Bei dieser Technologie handelt es sich um eine integrierte, dreimodale Plattform, die gleichzeitig die Kalziumdynamik, die elektrischen Feldpotenziale sowie die Kontraktionskraft und -länge in künstlichem Herzmuskel in einem einzigen Aufbau erfasst. Mithilfe einer speziellen Korrelationseinheit, die gemeinsame Zeitmarker in alle Kanäle einspeist, ermöglicht das System eine zeitliche Abstimmung im Submillisekundenbereich, ereignisbasierte Analysen und eine effiziente Datenverarbeitung. Damit eignet es sich für hochdurchsatzfähige Herzmedikamententests und die Modellierung von Herzerkrankungen.
Synchronisierte Multiparameter-Messung kontraktiler Herzgewebe für das Wirkstoff-Screening
Challenge
Many current cardiac in vitro platforms focus on only one functional readout, such as calcium imaging, MEA recordings or contractility, or they combine methods that interfere with each other and complicate data correlation. This limits the ability to quantitatively link excitation, calcium handling and force generation, especially under complex stimulation protocols or disease‑like conditions that are increasingly required by pharma and regulatory stakeholders.
Our Solution
The invention provides a method and device in which an engineered cardiac tissue construct is suspended between at least two movable holding elements inside a culture medium–filled measurement chamber. Three coordinated measurement units are integrated in a geometry that maintains access for all modalities:
- A fluorescence microscope records spatially and temporally resolved calcium‑dependent fluorescence (chemical potential) in a defined region of the tissue.
- A microelectrode array (MEA), gently positioned from above, measures the time‑resolved distribution of electrical field potentials in a second region that at least partially overlaps in projection with the optical field of view.
- A force/length measurement system detects the distance between the holding elements and/or the tensile force exerted by the tissue, with the option to actively modulate length and preload via an actuator.
All three signal streams are connected to a correlation unit that inserts common or synchronized time markers, so that the calcium, electrical and mechanical traces can be aligned with sub‑millisecond precision and stored as multichannel data. The system supports programmable mechanical loading and electrical stimulation patterns, enabling the imposition or training of defined physiological or pathological dynamic states before and during exposure to candidate drugs or other interventions.
Advantages
- Three‑modal synchronized readout: Simultaneous, time‑marker–based correlation of calcium transients, electrical field potentials and force/length signals in the same cardiac construct.
- Event‑focused and efficient data handling: Time markers allow selection of relevant time windows around defined events, substantially reducing data volume while preserving rich multiparametric information.
- Robust analysis and failure tolerance: Redundant, multimodal data mitigate artefacts or dropouts in individual channels and support more reliable characterization of excitation–contraction coupling.
- Programmable mechanical and electrical conditioning: Adjustable preload, stretch and pacing protocols permit the generation of physiological and disease‑like dynamic states in engineered heart tissue.
- Suitable for translational workflows: Integrates into preclinical pipelines that require high‑content, dose‑ and time‑dependent assessment of cardiac drug effects in human‑relevant models.
Applications
- Suitable for translational workflows: Integrates into preclinical pipelines that require high‑content, dose‑ and time‑dependent assessment of cardiac drug effects in human‑relevant models.
- In vitro modeling and quantification of cardiomyopathies, arrhythmias and other cardiac pathologies by applying disease‑relevant mechanical and electrical loading schemes.
- Optimization, maturation and quality control of engineered heart muscle constructs and cardiac implants under defined mechanical and electrical conditioning.
- Comparative testing of multiple compounds or treatment regimens under identical, well‑defined dynamic states across parallel tissue samples.
Development Status
A prototype system and method have been established for engineered cardiac tissue constructs.
Patent Status
After a German priority patent application an international PCT patent application has been filed (Applicant: Georg-August-Universität Göttingen, Universitätsmedizin).
Kontakt
- Dr. Stefan Uhle
- Patent & Innovation Manager Biotechnology
- suhle@sciencebridge.de
- +49 551 30724 154
- BioC-2527-UMG
