking significantly outperforms ultrasound tracking, with the deep learning approach further reducing missed detections. This demonstrates the algorithms ability to generalize to a previously unseen type of microrobot. We envision this platform to advance medical microrobotics research by providing real-time closed-loop control of untethered microrobots under deep tissue.

bioengineering↗

bioRxiv2025

Influence of hyperparameters on the performance of deep learning-based microrobotic localization under phantom tissue

For the effective operation of medical microrobots within living organisms and precise targeting, it is imperative to employ imaging techniques closely integrated with real-time deep-tissue tracking methods. However, due to a typically low Signal-to-Noise ratio images with strong background, it is hard for traditional tracking methods to achieve sufficient accuracy. This challenge can be addressed by deep learning-based tracking with a real-time detection model. However, a multitude of design choices and Hyperparameters influence the performance. In this study we compared the influence of the hyperparameters and model architecture versions of the "you only look once" (YOLO) network. We use experimental data from a magnetic microrobot imaged with Photoacoustics through 5 mm phantom tissue to evaluate the tracking in comparison with an optical reference. The deep-learning based methods consistently achieved lower missing-detection ratios. Regarding the Root Mean Square localization error, we observed that increasing the weight of the box loss function and utilizing the distribution focal loss can enhance the performance by 10%. Furthermore, it can be seen that YOLOv9 consistently outperformed its predecessor YOLOv8. This study quantifies the robustness of deep-learning based tracking of medical microrobots under tissues.

bioengineering↗