Acoustic Tissue Dissociation Device for Single-Cell Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing tissue dissociation methods are time-consuming, costly, and require chemicals/enzymes, making them inefficient for preparing complex tissue samples into single cells for direct single cell analysis (SCA).
Innovation Solution
A device and method that utilize a pump for back and forth liquid flow, mechanical features for shear forces, and acoustic energy to dissociate tissue samples into single cells without the need for chemicals or enzymes, allowing for immediate analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional tissue dissociation methods using chemicals/enzymes and mechanical agitation are used, then tissue can be broken down into single cells, but the process becomes time-consuming and costly with multiple manual preparation steps
Solution Approach 1:
The patent replaces traditional mechanical agitation methods (vortexing, plate shaking, centrifugation) with an acoustic field-based dissociation system. Acoustic waves are applied directly to the tissue sample to induce mechanical stress and break down tissue into single cells, eliminating the need for manual mechanical operations and significantly reducing preparation time
Solution Approach 2:
The patent introduces acoustic waves as an intermediary energy form to mediate the dissociation process. Instead of direct mechanical contact or chemical enzymes, acoustic energy serves as the intermediary that transfers mechanical stress to the tissue sample, enabling efficient cell separation without traditional mechanical or chemical agents
2Productivity
If chemical/enzyme-based dissociation media are used, then tissue can be dissociated into single cells, but the cost of reagents and instrumentation increases significantly
Solution Approach 1:
The patent substitutes expensive chemical/enzymatic reagents with an acoustic field-based mechanical dissociation system. The acoustic transducer generates mechanical waves that physically break down tissue, eliminating the need for costly enzymes like collagenase or trypsin and reducing reagent costs to near zero
Solution Approach 2:
The patent employs a simple, inexpensive device architecture where the primary component is an acoustic transducer that can be easily manufactured or replaced. The system avoids expensive instrumentation by using a straightforward acoustic field generation approach, making the dissociation process cost-effective
3Productivity
If multiple manual preparation steps and expensive instrumentation are used, then tissue dissociation can be achieved, but the device complexity and operational difficulty increase
Solution Approach 1:
The patent merges multiple dissociation functions (mechanical stress application, cell separation, and single-cell delivery) into a single integrated acoustic device. The acoustic transducer simultaneously performs tissue breakdown and cell separation without requiring separate instrumentation for each step, simplifying the overall device architecture
Solution Approach 2:
The acoustic field-based device serves multiple functions: it dissociates tissue, separates cells from clumps, and delivers single cells to the analysis platform. This multi-functional approach eliminates the need for multiple specialized instruments and manual操作步骤, reducing operational complexity
4Productivity
If traditional dissociation protocols are used, then single cells can be obtained, but cell viability and integrity may be compromised during lengthy processing
Solution Approach 1:
The patent replaces harsh mechanical agitation and chemical enzyme treatment with gentle acoustic field-based dissociation. The acoustic waves apply controlled mechanical stress that is sufficient to break down tissue but gentle enough to preserve cell membrane integrity and viability, avoiding the damaging effects of traditional methods
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 solution enables rapid and cost-effective preparation of single cells from complex tissue samples, maintaining cell viability and integrity, and facilitating direct single cell analysis without additional processing steps.
Implementation Method 1
an acoustic outlet in fluid communication with the microchannel, connected to an acoustic region comprising a transducer operative to generate acoustic radiation pressure applied to the single cells flowing through the microchannel
Implementation Method 2
a pump capable of providing a back and forth liquid flow including a forward flow and a reverse flow through the device, in combination with one or more mechanical features to provide shear forces
Data Source
AI summary
Described herein are methods and devices directed to preparing complex tissue samples for direct single cell analysis (e.g., scRNAseq) in a comprehensive, enzyme-free manner. The device and method use shear forces, mechanical features, electrical treatment, and acoustics, in addition to programmed microfluidic flow to dissociate a tissue sample into a purified suspension of single cells. In an example, a tissue sample is loaded into a well with retaining mesh on either side. A combination of microfluidic flow, shear, and electrical treatment elutes clumps (e.g., aggregates or agglomerates) of cells from this well, while a sample-specific, back and forth flow is repeated to begin an impurity removal process. At an outlet of the device, purified cells suitable for single cell analysis are eluted. As described herein, the device can be operated continuously.