Automated Tissue Dissociation System for Single-Cell Integrity
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Solution Overview
Problem
Current methods for preparing single cells or nuclei from solid tissues are labor-intensive, prone to variability, and can alter gene expression due to mechanical and enzymatic stress, limiting the scalability and clinical utility of single-cell sequencing applications.
Innovation Solution
A Sample Processing System that integrates enzymatic and mechanical disruption mechanisms with automated fluidic processes, using cartridges with mechanical and enzymatic dissociation subsystems to produce high-quality single cells or nuclei with minimal stress, enabling standardized and automated sample preparation for bioanalysis and sequencing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If manual mechanical and enzymatic dissociation methods are used to prepare single cells from solid tissues, then cell separation can be achieved, but the process becomes labor-intensive and prone to variability that alters gene expression
Solution Approach 1:
The system segments the tissue dissociation process into distinct functional modules: mechanical disruption chamber, enzymatic treatment chamber, and filtration chamber. Each chamber performs a specific function, allowing standardized processing while reducing variability in gene expression profiles.
Solution Approach 2:
The patent replaces manual mechanical dissociation operations with an automated mechanical disruption system that uses controlled shear forces and shear stress to separate cells from tissue. This substitution eliminates labor-intensive manual manipulation while maintaining cell separation quality and reducing variability.
2Productivity
If intensive mechanical and enzymatic processing is applied to release cells from tissue, then cell yield increases, but gene expression is altered due to cellular stress
Solution Approach 1:
The system applies periodic enzymatic treatment cycles followed by gentle mechanical disruption. This periodic action allows cells to be released progressively without sustained exposure to harsh conditions, maintaining cell yield while minimizing stress-induced gene expression changes.
Solution Approach 2:
The patent controls and optimizes parameters including enzymatic concentration, treatment duration, and mechanical shear stress levels. By precisely adjusting these parameters, the system achieves high cell yield while keeping cellular stress within acceptable ranges to preserve gene expression integrity.
3Reliability
If standardized automated processing is implemented, then variability is reduced and workflow is simplified, but initial system complexity increases
Solution Approach 1:
The automated system is designed with universal components that can process different tissue types through the same standardized protocol. The mechanical disruption chamber, enzymatic treatment system, and filtration apparatus serve multiple functions across various applications, reducing long-term complexity despite initial system complexity.
Solution Approach 2:
The system incorporates automated fluid delivery, timing control, and waste removal mechanisms that operate without continuous human intervention. This self-service capability ensures consistent processing parameters are maintained throughout the dissociation process, improving reliability while the automation handles the complexity.
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
The system simplifies workflows, reduces variability, and preserves the integrity of single cells or nuclei, facilitating high-throughput single-cell sequencing and enabling the production of high-quality samples for bioanalysis and clinical applications.
Implementation Method 1
enzymatic disruption of the tissue to release cells from the tissue
Implementation Method 2
a peristaltic pump to move fluids through the system
Data Source
AI summary
A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues and in some embodiments use the single cells to form organoids or microtissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells and then use a hanging droplet method to form organoids or microtissues.