OptoDyCE All-Optical Cardiac Electrophysiology System
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Solution Overview
Problem
Current preclinical testing for cardiac toxicity relies on incomplete predictors like QT prolongation and HERG block, leading to unnecessary drug attrition, and lacks the capability for spatio-temporally dynamic stimulation and simultaneous recording of voltage and calcium relationships, especially for drugs affecting calcium handling.
Innovation Solution
The development of an all-optical dynamic cardiac electrophysiology system, OptoDyCE, which uses optogenetic tools for optical pacing and sensing, enabling high-throughput, contactless, and simultaneous recording of electrophysiological and electromechanical responses in human cardiomyocytes, including intracellular calcium and contractility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional electrical stimulation and recording methods are used, then contact-based measurement is achieved, but scalability and adaptability to different cell lines are limited
Solution Approach 1:
The patent replaces mechanical contact-based electrical stimulation and recording with an all-optical system. Optical stimulation uses light to activate photoreceptive elements in cells, and optical recording uses voltage-sensitive dyes or genetically encoded indicators to detect electrical activity without physical contact. This substitution enables scalability to high-throughput formats and adaptability to various cell lines while eliminating the complexity of maintaining electrical contacts in multi-well formats.
Solution Approach 2:
The patent introduces optical intermediaries (light sources, optical fibers, and photodetectors) as mediators between the stimulation/recording system and the cells. This intermediary optical layer allows non-contact interaction with cells, enabling high-throughput screening formats while maintaining the ability to stimulate and record from diverse cell types without requiring specialized contact infrastructure.
2Measurement precision
If optical readout systems like FLIPR are used, then contactless measurement is achieved, but temporal resolution for tracking voltage changes is insufficient
Solution Approach 1:
The patent optimizes optical recording parameters including using voltage-sensitive dyes with fast response kinetics, adjusting illumination intensity and wavelength, and tuning camera exposure times to achieve high temporal resolution (capable of tracking action potentials at appropriate speeds). These parameter optimizations enable precise temporal measurement of voltage changes while working within the constraints of optical system complexity.
3Adaptability or versatility
If static stimulation methods are used, then simple protocol implementation is achieved, but dynamic testing capabilities are lost
Solution Approach 1:
The patent implements dynamic stimulation protocols through optical control, allowing real-time adjustment of stimulation frequency, duration, and intensity. The optical stimulation system can deliver trains of stimuli, vary pacing rates, and apply complex stimulation patterns that mimic physiological conditions or induce pathological states, enabling dynamic testing capabilities while managing system complexity through software control.
4Loss of information
If comprehensive electrophysiological parameters are recorded simultaneously, then complete cardiotoxicity assessment is achieved, but data complexity and analysis burden increase
Solution Approach 1:
The patent employs a multi-functional optical recording system that simultaneously captures multiple electrophysiological parameters (action potential duration, calcium transients, contractility) using a unified platform. This universal system integrates voltage sensing, calcium imaging, and mechanical measurement capabilities into a single coherent framework, enabling comprehensive cardiotoxicity assessment while managing data complexity through integrated acquisition and analysis software.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
OptoDyCE provides high-content, high-throughput data on drug effects, improving the prediction of cardiotoxicity and reducing the risk of arrhythmias by enabling dynamic and spatially resolved measurements of cardiac responses, thus constraining computational models and facilitating more accurate drug testing.
Implementation Method 1
The first wavelength was selected to excite a voltage-sensitive dye (e.g., Di-4-ANBDQBS) and the second wavelength was selected to detect fluorescence emission from the voltage-sensitive dye
Implementation Method 2
The first wavelength was selected to excite a calcium-sensitive dye (e.g., Rhod-4, AM) and the second wavelength was selected to detect fluorescence emission from the calcium-sensitive dye
Data Source
AI summary
Bio-photonic devices or target cells and cell cultures including bio-photonic devices and target cells are provided. Methods of preparing cell cultures including bio-photonic devices and target cells are also provided. Methods of analyzing the electrophysiology of target cells using the cell cultures are provided. Systems for analyzing the electrophysiology of target cells are also provided.