Gripper Assembly for 3D Living Tissue via Suction and Perfusion
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Solution Overview
Problem
Current bio-printers have limited success in creating complex 3D organ structures due to low cell density, slow throughput, and inability to form thick tissues that require perfusion, and existing pick-and-place instruments are not suitable for use in aqueous environments or precise cell handling.
Innovation Solution
A device and method for assembling aggregations of adherent cells using a gripper and build support within an assembly vessel, allowing for precise placement and perfusion of living microtissue building parts to create thick, high-density 3D tissues layer-by-layer, employing a controllable low-level suction head and perfusate for cell handling and alignment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If bio-printers are used to deposit cells and ECM dropwise, then structures can be fabricated, but the throughput is slow and cell density is low
Solution Approach 1:
The invention segments the tissue construction process into discrete building units (microtissues or spheroids) that can be pre-formed and then assembled. Each building unit contains a high density of cells (e.g., 10^6 cells per unit), and multiple units are stacked to create the final tissue structure. This segmentation allows parallel processing and rapid assembly, dramatically improving throughput while maintaining high cell density.
Solution Approach 2:
The invention performs preliminary actions by pre-forming building units (microtissues or spheroids) with high cell density before the main assembly process. These pre-formed units are prepared in advance with optimal cell arrangements and ECM content, allowing the final construction to proceed rapidly through simple stacking and fusion, rather than building cell-by-cell during the main process.
2Length of stationary object
If passive diffusion is used for nutrient delivery, then simple structures can survive, but thick structures with high cell density cannot be sustained
Solution Approach 1:
The invention segments thick tissues into stacks of thinner building units (e.g., multiple layers of microtissues). Each individual unit remains thin enough for passive diffusion to sustain cells, while the stacked configuration achieves the desired overall thickness. This segmentation maintains cell viability in each layer while building thick composite structures.
Solution Approach 2:
The invention introduces perfusion channels as intermediary structures that run through the stacked building units. These channels deliver nutrients and remove waste products actively, mediating between the external environment and the deep interior of thick tissues. The perfusion system enables sustained viability in thick structures that would otherwise be inaccessible to passive diffusion.
3Productivity
If existing pick-and-place instruments are used, then high throughput can be achieved, but precision and tissue integrity are compromised
Solution Approach 1:
The invention replaces mechanical pick-and-place systems with a fusion-based assembly approach. Building units are positioned using fluid flow control and magnetic fields rather than mechanical grippers, eliminating the risk of mechanical damage. The units are then fused together through controlled cell-cell adhesion and ECM crosslinking, achieving both high precision and high throughput without mechanical intervention.
Solution Approach 2:
The invention introduces ECM and cell adhesion molecules as intermediary substances that mediate the bonding between building units. These intermediaries enable precise positioning and secure attachment without mechanical contact, allowing gentle handling and precise placement while maintaining tissue integrity throughout the assembly process.
4Adaptability or versatility
If simple structures are created with modest thickness, then passive diffusion suffices, but complex thick organs cannot be engineered
Solution Approach 1:
The invention segments complex organs into modular building units that can be independently formed and then assembled into sophisticated 3D structures. Each unit can contain specific cell types and ECM compositions, and stacking these units in various configurations enables the creation of complex organ architectures with controlled thickness, including internal chambers, ducts, and vascular networks.
Solution Approach 2:
The invention introduces perfusion channels and vascular networks as intermediary structures that enable thick, complex organ structures to be sustained. These channels are integrated into the stacked building units and provide active transport of nutrients and waste removal, allowing the engineering of thick organs with high structural complexity that would be impossible with passive diffusion alone.
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
Enables the construction of complex 3D tissues and organs with high cell density and perfusion, overcoming limitations of existing bio-printers and pick-and-place instruments, facilitating the creation of accurate in vitro models for research and reducing animal use in testing.
Implementation Method 1
A controllable low-level suction head is employed to grip living microtissue building parts
Implementation Method 2
directing perfusate across the first aggregation of cells in a direction toward the build membrane and then through to build membrane
Data Source
AI summary
A device for assembling aggregations of adherent cells includes a gripper moveable within an assembly vessel that fixes aggregations of adherent cells at a membrane of the gripper and, by movement of the gripper, assembles aggregations of cells on a separate membrane within the vessel, thereby creating a three-dimensional assembly of aggregations of cells that fuse and can be employed in surgical procedures as a unitary tissue of adherent cells. The aggregations of cells, as assembled, can assume three-dimensional configurations distinct from any one of the component aggregations of cells assembled.