Spark-Cell Spheroids for Optical Cardiac Pacing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The drug development process is inefficient and costly due to inadequate tools for predicting cardiac toxicity, leading to high drug withdrawal rates and increased costs, as existing methods lack scalable and high-throughput solutions for studying human cardiac electrophysiology and drug action.
Innovation Solution
Development of 'spark-cell' spheroids that can be stored, transported, and deployed for optical pacing of cardiac tissue, utilizing genetically modified cells expressing light-gated ion channels or mechanosensitive entities, enabling robotic integration and high-throughput drug testing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional genetic modification of cardiomyocytes is used to enable optical pacing, then optical pacing capability is achieved, but the process is time-consuming and lacks scalability for high-throughput screening
Solution Approach 1:
The patent introduces a mediator cell type (non-cardiomyocyte cells expressing light-gated ion channels) that transfers the optical pacing function to cardiomyocytes without requiring genetic modification of the cardiomyocytes themselves. This intermediary approach enables optical pacing while maintaining simplicity in the primary cell type and improving integration speed.
Solution Approach 2:
The patent segments the optical pacing function into a separate cell population that can be independently prepared, characterized, and then integrated with cardiomyocytes. This segmentation allows parallel processing and high-throughput preparation of the pacing cells, dramatically improving productivity compared to modifying each cardiomyocyte individually.
2Productivity
If existing cardiac toxicity prediction methods are used, then some level of safety assessment is achieved, but the methods lack high-throughput capability and scalability
Solution Approach 1:
The patent creates a universal assay platform using spheroid cell aggregates that can simultaneously serve multiple functions: optical pacing, electrophysiological recording, and drug toxicity screening. This multi-functional platform enables high-throughput screening while maintaining reliable cardiac toxicity prediction through standardized, reproducible spheroid preparations.
Solution Approach 2:
The patent changes the organizational parameter of the cell system from individual cells or simple monolayers to three-dimensional spheroid aggregates. This parameter change improves the physiological relevance for toxicity testing while enabling automated handling and high-throughput screening formats.
3Reliability
If new drug development processes are implemented with comprehensive cardiac testing, then cardiac safety prediction is improved, but the development time and costs increase
Solution Approach 1:
The patent performs preliminary cardiac safety assessment using the spheroid optical pacing assay early in the drug development process, before proceeding to later-stage clinical trials. This preliminary screening identifies potentially toxic compounds early, preventing waste of time and resources on problematic candidates and reducing overall development time.
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
Facilitates faster integration and more efficient acute pacing experiments, reducing the need for genetic modification of cardiomyocytes and allowing for scalable, high-throughput drug testing, thereby improving the prediction of cardiac toxicity and reducing drug development costs.
Implementation Method 1
a first entity capable of translating one or more external stimuli into a local electric field change
Implementation Method 2
a second entity capable of converting photons having a first energy to photons having a second energy
Implementation Method 3
an entity capable of translating one or more external stimuli into a local electric field change
Data Source
AI summary
Embodiments of the instant disclosure relate to compositions and methods of use thereof that allow for faster integration of acute cardiac pacing experiments compared to the direct genetic modification methods currently in use. Embodiments provided herein provide for spheroids that may be stored, transported, and deployed on site to confer optical pacing of cardiac tissue for use in high-throughput functional in vitro screening assays.