In a groundbreaking advancement at the intersection of bioengineering and reproductive medicine, researchers at the University of Rome Tor Vergata have unveiled a pioneering robotic system leveraging optically-induced dielectrophoresis (ODEP) for the micromanipulation and detailed single-cell analysis of patient-derived endometrial stromal cells. This innovative platform holds transformative potential for the stratification of patients facing reproductive failure, illuminating cellular nuances that have long eluded conventional diagnostic techniques.
The study, recently published in the journal Cyborg and Bionic Systems on March 6, 2025, introduces a sophisticated robotic micromanipulation apparatus that fuses cutting-edge technologies: ODEP, microfluidics, live-cell imaging, and advanced machine learning algorithms. This integrative approach enhances the fidelity and depth of single-cell phenotyping by automating manipulation and analysis processes while exploiting the unique dielectric properties inherent to individual cells.
Characterizing cellular defects, especially those underpinning multifactorial disorders such as reproductive failure, presents a formidable challenge due to the intricate interplay among genetic mutations, environmental influences, and lifestyle factors. Conventional methodologies—ranging from micropipette aspiration and atomic force microscopy to Raman spectroscopy and optical or magnetic tweezers—offer invaluable glimpses into cellular biomechanics and biochemical states. However, these modalities often fall short in temporal or spatial resolution and lack adaptability across diverse experimental conditions.
Optoelectronic tweezers, or ODEP, emerge as a compelling alternative by generating locally nonuniform electric fields through dynamically reconfigurable virtual electrodes projected by patterned light. This mechanism produces significant dielectrophoretic forces at minimal light intensities—ranging from 10⁻² to 10 W/cm²—minimizing photodamage and preserving cellular viability during analysis. The flexibility of light projection permits real-time modulation of electrode patterns, enabling precise, non-contact manipulation of individual cells within microfluidic environments.
The robotic system devised by the research team harnesses these ODEP capabilities to maneuver and position single endometrial stromal cells extracted from patient biopsies. The automated control system not only replicates electrode reconfiguration with high temporal resolution but also dynamically alters electric stimuli characteristics to extract a comprehensive portrait of cell behaviors, including deformation, orientation, and electrokinetic displacement. These phenotypic signatures afford insights into the heterogeneity and physiological status of stromal cells derived from fertile individuals versus those afflicted by recurrent implantation failure (RIF) or unexplained recurrent pregnancy loss (uRPL).
A pivotal aspect of this platform lies in its integration with microfluidics, which provides a highly controlled and laminar flow environment conducive to serial and parallel cell analysis. The microfabrication of lab-on-a-chip devices enables seamless interfacing with live-cell imaging modalities and advanced pattern recognition techniques powered by machine learning. This confluence elevates the precision of single-cell dielectric characterization, permitting discrimination between subtle variations in cell populations that correlate with reproductive outcomes.
The research underscored a distinct dielectric response profile among the endometrial cells sourced from the three patient cohorts. Differences manifested not only in centroid electrokinetics but also in deformation dynamics and orientation under ODEP-induced electric fields. Such multifaceted data, when combined, enhance the analytical granularity, fostering a more nuanced understanding of cellular dysfunctions linked to reproductive pathologies.
In prior literature, ODEP has demonstrated remarkable utility across diverse biological applications, including the manipulation and isolation of antibiotic-resistant bacterial subclones, sorting of circulating tumor cells, early detection of apoptosis, and identification of transcriptomic variations. This study advances the frontier by applying these principles specifically to primary human endometrial stromal cells, thereby laying the foundation for future diagnostic tools that are both highly sensitive and non-invasive.
The collaborative work led by Eugenio Martinelli and Joanna Filippi, among others, represents a significant stride toward automated, high-throughput phenotyping platforms capable of capturing the dynamic and heterogeneous nature of cells implicated in reproductive health. By establishing a clear link between cell dielectric properties and patient reproductive history, this approach opens avenues for personalized medicine strategies tailored to individual cellular profiles.
Looking ahead, the adaptability of the ODEP platform, combined with robotic automation and machine learning, could revolutionize areas beyond reproductive medicine. The versatility in manipulating a broad spectrum of cell types without physical contact or fluorescent labeling heralds a new era in biophysical cell characterization, promising advancements in cancer research, stem cell therapy, and immunology.
This research not only exemplifies the potential of merging physics and engineering with cellular biology but also illustrates how interdisciplinary approaches can address longstanding challenges in disease diagnosis and treatment. As robotic micromanipulation systems evolve, their application in clinical settings may provide clinicians with powerful tools to stratify patients, predict treatment outcomes, and tailor interventions with unprecedented accuracy.
In summary, the development of this ODEP-based robotic system signifies a quantum leap in single-cell analysis technology. It not only surmounts the limitations of existing methodologies but also crafts a comprehensive analytical pipeline that encapsulates micromanipulation, real-time measurement, and sophisticated data interpretation. Its application to endometrial stromal cells marks a landmark step towards deciphering the complex biology of reproductive failure and potentially enhancing patient care through precision diagnostics.
The paper detailing this innovative system—titled “ODEP-Based Robotic System for Micromanipulation and In-Flow Analysis of Primary Cells”—features contributions from a multidisciplinary team: Joanna Filippi, Paola Casti, Valentina Lacconi, Gianni Antonelli, Michele D’Orazio, Giorgia Curci, Carlo Ticconi, Rocco Rago, Massimiliano De Luca, Alessandro Pecora, Arianna Mencattini, Steven L. Neale, Luisa Campagnolo, and Eugenio Martinelli. Their comprehensive investigation provides a compelling proof of principle that sets the stage for future exploration and clinical translation.
As the frontier of biophysical cell analysis expands, innovations like the ODEP-based robotic system will become indispensable for unraveling the nuanced heterogeneity of cells implicated in multifactorial diseases. This synergy of photonics, microfluidics, robotics, and artificial intelligence embodies the future of biomedical research—where devices not only observe but actively interrogate living cells with an unprecedented level of sophistication and clinical relevance.
Subject of Research: Single-cell phenotyping and classification of patient-derived endometrial stromal cells using optically-induced dielectrophoresis-based robotic micromanipulation.
Article Title: ODEP-Based Robotic System for Micromanipulation and In-Flow Analysis of Primary Cells
News Publication Date: March 6, 2025
Web References: DOI: 10.34133/cbsystems.0234
Image Credits: Eugenio Martinelli, Department of Electronic Engineering, University of Rome Tor Vergata
Keywords
Chemical analysis, Image analysis, Environmental methods
